Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants

BACKGROUND: Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. METHODS: Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. RESULTS: Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. CONCLUSION: Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.     

Glucagon-like peptide I enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas

OBJECTIVE: To investigate the acute effects of glibenclamide and glucagon-like peptide I (GLP-I) and their combination in perfused isolated rat pancreas and in patients with secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: Rat islets were perfused with 10 nmol/l GLP-I in combination with 2 mumol/l glibenclamide. In human experiments, GLP-I (0.75 pmol. kg-1.min-1) was given as a continuous infusion during 240 min, while glibenclamide (3.5 mg) was administered orally. Eight patients participated in the study (age 57.6 +/- 2.7 years, BMI 28.7 +/- 1.5 kg/m2, mean +/- SE). In all subjects, blood glucose was first normalized by insulin infusion administered by an artificial pancreas (Biostator). RESULTS: GLP-I increased the insulinotropic effect of glibenclamide fourfold in the perfused rat pancreas. In human experiments, treatment with GLP-I alone and in combination with glibenclamide significantly decreased basal glucose levels (5.1 +/- 0.4 and 4.5 +/- 0.1 vs. 6.0 +/- 0.3 mmol/l, P < 0.01), while with only glibenclamide, glucose concentrations remained unchanged. GLP-I markedly decreased total integrated glucose response to the meal (353 +/- 60 vs. 724 +/- 91 mmol.l-1. min-1, area under the curve [AUC] [-30-180 min], P < 0.02), whereas glibenclamide had no effect (598 +/- 101 mmol.l-1. min-1, AUC [-30-180 min], NS). The combined treatment further enhanced the glucose lowering effect of GLP-I (138 +/- 24 mmol. l-1.min, AUC [-30-180 min], P < 0.001). GLP-I, glibenclamide, and combined treat-stimulated meal-induced insulin release as reflected by insulinogenic indexes (control 1.44 +/- 0.4; GLP-I 6.3 +/- 1.6, P < 0.01; glibenclamide 6.8 +/- 2.1, P < 0.01; combination 20.7 +/- 5.0, P < 0.001). GLP-I inhibited basal but not postprandial glucagon responses. Using paracetamol as a marker for gastric emptying rate of the test meal, treatment with GLP-I decreased gastric emptying at 180 min by approximately 50% compared with the control subjects (P < 0.01). CONCLUSIONS: In acute experiments on overweight patients with NIDDM, GLP-I exerted a marked antidiabetogenic action on the basal and postprandial state. The peptide stimulated insulin, suppressed basal glucagon release, and prolonged gastric emptying. The glucose-lowering effect of GLP-I was further enhanced by glibenclamide. This action may be at least partially accounted for by a synergistic effect of these two compounds on insulin release. Glibenclamide per se enhanced postprandial but not basal insulin release and exerted a less pronounced antidiabetogenic effect compared with GLP-I.     

Constraint Databases: Promising Technology or Just Intellectual Exercise?

This paper describes the state of Constraint Databases (CDBs), a young discipline at the intersection of Database Management, Constraint Programming, Computational Geometry and Operations Research. As in Constraint Logic Programming, constraints in CDBs are a first class data type, and can play many modeling roles including spatial and temporal behavior, complex design requirements, and partial and incomplete information, for which existing databases have proven inadequate. We motivate the importance of CDBs, outline the work in the area that has been done, the current trends, and future directions and challenges. We briefly discuss (1) constraint modeling, canonical forms and algebras, (2) data models and query languages, (3) indexing and approximation-based filtering, (4) constraint algebra algorithms and global optimization, and (5) systems and case studies. We argue that CDBs are a promising technology that will impact many important application realms, and furthermore have the potential to be integrated into future database systems, and operations research and constraint programming tools.     

A Skeleton-based Approach for Detection of Perceptually Salient Features on Polygonal Surfaces

The paper presents a skeleton‐based approach for robust detection of perceptually salient shape features. Given ashape approximated by a polygonal surface, its skeleton is extracted using a three‐dimensional Voronoi diagramtechnique proposed recently by Amenta et al. [ 3 ]. Shape creases, ridges and ravines, are detected as curvescorresponding to skeletal edges. Salient shape regions are extracted via skeleton decomposition into patches.The approach explores the singularity theory for ridge and ravine detection, combines several filtering methodsfor skeleton denoising and for selecting perceptually important ridges and ravines, and uses a topological analysisof the skeleton for detection of salient shape regions. ACM CSS: I.3.5 Computational Geometry and Object Modeling     

New Technology for Producing Molybdenum Wire Billets

On the basis of systematic studies of intense methods for metal forming, a production scheme has been developed, substantiated by experiment and realized for manufacturing molybdenum wire. The main stages are helical rolling of small rounded bars, vibratory drawing with induction heating of wire billets, and cold wire drawing with hydrodynamic introduction of lubricant and application to the tool of vibration in the transitional stages of the process (start-up, speed-up, slow-down, and stopping the pulling tool drive).     

Numerical modeling of near corona wire electrohydrodynamic flow in a wire-plate electrostatic precipitator

Numerical modelling of the flow velocity fields for the near corona wire electrohydrodynamic (EHD) flow was conducted. Solutions of the steady, two-dimensional momentum equations have been computed for a wire-plate type electrostatic precipitator (ESP). The equations were solved in the conservative finite-difference form on a fine uniform rectilinear grid of sufficient resolution to accurately capture the momentum boundary layers. The numerical procedure for the differential equations was used by SIMPLEST algorithm. The CFD code coupled with Poisson's electric field, ion transport equations and the momentum equation with electric body force, was used for the numerical simulation with the Chen-Kim k-epsiv turbulent model. The numerical results show that EHD secondary flow was clearly visible in the downstream regions of the corona wire despite the low Reynolds number for the electrode (Re _cw=12.4). Secondary flow vortices caused by the EHD increases with increasing discharge current or EHD number, hence pressure drop of ESP increases     

Isolation of the acidic and basic lectins from winged bean seed (Psophocarpus tetragonolobus (L.) DC)

The acidic and basic lectins of the winged bean were isolated from seed extracts by affinity chromatography on lactose-Sepharose 6B and melibiose Bio-Gel P150, respectively. The lectins isolated from six varieties of Psophocarpus tetragonolobus, collected from different regions of south-east Asia, showed no significant differences in their properties; their subunit M_r and amino acid compositions were the same as those of the acidic and basic lectins isolated by non-affinity methods. On isoelectric focusing the affinity purified acidic lectins showed two major protein components (isolectins) while the affinity purified basic lectins had four protein components. The acidic lectins showed a preference for β-D-galactosides and they agglutinated trypsinised human type A, B and O erythrocytes but not trypsinised rabbit erythrocytes. The basic lectins showed a preference for α-D-galactosides and they agglutinated trypsinised rabbit and human type A and B erythrocytes but not trypsinised human type O erythrocytes.     

Contact melting inside an elastic capsule

An approximate mathematical model of contact melting of an unfixed material in elastic cylindrical and spherical capsules is developed. Since the density of the solid is higher than that of the melt, the melting solid resides at the bottom supported by a thin layer of the generated, convecting, melt, and the capsule swells. The main characteristic scales and non-dimensional parameters, which describe the principal features of the melting process and the liquid flow, are found. Linearisation with regard to the Stefan number as well as the small difference between the densities of the solid and liquid enables us to derive a closed-form evolution equation for the motion of the solid, which also determines the melting rate. Numerical solution of the evolution equation shows that the swelling of the capsule during melting, which is caused by the decrease of the density during phase transition, leads to slowing down of the melting process. This effect is due to flattening of the lower surface of the capsule, which entails fall of the pressure along with thickening of the molten layer. The latter determines the decrease of the melting rate.