Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria.

The gastrointestinal tract represents one of the largest body surfaces that is exposed to the outside world. It is the only mucosal surface that is required to simultaneously recognize and defend against pathogens, while allowing nutrients containing foreign antigens to be tolerated and absorbed. It differentiates between these foreign substances through a complex system of pattern recognition receptors expressed on the surface of the intestinal epithelial cells as well as the underlying immune cells.

Role of Bone Marrow Maturity, Insulin-Like Growth Factor 1 Receptor, and Forkhead Box Protein N1 in Thymic Involution and Rejuvenation.

Thymic involution is associated with age-related changes of the immune system. Utilizing our innovative technique of transplantation of a thymus as an isolated vascularized graft in MHC-inbred miniature swine, we have previously demonstrated that aged thymi are rejuvenated after transplantation into juvenile swine. Here we have studied the role of insulin-like growth factor (IGF) and forkhead-box protein-N1 (FOXN1) as well as bone marrow (BM) in thymic rejuvenation and involution.

Adoptive Transfer of Renal Allograft Tolerance in a Large Animal Model.

Our recent studies in an inbred swine model demonstrated that both peripheral and intra-graft regulatory cells were required for the adoptive transfer of tolerance to a second, naïve donor-matched kidney. Here, we have asked whether both peripheral and intra-graft regulatory elements are required for adoptive transfer of tolerance when only a long-term tolerant (LTT) kidney is transplanted. Nine highly-inbred swine underwent a tolerance-inducing regimen to prepare LTT kidney grafts which were then transplanted to histocompatible recipients, with or without the peripheral cell populations required for adoptive transfer of tolerance to a naïve kidney.

High incidence of xenogenic bone marrow engraftment in pig-to-baboon intra-bone bone marrow transplantation.

Previous attempts of α-1,3-galactocyltransferase knockout (GalTKO) pig bone marrow (BM) transplantation (Tx) into baboons have demonstrated a loss of macro-chimerism within 24 h in most cases. In order to achieve improved engraftment with persistence of peripheral chimerism, we have developed a new strategy of intra-bone BM (IBBM) Tx. Six baboons received GalTKO BM cells, with one-half of the cells transplanted into the bilateral tibiae directly and the remaining cells injected intravenously (IBBM/BM-Tx) with a conditioning immunosuppressive regimen.

Porcine cytomegalovirus infection is associated with early rejection of kidney grafts in a pig to baboon xenotransplantation model.

Background: Recent survivals of our pig-to-baboon kidney xenotransplants have been markedly shorter than the graft survivals we previously reported. The discovery of high levels of porcine cytomegalovirus (pCMV) in one of the rejected xenografts led us to evaluate whether this reduction in graft survival might be because of the inadvertent introduction of pCMV into our α1,3-galactosyltransferase gene knockout swine herd.

Methods: Archived frozen sections of xeno-kidney grafts over the past 10 years were analyzed for the presence of pCMV, using real-time polymerase chain reaction.

The rejuvenating effects of leuprolide acetate on the aged baboon's thymus.

Background: We have previously demonstrated that the juvenile thymus plays an essential role in tolerance induced by both renal transplantation and a short course of calcineurin inhibitors. Aged thymi have a decreased ability to induce tolerance. Luteinizing hormone-releasing hormone (LHRH) is known to pharmacologically rejuvenate the thymus in rodents.

Abrogation of renal allograft tolerance in MGH miniature swine: the role of intra-graft and peripheral factors in long-term tolerance.

We have previously demonstrated that long-term tolerance (LTT) of an MHC class-I mismatched renal allograft can be achieved with a short course of cyclosporine. In order to examine regulatory mechanisms underlying tolerance in this model, we assessed the contributions of factors within the graft and in the peripheral blood for their relative roles in the maintenance of stable tolerance. Twelve LTT recipients of MHC class-I mismatched primary kidneys were subjected to a treatment consisting of donor-specific transfusion followed by leukapheresis, in order to remove peripheral leukocytes, including putative regulatory T cells (Tregs).

Increased levels of anti-non-Gal IgG following pig-to-baboon bone marrow transplantation correlate with failure of engraftment.

Background: The development of genetically modified pigs, which lack the expression of alpha 1-3 galactosyl transferase, (GalT-KO pigs) has facilitated the xenogeneic transplantation of porcine organs and tissues into primates by avoiding hyperacute rejection due to pre-existing antibodies against the Gal epitope. However, antibodies against other antigens (anti-non-Gal antibodies), are found at varying levels in the pre-transplant sera of most primates. We have previously found that baboons with high levels of pre-transplant anti-non-Gal IgG, conditioned with a non-myeloablative conditioning regimen, failed to engraft following pig-to-baboon bone marrow transplantation (Xenotransplantation, 17, 2010 and 300).

Vascularized composite allograft transplant survival in miniature swine: is MHC tolerance sufficient for acceptance of epidermis?

Background: We have previously reported that Massachusetts General Hospital miniature swine, which had accepted class I-mismatched kidneys long-term after 12 days of high-dose cyclosporine A, uniformly accepted donor-major histocompatibility complex (MHC)-matched kidneys without immunosuppression but rejected donor MHC-matched split-thickness skin grafts by day 25, without changes in renal graft function or antidonor in vitro responses. We have now tested whether this "split tolerance" would also be observed for the primarily vascularized skin of vascularized composite allografts (VCAs).

Methods: Group 1 animals (n=3) received donor MHC-matched VCAs less than 70 days after primary kidney transplant (KTx).

Iatrogenic subfoveal diamond particle after macular hole repair surgery.

Purpose: To discuss surgical options and visual outcome when faced with a diamond intraoperative foreign body during macular hole surgery.

Methods: Case study of an iatrogenic in-the-macular-hole diamond particle noted during macular hole surgery. No attempt to retrieve the diamond from the macular hole was made during surgery.

The induction of tolerance of renal allografts by adoptive transfer in miniature swine.

Our previous in vitro data have demonstrated that regulatory mechanisms are involved in tolerance of class I-mismatched renal allografts in miniature swine treated with 12 days of high dose Cyclsporin A. In this study, we attempted to induce tolerance of class I-mismatched kidneys by adoptive transfer of cells and/or kidneys from long-term tolerant animals. Fifteen SLA(dd) miniature swine received 1.

Vitreous hemorrhage after whole-body vibration training.

Purpose: The purpose of this study was to describe spontaneous vitreous hemorrhage after a session of whole-body vibration training.

Method: This is a case report of a 52-year-old man with no ophthalmic history who presented with a uniocular drop in vision.

Results: Examination showed two areas of vitreous condensations associated with vitreous hemorrhage.

Capsule contraction syndrome with haptic deformation and flexion.

We report a case series of capsule contraction syndrome in 5 eyes of 4 patients and describe a previously unreported complication: full flexion of the haptics onto the anterior surface of the optic. Haptics have been reported to slide anterior to the optic while remaining in their original coronal plane. As surgeons move to the use of preloaded injectable IOLs, it is important to scrutinize haptic-optic junction design and IOL material in the light of this complication.

Effect of a total smoking ban in a maximum security psychiatric hospital.

An archival study was performed in a maximum security forensic hospital to evaluate the effects of a total ban on smoking and all tobacco products. One hundred and forty patients were characterized as nonsmokers or light, moderate or heavy smokers. Patient records for the four weeks prior to the ban were compared with their records for the four weeks subsequent to the ban.

Incidence of blindness due to diabetic eye disease in Fife 1990-9.

Aims: In the light of goals for reducing blindness due to diabetes, published in the St Vincent Declaration, 1989, the aim of this study was to find the incidence and prevalence of blindness in the diabetic population of Fife.

Methods: All blind registrations for the period 1990-9 were studied. Those with diabetes as the first or main diagnosis were included as new diabetic blind.

Quantitative structure-activity relationship (QSAR) analysis of surfactants influencing attachment of a Mycobacterium sp. to cellulose acetate and aromatic polyamide reverse osmosis membranes.

A series of 23 neutral, anionic, and zwitterionic surfactants were tested at a concentration of 0.1% wt/vol for their influence on attachment of a Mycobacterium sp. to cellulose acetate (CA) and polyamide (PA) reverse osmosis (RO) membranes.