Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model

Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or both. To investigate the mechanisms of graft rejection, we have developed a canine model of marrow transplantation, which uses DLA-nonidentical unrelated donors in the absence of postgrafting immunosuppression. In this model most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can be facilitated when the recipients are pretreated with monoclonal antibody (MoAb) S5, which recognizes CD44. In this report, we extended these observations by first cloning the canine CD44 and, next, mapping the epitope recognized by S5, which was located in a region conserved among human and canine CD44 and was distinct from the hyaluronan binding domain. However, in vitro binding of S5 caused a conformational change in CD44, which allowed increased hyaluronan binding. Then, we reexamined the in vivo model of marrow transplantation and compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The enhanced in vivo effect was not related to differences in the MoAbs' avidities, since both S5 and IM7 had equivalent binding to CD44, but most likely related to the specific epitope that S5 recognizes. Thus, this study shows that the effect of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one cannot assume that any anti-CD44 would work.     

Impact of managed care on employment and training: A primer for survival.

Managed care has become the dominant economic force in health care delivery and has challenged many of professional psychology's training concepts and cherished attitudes. Organized psychology has not kept pace with the rapid industrialization of health care during the past decade and has been overlooked as a participant in health economic decisions. A number of changes need to be made in professional education and training if psychology is to be a major player in the new health systems. Additionally, professional psychologists must reexamine some of their most generally accepted attitudes and beliefs if they are to survive. These are described with a number of recommendations for the survival of an embattled profession. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Laser prostatectomy: initial experience and urodynamic follow-up

OBJECTIVES: An evolving technology for the treatment of bladder outlet obstruction due to benign prostatic hyperplasia (BPH) is the use of the side-firing neodymium: yttrium-aluminum-garnet (Nd:YAG) laser to achieve prostatic tissue ablation. The purpose of this study was to determine the short-term efficacy of this procedure in both an objective and subjective manner. METHODS: We examined this technique by carefully evaluating our first 25 men undergoing the procedure. Each patient was subjected to careful symptom score analysis using the American Urological Association symptom index and multichannel urodynamics, including pressure-flow studies both preoperatively and at 3 months postoperatively. RESULTS: At the 3-month follow-up, symptom scores improved from a preoperative mean of 11.4 to 7.2 and the mean maximum flow rate improved from 6.1 to 14.5 cc/s. These are both significant at P < 0.001. Statistically similar improvement was seen in detrusor pressure at opening and at maximum flow. Eighty percent of the men studied had at least a 50% reduction in symptom score and a 50% improvement in flow rate. CONCLUSIONS: We conclude that laser prostatectomy is a promising minimally invasive treatment for bladder outlet obstruction secondary to BPH and deserves further evaluation at longer terms of follow-up.     

Neuropsychiatric aspects of progressive supranuclear palsy

Administering the Neuropsychiatric Inventory (NPI), we examined the behavioral symptoms of 22 patients with progressive supranuclear palsy (PSP), 50 patients with Alzheimer's disease, and 40 controls. PSP patients exhibited apathy (91%), disinhibition (36%), dysphoria (18%) and anxiety (18%), but rarely (< 9%) irritability, abnormal motor behaviors, or agitation. Apathy in PSP was significantly associated with executive dysfunction. The presence of high apathy and low agitation and anxiety scale scores correctly identified the PSP patients 85% of the time. Evaluating the behavioral abnormalities of patients with neurodegenerative disorders will aid diagnosis and facilitate management.     

Laboratory evaluation of the XR-Bond Dentin/Enamel Bonding System

The shear bond strengths of the XR-Bonding System used in conjunction with Herculite composite, to the dentine of forty extracted human permanent first and second molars were determined after the test specimens were stored in physiological saline at 37 degrees C for 48 hours, one week, two weeks and four weeks, respectively. A shear load was applied to the base of the bonded composite cylinders with a knife-edged rod at a crosshead speed of 0.5 mm/minute. The shear bond strengths were expressed in megapascals (MPa). The quantitative microleakage of Class V preparations in dentine (cementum) in forty-eight extracted human maxillary permanent canines restored with the same dentinal bonding system and after storage in physiological saline at 37 degrees C for the same time intervals as for the shear bond strength tests, was determined. On the final day of each time interval the teeth were thermocycled X 500 in a 2 per cent methylene blue solution between 8 degrees C and 50 degrees C with a dwell time of 15 seconds. Microleakage was determined by a spectrophotometric dye-recovery method and expressed in microgram dye/restoration. There was a significant trend for the shear bond strengths to increase with duration of storage (p = 0.01) but the quantitative microleakage was not significantly different (p = 0.75).     

Restoration of T cell-independent type 2 induction of Ig secretion by neonatal B cells in vitro

The humoral immune response of neonates to T cell-independent type 2 (TI-2) Ags is markedly defective. We previously demonstrated that multivalent membrane Ig cross-linking, using dextran-conjugated anti-Ig Abs (anti-Ig-dextran), is an in vitro model for membrane Ig-dependent TI-2 induction of Ig secretion. In this work, we demonstrate that highly purified neonatal B cells are intrinsically defective in IgM secretion in response to anti-Ig-dextran and cytokines in vitro, as well as other modes of B cell activation, relative to adult B cells. However, costimulation of anti-Ig-dextran-activated neonatal B cells with either CD40-ligand, a recombinant bacterial lipoprotein, or LPS restores the IgM secretory response of neonatal B cells to adult levels. Analysis of Ig isotype secretion indicates that neonatal B cells have an enhanced capacity to secrete IgE and IgA relative to other Ig isotypes. These data suggest that neonatal B cells are competent to secrete Ig in response to TI-2 Ags if adequate costimuli are provided, and thus may have particular relevance for the design of vaccine strategies in the immunodeficient host. The data also suggest that neonatal B cells are programmed to secrete relatively enhanced amounts of IgE and IgA, which may be relevant for antimicrobial resistance at mucosal surfaces.     

Visualization of plasma turbulence

We have developed a three-dimensional toroidal gyrokinetic particle simulation to study tokamak turbulence. The gyrokinetic equations are a reduced set derived from the Vlasov-Maxwell equations by phase averaging over the ion gyromotion and keeping only the time and space scales relevant for describing tokamak plasmas. These large-scale simulations in complex geometry can produce gigabytes of data consisting of large 3D arrays evolving in time. Visualization plays a critical role in going from the raw nonlinear solution of these complex equations to a simplified theoretical model explaining the essential underlying physics