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Purpose: After successful treatment of cancers in childhood, the occurrence of second malignant neoplasm (SMN) came to the fore. Few studies have considered the relationship between the radiation dose received and the risk of developing an SMN. To take into account the heterogeneity of the dose distribution so as to evaluate the overall risk of an SMN after a childhood cancer, we therefore focused on the integral dose restricted to the irradiated fields., Methods and Materials: The study was performed in a cohort of 4,401 patients who were 3-year survivors of all types of childhood cancer treated between 1947 and 1986 in France and Great Britain. For each patient, the integral dose was estimated for the volume inside the beam edges., Results: We found a significant dose-response relationship between the overall risk of an SMN and the estimated integral dose. The excess relative risk for each incremental unit of the integral dose was only 0.008 in a linear model and 0.017 when a negative exponential term was considered, when adjusted for chemotherapy. The risk of SMN occurrence was 2.6 times higher in the case of irradiation. However among patients who had received radiotherapy, only those who had received the highest integral dose actually had a higher risk., Conclusions: The integral dose in our study cannot be considered as a good predictor of later risks. However other studies with the same study design are obviously needed to evaluate the use of the integral dose as a tool for decision making concerning different radiotherapy techniques.

The main mode of failure of the acetabular component in total hip arthroplasty is aseptic loosening. Successive generations of cementation techniques have evolved to alleviate this problem. This paper evaluates one such method, Negative Pressure Intrusion Cementation. Two groups of machined bovine cancellous bone samples were created; experimental (n = 26) and control (n = 26). The experimental group was cemented using the negative pressure technique and the control group was cemented in the absence of negative pressure. The relative cement intrusion depths were then assessed for each group using MicroCT. These samples were then further machined and tested to failure in torsion to estimate their mechanical properties. Results show mean cement intrusion depth for the negative pressure group to be 8,676 microm and 6,042 microm for the control group (p = 0.078). Mechanical testing revealed a greater mean torque in the negative pressure group (1.6223 Nm versus 1.2063 Nm) (p = 0.095). This work quantifies the effect of negative intraosseous pressure on cement intrusion depth in cancellous bone and for the first time relates this to increased mechanical strength.

Libraries of mixed-metal hydride materials are synthesized on a silicon microfabricated array of "hot-plate" MEMS devices, which allow high-throughput screening using temperature programmed desorption and infrared thermography. The heating plate of the MEMS device is a membrane with low heat capacity, allowing fast and localized temperature control and the extraction of calorimetric data from thermography. The combination of the synthetic method and screening chip allows a fast determination of the desorption temperature and hydrogen content of the materials. Mixed metal hydrides are synthesized directly. The potential of the method is exemplified by presenting results for the sorption properties of Mg xNi 1- x hydride thin-film materials. The results are consistent with the literature, showing the highest hydrogen capacity and desorption temperature for the MgH 2 phase in Mg-rich compositions and the promotion of a lower temperature desorption from the Mg 2NiH 4 phase, with a concomitant reduction in hydrogen capacity.

The aim of this study was to identify the clinical factors associated with the need for peri-operative blood transfusion in non-anaemic patients undergoing hip or knee arthroplasty. We prospectively evaluated 162 consecutive patients who underwent total hip or knee arthroplasty. Analysis was performed to establish the relationship between all independent variables and the need for postoperative transfusion. Univariate analysis revealed a significant relationship between the need for postoperative blood transfusion and the pre-operative haemoglobin levels (P= 0.001), weight (P= 0.019) and age (P= 0.018). Multivariate analysis identified a significant relationship only between the need for transfusion and the pre-operative haemoglobin level (P= 0.0001). The pre-operative haemoglobin level of the patient was the only variable to independently predict the need for blood transfusion after primary hip or knee arthroplasty.

Aim: To analyze the results of a systematic survey of biological tests in a symptomatic pediatric population consulting for the exploration of a possible food allergy., Patients and Methods: 406 children included in this study, mean age 3.3+3.2 years (2 months-16 years), 159 girls and 247 boys, had cutaneous tests (Stallergènes, Paris, France), assaying of total and specific IgE, and RAST Fx5 (Pharmacia & Upjohn Diagnostics AB, Uppsala, Sweden). Those children suffering from eczema (34.9%), digestive disorders (26.1%), ORL and pulmonary (8.3%), anaphylactic choc (3.4%) or mixed symptoms (27.3%)., Results: The overall positivity of cutaneous tests, all confused age periods, was 34.1% with the following order: egg white (52%, p < 0.05 vs. other food), peanut (46%), egg yolk (42%), fish (34%), wheat (33%), soy (32%), cow's milk (24%) and rice (17%). It decreased significantly with age only for the egg white, 61% (0-1 year) and 68% (1-2 years) vs 31% (> 6 years), p < 0.05. The positivity of cutaneous tests for egg and peanut was more frequent with eczema than with digestive manifestations (64% vs. 44%, 57.6% vs. 34% and 56% vs. 38.7%, p < 0.05). The title of total IgE increased with age, r 0.5 p 0.001. The positivity of specific food IgE was more frequent at 4-6 years (68%) than at 0-1 year (36%), p < 0.05. It revealed, all confused age periods, the following order: egg white (74%) and peanut (64%), p < 0.05 vs. other food, cow's milk (59%), wheat (55%), soy (45%) and fish (24%). The number of high specific food IgE titers was significantly higher than the number of positive cutaneous tests by order of frequency; egg white, peanut, cow's milk, wheat and soy, p < 0.05; the reverse was observed for fish, p < 0.05. Percentage of subjects combining a high title of specific food IgE and a positive cutaneous test for egg white (39.4%) was significantly higher than the percentage of those combining a high RAST Fx5 title and a positive cutaneous test for at least one of 6 corresponding foods (25.2%), p < 0.05., Conclusion: The positivity of different food cutaneous tests, the rate of total and specific IgE titers and the agreement of the results varied according to age, food and symptoms.

Hydrogen peroxide has been used for decades as an effervescent haemostatic agent in arthroplasty. Recently it has been shown to adversely affect the material properties of PMMA. We aim to assess whether any such deleterious effects are demonstrated in an experimental model which mimics the clinical use of hydrogen peroxide. Matched pairs of cancellous bone samples were treated with a swab soaked in either saline or a 3% solution of hydrogen peroxide, prior to manufacture of cement-bone constructs using Palacos or Simplex cement. Thirty pairs were then compared by subjecting them to a torsional shear force until failure and a further thirty pairs were tested to failure in tension. There was no significant difference between the mean torques to failure for the Palacos-peroxide group versus the Palacos-saline group, or the Simplex-peroxide versus the Simplex-saline group (p=0.31 and 0.71 respectively). Similarly there was no significant difference between the mean tension loads to failure for the Palacos-peroxide group versus the Palacos-saline group, and the Simplex-peroxide versus the Simplex-saline group (p=0.79 and 0.23 respectively). We conclude that the use of hydrogen peroxide as an effervescent haemostatic agent has no detrimental effect on the mechanical integrity of the bone-cement interface when compared to normal saline.

Multiple ligament injuries of the canine and feline stifle joint which result in luxation are uncommon. Two cats and one dog, that had sustained such a joint injury were surgically treated. A rupture of the cranial and caudal cruciate ligaments, and at least one collateral ligament was observed in all of the three animals. Prosthetic reconstruction was used, as previously described, in combination with a novel technique of intraoperative placement of a temporary trans-articular pin (TTP) to maintain intra-operative anatomical reduction. TTP placement facilitated maintenance of joint alignment during surgical reconstruction and aided appropriate tensioning of the prosthetic sutures, preventing collapse of femorotibial joint compartments. The TTP was removed prior to closure of the joint allowing immediate post-operative joint mobilisation. Based on assessment by their owners, all the animals made a complete recovery. TTP was considered a relatively simple and effective adjunctive aid for surgical treatment of traumatic luxation of the stifle joint.

A high-throughput method for physical vapor deposition has been applied to the synthesis of libraries of supported gold particles on amorphous substoichiometric TiO(x)() and carbon supports. The TiO(x)() substrate stoichiometry can be varied or kept constant across a supporting sample, and subsequent deposition of particle sizes on supports are controlled through the nucleation and growth process. TEM measurements indicate nucleation and growth of Au particles takes place, with the smallest particles initially observed at 1.4 nm with a maximum density of 5.5 x 10(12) cm(-2) on titania, and 2.6 nm with concomitantly lower density on carbon. The 1.4-nm particles on titania exhibit a binding energy shift in the Au(4f) core level of 0.3 eV from bulk gold, and the shift is approximately 0.1 eV by the time particles grow to a mean size of 2.5 nm. These shifts are associated with final state effects, and the supported gold particles are metallic and appear to be relatively stable in air. When combined with appropriate substrates and screening techniques, this method provides a highly controllable method for the high-throughput synthesis of model supported catalyst.

A novel high-throughput technique has been developed for the investigation of the influence of supported metal particle size and the support on electrocatalytic activity. Arrays with a gradation of catalyst particle sizes are fabricated in a physical vapor deposition system that also allows selection of the support material. Simultaneous electrochemical measurements at all electrodes in the array, together with determination of the actual particle size distribution on each of the electrodes by transmission electron microscopy (TEM), then allows rapid determination of the activity as a function of catalyst center size. The procedure is illustrated using data for the reduction of oxygen on gold nanoparticles supported on both substoichiometric titanium dioxide (TiO(x)()) and carbon and the conclusions are verified using voltammetry at rotating disk electrodes. Gold centers with diameters in the range 1.4-6.3 nm were investigated and it is demonstrated that, with both supports, the catalytic activity for oxygen reduction decays rapidly for particle sizes below 3.0 nm. This may be observed as a decrease in current at constant potential or an increase in the overpotential for oxygen reduction.

We report the application of a new method for the high-throughput synthesis and screening of thin film materials and its application to the discovery of electrocatalysts. Results are presented for the PtPdAu ternary alloy system with respect to activity for oxygen reduction. The results reveal an enhancement in activity for a range of PtPd alloy compositions over either of the pure elements. An optimum composition range of ternary alloys with significant activity was also identified. A correlation was also investigated between the surface reduction potential and the activity for oxygen reduction in both binary and ternary alloys. The results demonstrate the potential of the methodology for the discovery and optimization of electrocatalysts for a wide range of applications.

A method that combines co-evaporation of pure elements from multiple finite-size sources on temperature-controlled substrates with independently controlled source shutters has been used for the synthesis of solid-state material combinatorial libraries. The source shutters are positioned to achieve a controlled gradient of the deposited elements across the substrate and are fixed during the course of deposition. Choice of the shutter position and the rate of deposition for each source allow the direct synthesis of continuous and controlled materials of varying composition. There are significant advantages of the method over alternatives which rely on sequential deposition and subsequent heat treatment to produce thin film materials. The parameters governing the creation of gradients have been identified and defined. Simulations and experimental data have been compared in the case of a single source. Results are presented for the synthesis of a ternary alloy library to demonstrate the methodology.

The reason for revision of primary total hip arthroplasty is quoted as aseptic loosening in 60.6% of cases between 1979 and 2003 in the Swedish National Hip Arthroplasty Registry. Much research effort has been directed toward enhancing the bone-cement interface of total joint arthroplasties, in an attempt to reduce this complication. Haemostatic agents have been popularized as effective means of retarding the development of potentially harmful debris interposition adjacent to, and blood lamination patterns within, the methylmethacrylate. Such agents include hydrogen peroxide (H(2)O(2)), local freezing saline, saline at room temperature and adrenaline solution. One main concern with the use of hydrogen peroxide is whether it affects the material properties of bone cement such that in the long term it contributes to aseptic loosening. This would have enormous clinical consequences. Preliminary studies indicate that porosity increases and that the tensile strength and yield stresses are reduced by up to a factor of 10 by contaminating samples with increasing concentrations of hydrogen peroxide. We postulate that the current use of hydrogen peroxide as an irrigation solution in arthroplasty contributes to the development of aseptic loosening.

In three experiments, location memory for faces was examined using a computer version of the matching game Concentration. Findings suggested that physical attractiveness led to more efficient matching for female faces but not for male faces. Study 3 revealed this interaction despite allowing participants to initially see, attend to, and match the attractive male faces in the first few turns. Analysis of matching errors suggested that, compared to other targets, attractive women were less confusable with one another. Results are discussed in terms of the different functions that attractiveness serves for men and women.

Aim: To analyze the evolution of total and food specific IgE (Rast Fx5) titers in the course of food allergy in children., Patients & Methods: 925 children, mean age 8.9 + 9.1 years (15 days-18 years), 455 girls and 470 boys, investigated for food allergy in year 1997, underwent serum samples assay for total IgE and of Rast Fx5, Cap System, Pharmacia & Upjohn Diagnostics AB, Uppsala, Sweden, a mix test detecting specific IgE to 6 major food allergens in children, cow's milk proteins (CMP), egg white, peanut, soy, wheat and fish and analyzed as a function of reference values by age., Results: Total IgE titers increased significantly with age, r0.22, p0.0001. The percentage of children with a total IgE level above normal range first increased with age, from 10.3 % at 0-6 months, reaching 38.2 % at 1-2 years and peaking at 56.9% at 4-6 years, then leveled off, 48.1% at 8-12 years (ns vs 4-6 years) and 41.3% above 12 years (ns). Detectable Rast Fx5 increased in a parallel manner until age 4-6 years and then exhibited a progressive decrease from age 6-8 years, differing significantly from total IgE: 31.9% vs 52.9%, p0.01 (6-8 years), 32.2% vs 48.1%, p0.03 (8-12 years), 21.8% vs 41.3%, p0.05 (> 12 years)., Conclusion: In these outpatient children investigated for food allergy, the increase with age of the percentage of high total IgE contrasted with the progressive decrease of Rast Fx5 from age 4-6 yr. This biological finding correlates timely with the clinical spontaneous decrease of food allergy in the developing child.

Twenty-nine couples in which one partner was depressed, 21 couples in which one partner had an anxiety disorder, and 26 nondistressed control couples were compared on measures of (1) quality of life, stress, and social support; (2) family functioning; (3) marital functioning; and (4) relationship attributions. The depressed group had significant difficulties in all four domains. In contrast, the control group showed minimal difficulties. The profile of the anxious group occupied an intermediate position between those of the other two groups, with some difficulties in all four domains, although these were less severe and pervasive than those of the depressed group.

Objectives: This study examined the prevalence of depressive symptoms, including suicidal ideation/behaviour, among bullied and non-bullied young people., Methods: Participants were 209 students, 97 male and 112 female, attending eight urban post-primary schools and aged between 12 and 15 years. Participants were interviewed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children - Present and Lifetime Version, the Hopelessness Scale for Children, the Scale for Suicide Ideation, and the Suicide Intent Scale., Results: Data were analysed using a series of non-parametric comparison tests. Being a victim of bullying was found to be significantly associated with depression (χ2 = 10.986; df = 1; p = 0.001) and suicidal ideation (χ2 = 5.811; df = 1; p = 0.022). Results also indicated that victims were more likely to have reported a suicide attempt (χ2 = 5.995; df = 1; p = 0.022). Finally, those bullied were significantly more likely to have been referred to psychiatric services (χ2 = 6.661; df = 1;p = 0.011)., Conclusions: These findings suggest that the issue of bullying needs to be re-addressed within Irish schools, with particular emphasis placed on further investigation into the psychological consequences thereof.

Practitioners of agent-based modeling are often tasked to model or design self-organizing systems while the theoretical foundation of self-organization in science remains to be set. This paper explores self-organization in the context of an agent-based model of ant colony food foraging. We gather specific measures of order-creation and constraint construction particular to leading theories of nonequilibrium thermodynamics that purport to govern self-organizing dynamics. These measures are used to explore three claims: (a) Constraints are constructed from entropy-producing processes in the bootstrapping phase of self-organizing systems; (b) positive feedback loops are critical in the structure formation phase; and (c) constraints tend to decay. The continued presence of far-from-equilibrium boundary conditions are required to reinforce constraints in the maintenance phase.

Purpose: The primary purpose of this study was to compare the neuropsychological performance of long-term survivors of breast cancer and lymphoma treated with standard dose chemotherapy who carried the epsilon 4 allele of the Apolipoprotein E (APOE) gene to those who carry other APOE alleles., Patients and Methods: Long-term survivors (mean=8.8+/-4.3 years post-treatment) of breast cancer (N=51, age=55.9+/-8.8) or lymphoma (N=29, age=55.8+/-11.6) who had been treated with standard-dose chemotherapy completed a standardized battery of neuropsychological and psychological tests. Survivors were also classified into two groups based on the presence (N=17) or absence (N=63) of at least one epsilon 4 allele of APOE., Results: Analysis of covariance, controlling for age, gender, education, diagnosis, and WRAT-3 reading subtest (a proxy measure of baseline IQ), indicated that survivors with at least one epsilon 4 allele scored significantly lower in the visual memory (p<0.03) and the spatial ability (p<0.05) domains and tended to score lower in the psychomotor functioning (p<0.08) domain as compared to survivors who did not carry an epsilon 4 allele. No group differences were found on depression, anxiety, or fatigue., Conclusions: The results of this study provide preliminary support for the hypothesis that the epsilon 4 allele of APOE may be a potential genetic marker for increased vulnerability to chemotherapy-induced cognitive decline., (Copyright 2003 John Wiley & Sons, Ltd.)

Palladium films with regular nanoarchitectures were electrochemically deposited from the hexagonal (H1) lyotropic liquid crystalline phase of the nonionic surfactant octaethyleneglycol monohexadecyl ether (C16EO8) onto micromachined silicon hotplate structures. The H1-e Pd films were shown to have high surface areas (approximately 28 m2 g(-1)) and to act as effective and stable catalysts for the detection of methane in air on heating to 500 degrees C. The response of the H1-e Pd-coated planar pellistors was found to be linearly proportional to the concentration of methane between 0 and 2.5% in air with a detection limit below 0.125%. Our results show that the electrochemical deposition of nanostructured metal films offers a promising approach to the fabrication of micromachined calorimetric gas sensors for combustible gases.

Thymocyte maturation is controlled by successive developmental checkpoints connected to the acquisition of a functional T cell receptor (TCR). During thymocyte selection, engagement of the TCR regulates the fine balance between death and survival signals. At the final stages of single-positive (SP) thymocyte maturation, the coupling of the TCR changes from death- to proliferation-inducing signals, a competence required for optimal effector functions in the periphery. We show here that in RelB mutant thymuses, thymocyte differentiation of CD24(-) SP cells is partially impaired. Competitive bone marrow reconstitution experiments show that this defect is constitutive to the lymphoid compartment. This is accompanied by an increased proportion of apoptotic thymocytes and a drastically reduced proliferation upon activation with anti-CD3 antibody/PMA stimulation. Thus, the RelB protein contributes to the quality of cell signaling in thymocytes by providing anti-apoptotic signals. These results suggest that in addition to its major role on the activation of antigen-presenting cell function, the RelB protein is intrinsically required for terminal thymocyte differentiation and activation.

The objective of this study was to explore the effects of increasing working memory (WM) processing load on previously observed abnormalities in activation of WM circuitry shortly after mild traumatic brain injury (MTBI). Brain activation patterns in response to increasing WM processing load (auditory n-back: 0-, 1-, 2-, and 3-back conditions) were assessed with fMRI in 18 MTBI patients within 1 month of their injury and in 12 healthy controls. Performance accuracy on these tasks was also measured. Brain activation patterns differed between MTBI patients and controls in response to increasing WM processing loads. Controls maintained their ability to increase activation in regions of WM circuitry with each increase in WM processing load. MTBI patients showed disproportionately increased activation during the moderate processing load condition, but very little increase in activation associated with the highest processing load condition. Task performance did not differ significantly between groups on any task condition. MTBI patients showed a different pattern of allocation of processing resources associated with a high processing load condition compared to healthy controls, despite similar task performance. This suggests that injury-related changes in ability to activate or modulate WM processing resources might underlie some of the memory complaints after MTBI., (Copyright 2001 Academic Press.)

Poly(ADP-ribose) polymerase-1 (PARP-1) catalyzes the rapid and extensive poly(ADP-ribosyl)ation of nuclear proteins in response to DNA strand breaks, and its expression, although ubiquitous, is modulated from tissue to tissue and during cellular differentiation. PARP-1 gene promoters from human, rat, and mouse have been cloned, and they share a structure common to housekeeping genes, as they lack a functional TATA box and contain multiple GC boxes, which bind the transcriptional activator Sp1. We have previously shown that, although Sp1 is important for rat PARP1 (rPARP) promoter activity, its finely tuned modulation is likely dependent on other transcription factors that bind the rPARP proximal promoter in vitro. In this study, we identified one such factor as NF1-L, a rat liver isoform of the nuclear factor 1 family of transcription factors. The NF1-L site on the rPARP promoter overlaps one of the Sp1 binding sites previously identified, and we demonstrated that binding of both factors to this composite element is mutually exclusive. Furthermore, we provide evidence that NF1-L has no effect by itself on rPARP promoter activity, but rather down-regulates the Sp1 activity by interfering with its ability to bind the rPARP promoter in order to modulate transcription of the rPARP gene.

The effect of dietary fibre on the gastric emptying rate of solids is controversial. Similarly, the mechanisms by which it modulates food intake are partially unknown. Gastric emptying and proximal v. distal stomach filling were evaluated in triplicate on four conscious pigs using scintigraphic imaging. Each animal received in an isoenergetic manner a concentrate low-fibre diet enriched in starch (S) and two high-fibre diets based on sugar beet pulp (BP) or wheat bran (WB). All meals had the same viscosity before ingestion (100.0-100.5 Pa.s). Viscosity of the gastric contents was measured in four additional animals fitted with a gastric cannula. The gastric emptying rate of BP diet was significantly slower than S and WB diets (t1/2 78.4 (sem 5.68), 62.8 (sem 10.01) and 111.6 (sem 10.82) min for S, WB and BP diets respectively, P<0.05). For BP diet only, rate of distal stomach filling was steady during the first 120 min after the meal whereas that of S and WB diets decreased in an exponential manner. Numerous backflow episodes from the distal into the proximal stomach were observed for BP diet that generated the larger intragastric viscosity (0.26 (sem 0.03), 0.3 (sem 0.02) and 0.52 (sem 0.002) Pa.s for S, WB and BP respectively). In conclusion, viscosity of the meal or the percentage total fibre, unlike viscosity of the gastric contents, are poor predictors for emptying. The reduced emptying rate observed with BP is associated with major changes in intragastric distribution of the meal absent with WB and S diets.

Objective: To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury (MTBI)., Background: Many individuals complain of memory difficulty shortly after MTBI. Memory performance in these individuals can be normal despite these complaints., Methods: Brain activation patterns in response to a working memory task (auditory n-back) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects., Results: Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads. Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load, with little additional increase in activation associated with the high load task. MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition, particularly in the right parietal and right dorsolateral frontal regions. Task performance did not differ significantly between groups., Conclusion: MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads, despite similar task performance. This suggests that injury-related changes in ability to activate or to modulate working memory processing resources may underlie some of the memory complaints after MTBI.

Results of recent functional magnetic resonance imaging (fMRI) studies of memory are not entirely consistent with lesion studies. Furthermore, although imaging probes have identified neural systems associated with processing novel visual episodic information, auditory verbal memory using a novel/familiar paradigm has not yet been examined. To address this gap, fMRI was used to compare the haemodynamic response when listening to recently learned and novel words. Sixteen healthy adults (6 male, 10 female) learned a 10-item word list to 100% criterion, approximately 1 h before functional scanning. During echo-planar imaging, subjects passively listened to a string of words presented at 6-s intervals. Previously learned words were interspersed pseudo-randomly between novel words. Mean scans corresponding to each word type were analysed with a random-effects model using statistical parametric mapping (SPM96). Familiar (learned) words activated the right prefrontal cortex, posterior left parahippocampal gyrus, left medial parietal cortex and right superior temporal gyrus. Novel words activated the anterior left hippocampal region. The results for the familiar words were similar to those found in other functional imaging studies of recognition and retrieval and implicate the right dorsolateral prefrontal and left posterior medial temporal lobe (MTL) regions. The results for novel words require replication, but are consistent with the substantial lesion and PET literature implicating the anterior MTL as a critical site for processing novel episodic information, presumably to permit encoding. Together, these results provide evidence for an anterior-posterior functional differentiation within the MTL in processing novel and familiar verbal information. The differentiation of MTL functions that was obtained is consistent with a large body of PET activation studies but is unique among fMRI studies, which to date have differed from results with PET. Further, the finding of left MTL lateralization is consistent with lesion-based material-specific models of memory.

Ligation of Fas with its natural ligand or with anti-Fas antibodies induces an apoptotic program in Fas sensitive cells. We report here the identification of the tyrosine kinase p59Fyn as a substrate for CPP32-like proteinases and more particularly caspase 3 during Fas-mediated apoptosis in Jurkat T cells. Inhibition of CPP32-like proteinases by Ac-Asp-Glu-Val-Asp-aldehyde but not by Ac-Tyr-Val-Ala-Asp-aldehyde prevents CPP32, PARP and p59Fyn cleavage indicating that CPP32 or CPP32-like proteinases are responsible for the cleavage of p59Fyn. Cleavage occurs in the N-terminal domain of p59Fyn between Asp19 and Gly20 and is accompanied by relocation of an active p57Fyn kinase to cytoplasm of Fas-stimulated Jurkat cells as judged by both biochemical and confocal microscopy experiments. Thus, p59Fyn relocation and activity may play an important role during Fas-mediated cell death in human T lymphocytes.

We present a perturbative analysis of Floquet eigenstates in the context of two delayed laser processes (STIRAP) in three level systems. We show the efficiency of a systematic perturbative development which can be applied as long as no non-linear resonances occur.

Highly comminuted supracondylar humeral fractures were stabilised in six large-breed dogs with a modified type I external fixator using a craniomedial acrylic connecting column and an intramedullary pin which was incorporated into the connecting frame. This construct provided sufficient stability to allow satisfactory bone healing in five of the six dogs, while premature removal of the intramedullary pin and external fixator resulted in subsequent refracture of the humerus in the remaining dog. Limb function at the time of final assessment was considered excellent in two dogs, good in three dogs and poor in one dog. The craniomedial acrylic connecting column simplified application of this modified type I(a) configuration to the humerus by reducing the number of clamps required; the acrylic column also facilitated contouring of the craniomedial connecting column to the brachium and was readily extended proximally to engage the intramedullary pin. In addition, the acrylic connecting column allowed placement of intramedullary pins of varying diameter.

Cells of the M1D+ murine myeloid leukemic cell line differentiate into macrophages in response to either leukemia inhibitory factor (LIF) or interleukin 6. Previously, it was shown that LIF treatment of M1D+ cells leads to an increased expression of colony-stimulating factor (CSF) receptor mRNA encoded by c-fms. CSF-1, a macrophage growth factor, induces the survival, growth, and differentiation of mononuclear phagocytes but has not been implicated in the regulation of early myeloid cell differentiation. Here we show that low-dose LIF treatment of M1D+ cells results in CSF-1 secretion and CSF-1 receptor up-regulation. CSF-1, when applied alone, induces some M1D+ adherence and the up-regulation of lysozyme M, a macrophage-specific marker. Finally, we show that when applied together, LIF and CSF-1 act synergistically to induce macrophage morphology, phagocytosis, and the expression of the macrophage-specific markers CD11b/Mac-1 alpha chain, lysozyme M, FcgammaRII, and JE/MCP.1. These results indicate that instead of being part of exclusive pathways, as thought until this work, LIF and CSF-1 can function synergistically to further stimulate the early stages of myeloid differentiation.

An eight-and-a-half-year-old rottweiler bitch was examined on four separate occasions over a period of 32 months for lameness caused by a mass on a digit. On each occasion the mass and affected digit were amputated. Three different neoplasms were diagnosed: two squamous cell carcinomas, a melanocytoma and an intracutaneous cornifying epithelioma. There was no recurrence following surgical excision.

A previous study using single photon absorptiometry has reported low bone mineral density of the radius in infants of diabetic mothers. The aim of this study was to assess by dual x-ray absorptiometry the whole body bone mineral content (WbBMC) and the body composition of 40 infants of diabetic mothers at birth (mean gestational age +/- SD, 37.5 +/- 1.3 weeks; mean birth weight +/- SD, 3815 +/- 641 g). WbBMC was not correlated with gestational age, but was well correlated with birth weight (r = 0.73; P = 0.0001) and also with fat mass (r = 0.87; P = 0.0001) and lean mass (r = 0.42; P = 0.008). The z-scores +/- SD adjusted for weight for WbBMC and fat mass were significantly increased (1.3 +/- 0.9 and 2.6 +/- 1.3, respectively (P < 0.0001), but were not significantly influenced either by in utero growth or by the type of the diabetes mellitus of the mother. Bone mineralization and fat mass studied by whole body dual x-ray absorptiometry are increased at birth in these infants compared with reference curves.

Jurkat T cells express a functional endopeptidase 24.11 that is involved in the regulation of T cell activation. We have analyzed the effect of ectopic CD10 expression in mutant Jurkat cell clones that fail to express CD10 and, unlike wild-type cells, are resistant to the growth-inhibitory effects of the protein kinase C activator, PMA. No differences in the expression of the mRNA encoding the alpha, beta, gamma, delta, epsilon, and zeta isoforms of PKC were found in parental vs. PMA-resistant Jurkat cells, ruling out the possibility that the defect could be accounted for by an altered expression of one of these isoforms. Phorbol ester-induced growth arrest was not due to apoptosis since PMA failed to trigger DNA fragmentation in parental and mutant Jurkat T cells. CD10 mRNA expression and activity were abrogated in four independent PMA-resistant Jurkat T cell clones compared to parental cells, whereas the activities of several other peptidases were unaffected. Transfection of one mutant clone with a functional endopeptidase 24.11 restored in a significant manner PMA-induced growth arrest in all the clones selected and tested, whereas transfection of an inactive form of endopeptidase 24.11 had no effect, demonstrating that the enzymatic activity of CD10 is critical in the mediation of the PMA growth arrest. The data presented here demonstrate that a functional CD10 is required for PMA-induced growth arrest in Jurkat cells and provide further evidence for a role of endopeptidase 24.11 in the regulation of tumor cell proliferation.

Seven cases of tarsocrural subluxation/luxation resulting from ruptures of the medial collateral ligament were treated by double prosthetic replacement. The technique was a revision of an earlier described method without the use of metallic implants. Six (100%) of six cases not involving additional joint fractures had excellent clinical results with minimal compromise to range of joint motion. In three (50%) of six cases where braided polyester sutures were implanted as the prosthesis, fistulating tracts developed. Drainage resolved with removal of the suture in each of these three cases, and two of the three proceeded to excellent results after replacing the braided suture with monofilament suture.

Human immature thymocytes express significant levels of the CD10 (endopeptidase 24.11) cell surface antigen. We report here that IOB5, an anti-CD10 mAb, as well as the phorbol ester PMA down-regulate CD10 activity at the surface of human thymocytes. The kinetics of CD10 modulation were drastically different for both effectors, indicating different regulatory mechanisms. We also demonstrated that intact human thymocytes hydrolyze thymopentin and that CD10 significantly participates in this process. Finally, we found that thymopentin and to a lesser extent phosphoramidon, a specific endopeptidase 24.11 inhibitor, induced up-regulation of CD4 and CD8 molecules at the thymocyte cell surface. In view of these results, we suggest that down-regulation of endopeptidase 24.11 at the thymocyte cell surface might reduce its activity toward thymic factors possibly involved in the regulation of thymocyte functions.

This study was conducted to determine whether serine proteinases may induce [Ca(2+)]i mobilization in different hematopoietic cell lines and to analyze their mechanisms of action. We show that in addition to thrombin and thrombin receptor agonist peptide (TRP, SFLLRN), trypsin induced [Ca(2+)]i mobilization in a highly thrombin-sensitive Jurkat T cell clone. Thrombin, TRP, and trypsin were found to induce [Ca(2+)]i release in three different Jurkat T cell clones differing in the level of T cell receptor expression. Similar results were obtained with a prothymocytic leukemic cell line, HPB.ALL, although these cells were much more responsive to trypsin than to thrombin and TRP. Other cell types such as THP1, a myelomonocytic cell line, or CEM, a CD4(+) positive leukemic cell line, were unresponsive to thrombin, TRP, and trypsin. The effect of trypsin was mimicked by SLIGRL, a peptide corresponding to the cleaved amino-terminal sequence of the recently characterized murine trypsin-activated receptor (PAR2). At suboptimal concentrations, the effects of SFLLRN and SLIGRL were additive, whereas saturating doses of peptides did not further increase [Ca(2+)]i mobilization in Jurkat T cells, indicating that both peptides were able to mobilize the same pool of calcium. Northern blot analysis of mRNAs from different leukemic cell lines indicated a remarkable correlation between PAR2 expression in different cell lines and SLIGRL or trypsin responses in the same cells. The expression of the "trypsin receptor" was also confirmed by polymerase chain reaction analysis. Moreover, a 24 h treatment of Jurkat cells by an anti-CD3 monoclonal antibody, a condition known to down-regulate thrombin receptor expression, induced loss of thrombin and TRP responses but only partially affected trypsin stimulation of [Ca(2+)]i release. Finally, after a first stimulation with either thrombin or trypsin, Jurkat cells were still able to respond to trypsin or thrombin, respectively, demonstrating that thrombin and trypsin essentially activated their own receptors. Our data provided evidence that 1) the human T leukemic cell line Jurkat and other T cell lines express at least two different functional protease-activated receptors, the thrombin receptor and a highly sensitive trypsin receptor, likely the human counterpart of the murine PAR2, and 2) at variance with the commonly accepted model, trypsin exerts most of its effect in T leukemic cell lines by thrombin receptor-independent mechanisms.

A technique of lag-screw fixation for ununited anconeal process is described, and the results of surgery in eight dogs (on 10 elbows) treated by this technique are presented. Approximation of the process was confirmed postoperatively, and union was confirmed by radiographic followup in six of the 10 forelimbs from two-to-six months after surgery. Four other cases were lost to radiographic follow-up. This report of a limited number of cases suggests encouraging results obtained by lag-screw fixation.

Two clinical cases of broncho-oesophageal fistula in the dog are presented. While both cases illustrate the value of oesophagoscopy as a diagnostic tool, one case depicts the complications which may be associated with positive contrast oesophagography. These two cases support previous observations that broncho-oesophageal fistulae are frequently of foreign body aetiology and usually extend from the caudal oesophagus, via the pleural space, to the caudal or middle right lung lobes.

The results of 12 dogs with antebrachial deformity treated by ulnar ostectomy, radial osteotomy and external skeletal fixation are presented. Postoperative complications were seen in only one dog; a delayed union requiring placement of autogenous cancellous bone graft at a second surgery to achieve healing. Postoperatively, owners reported limb function was good in almost all cases, although they were less pleased with the cosmetic appearance.

Although it is now well established that cells of the immune system express most of the exopeptidases described so far, little information is available concerning the identification and the characterization of the peptidases associated with the surface of human thymocytes. In the present study we have focused on CD10 expression on thymocytes using both FACS and enzymatic analysis. Unfractionated intact human thymocytes were shown to express significant levels of CD10-specific enzymatic activity, as assessed by the hydrolysis of the neutral endopeptidase (NEP) substrate Suc-Ala-Ala-Phe-pNA and of D-Ala2-Leu-enkephalin, a typical NEP substrate. CD10 activity was abolished by specific NEP inhibitors, including thiorphan, retrothiorphan and phosphoramidon. Moreover, high performance liquid chromatography (HPLC) analysis showed that intact thymocytes and purified NEP hydrolysed thymopentin, a thymic factor known to induce the maturation of prothymocytes into thymocytes. Finally, CD 10/NEP was preferentially associated with CD3- CD3low and immature CD4- CD8- thymocytes. The data demonstrate for the first time that human thymocytes express functional NEP and suggest a role for this enzyme in the maturation of human thymocytes.

The eosinophilia-myalgia syndrome (EMS) associated with the ingestion of L-tryptophan (LT) containing products has recently been recognized in the United States. We report the histologic features of the cutaneous scleroderma-like changes in four patients. All of the patients met the Center for Disease Control criteria for EMS and had a history of LT ingestion. Skin biopsies showed increased dermal mucin and dermal sclerosis, with trapping of adnexal structures. There are clinical and histologic similarities between EMS, scleroderma, the toxic oil syndrome, and fasciitis with eosinophils.

The mouse H-2 multigene family includes the genes coding for the major transplantation antigens and for genes located in the Qa-TIa region. We have studied a collection of class I cDNA clones made from liver mRNA of DBA/2 mice (H-2d haplotype) and found that at least six distinct class I genes are transcribed, including three genes of the Qa-TIa region. Two of these six genes each yield two distinct mRNAs, resulting from alternate splicing. Altogether, liver cells may express at least eight distinct class I polypeptides, of which three might be secreted, while one may be a new presumptive nonpolymorphic surface antigen.

We report on two patients with mosaic tetrasomy of 8p[46,XY/47,XY,+i(8p)], a previously unreported cytogenetic anomaly. The first patient had a low percentage of tetrasomic (secondary trisomic) cells in lymphocytes and fibroblasts, an only mildly abnormal phenotype, and a rather benign clinical course. The second patient had a considerably larger percentage of tetrasomic cells in lymphocytes and fibroblasts, and had more severe congenital anomalies that led to his death at 8 months. A characteristic phenotype +i(8p) is suggested but not yet established. The manifestations of these two patients resemble those of mosaic trisomy 8 and mosaic trisomy 8p, with rib and vertebral abnormalities, absent corpus callosum, and enlarged cerebral ventricles.

Patients with coeliac disease have a highly significant reduction in the release of secretin and gastric inhibitory polypeptide from the upper small intestine, but a greatly increased release of enteroglucagon, and also of neurotensin, from the lower part of the small intestine. The release of gastrin and pancreatic polypeptide, from the antrum and pancreas respectively, is, however, normal. Thus the pattern of hormone release reflects the location of the mucosal lesion. The gut-hormone profile may also help to characterise other gastrointestinal diseases.

The cephalosporinase gene, cpa, which codes for an inducible class I chromosomal beta-lactamase in Enterobacter cloacae was cloned on a fragment of 6.05 kilobase pairs inserted into plasmid pACYC184 and transferred into Escherichia coli HB101 recipient cells. The constructed hybrid plasmid, designated pGGQ101, carried a genomic fragment which retained its parental inducibility characteristics, although its expression level in transformed E. coli cells fell to 40-65% of its initial level in E. cloacae. The localization of the cpa gene on pGGQ101 plasmid was determined by Bal31 exonuclease deletion mapping and further confirmed by subcloning HindIII-AvaI restriction fragment on pMB9 plasmid vector. Labeling with [35S]methionine of pGGQ101 specified proteins in a minicell system showed that six or seven proteins are encoded by the insert. Two proteins with apparent molecular mass of 42 000 and 39 500 daltons, respectively, most probably represent the premature and mature cephalosporinase forms.

Fasting and postprandial levels of gastrin, insulin, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, enteroglucagon and neurotensin were measured in 42 patients with irritable bowel syndrome (IBS). No overall major abnormalities of secretion of any of these peptides were found, although minor differences from normal of pancreatic polypeptide and neurotensin were observed. It is doubtful whether abnormalities of gut hormone secretion play an important role in the pathophysiology of IBS.

Pancreatic and gut hormones have been measured in 39 patients with chronic pancreatitis, 16 of whom had severe pancreatic insufficiency. Patients with pancreatic insufficiency had significantly diminished fasting levels and postprandial rises of pancreatic polypeptide which were less than 20% of normal. Patients with chronic pancreatitis, with or without exocrine insufficiency, had two- to threefold higher plasma levels of motilin and enteroglucagon than controls. Plasma levels of insulin, pancreatic glucagon, gastric inhibitory polypeptide and gastrin were similar to normal in these patients. The pattern of response of these hormones to a test breakfast differs markedly from those seen in other gut disease states and may reflect pathophysiological mechanisms.

The ampR gene and its regulation of AmpC beta-lactamase synthesis were investigated for Enterobacter cloacae 1194E, a wild-type strain producing a group A (pI 8.7) enzyme. Expression of the cloned E. cloacae 1194E ampR-ampC region was examined initially in Escherichia coli HB101. However, transformants showed only constitutive beta-lactamase expression. For study of enzyme expression in a more closely related host, the cloned E. cloacae 1194E ampR-ampC region was transformed into E. cloacae 55, a wild-type strain producing a group B (pI 7.8) enzyme. Results indicated a functional E. cloacae 1194E ampR gene that could not be transcomplemented by E. cloacae 55. A comparative analysis of ampR nucleotide and amino acid-sequence data from E. cloacae 1194E and E. cloacae MHN1 revealed related but divergent genes. Thermal induction studies of AmpC beta-lactamase also indicated a difference between E. cloacae 1194E and E. cloacae 55 in ampR-ampC interaction. Thus, it appears that, in at least some strains of Enterobacter, significant intraspecies divergence of ampR has occurred. This heterogeneity in ampR would not have been detected with beta-lactamase expression studies conducted exclusively in E. coli.