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Herein we show that hybridisation of buckybowl corannulene and thiophene-S,S-dioxide motifs is a general approach for the preparation of high electron affinity molecular materials. The devised synthesis is modular and relies on thienannulation of corannnulene-based phenylacetylene scaffolds. The final compounds are highly soluble in common organic solvents. These compounds also exhibit interesting optical properties such as absorption and emission in the blue/green regions of the electromagnetic spectrum. Importantly, a bis-S,S-dioxide derivative exhibits three reversible reductions similar in their strength to the prevalent fullerene-based electron acceptor phenyl-C61 -butyric acid methyl ester (PC61 BM). Ministry of Education (MOE) Financial support from the Ministry of Education Singapore under the AcRF Tier 1 (MOET1 RG11/21) and AcRF Tier 2 (MOE-T2EP10221-0002) is gratefully acknowledged. The support of the grant “REGRENPOS”PN-III-P2-2.1-PED-2019-2601, founded by the Romanian Ministry of Education and Research is also acknowledged.

Angioimmunoblastic T‐cell lymphoma (AITL) is a neoplastic proliferation of T follicular helper cells with clinical and histological presentations suggesting a role of antigenic drive in its development. Genetically, it is characterized by a stepwise acquisition of somatic mutations, with early mutations involving epigenetic regulators (TET2, DNMT3A) and occurring in haematopoietic stem cells, with subsequent changes involving signaling molecules (RHOA, VAV1, PLCG1, CD28) critical for T‐cell biology. To search for evidence of potential oncogenic cooperation between genetic changes and intrinsic T cell receptor (TCR) signaling, we investigated somatic mutations and T‐cell receptor β (TRB) rearrangement in 119 AITL, 11 peripheral T‐cell lymphomas with T follicular helper phenotype (PTCL‐TFH), and 25 PTCL‐NOS using Fluidigm polymerase chain reaction (PCR) and Illumina MiSeq sequencing. We confirmed frequent TET2, DNMT3A, and RHOA mutations in AITL (72%, 34%, 61%) and PTCL‐TFH (73%, 36%, 45%) and showed multiple TET2 mutations (2 or 3) in 57% of the involved AITL and PTCL‐TFH. Clonal TRB rearrangement was seen in 76 cases with multiple functional rearrangements (2–4) in 18 cases (24%). In selected cases, we confirmed bi‐clonal T‐cell populations and further demonstrated that these independent T‐cell populations harboured identical TET2 mutations by using BaseScope in situ hybridization, suggesting their derivation from a common TET2 mutant progenitor cell population. Furthermore, both T‐cell populations expressed CD4. Finally, in comparison with tonsillar TFH cells, both AITL and PTCL‐TFH showed a significant overrepresentation of several TRB variable family members, particularly TRBV19*01. Our findings suggest the presence of parallel neoplastic evolutions from a common TET2 mutant haematopoietic progenitor pool in AITL and PTCL‐TFH, albeit to be confirmed in a large series of cases. The biased TRBV usage in these lymphomas suggests that antigenic stimulation may play an important role in predilection of T cells to clonal expansion and malignant transformation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Satellite estimation of accumulated precipitation is an important facet of the study of the tropical water cycle. An advanced data merging approach using infrared geostationary imagery and microwave constellation based instantaneous rain rate estimates has been implemented in the framework of the Megha-Tropiques and Global Precipitation Measurements missions. The Tropical Amount of Rainfall with Estimation of ERors (TAPEER) algorithm has been tailored to account for the loss of the MADRAS conical scanning radiometer by using the SAPHIR sounder rainfall detection capability, thanks to a novel two-constellation implementation of the algorithm. A new bias correction module based on the TRMM PR observations is also presented. The performances of this new version of the product are reviewed with emphasis on West Africa. In particular, using data-denial experiments, the contribution of SAPHIR data to the rainfall daily accumulation is quantified for various configurations of the microwave constellation and various algorithmic parameter selections. The results show that the daily accumulation statistics are well improved when SAPHIR is taken into the constellation. The improvements can be quantified using bulk statistics but are more evident following a frequency analysis. The pattern of the impact is a complex convolution of rainfall occurrence and of the Megha-Tropiques mission original sampling. Over the 20 degrees N-20 degrees S belt, in zonal mean, the inclusion of SAPHIR data alters the daily accumulation substantially (more than 50% of the daily accumulation) more than 10% of the time and more than 20% when conditioned upon rainfall. Under both metrics, the improvement is majored in the 12 degrees-17 degrees latitude band where the Megha-Tropiques mission sampling is at its maximum.

AIMS: The aim of this study was to evaluate the drug–drug interaction between pimodivir, a novel, non‐nucleoside polymerase basic protein 2 (PB2) subunit inhibitor of the influenza A virus polymerase complex, and oseltamivir, to assess the feasibility of this combination therapy. Furthermore, single‐ and multiple‐dose pharmacokinetics and safety of pimodivir in healthy volunteers were assessed. METHODS: In Part 1 of this open‐label Phase 1 study, healthy volunteers (n = 18) were randomized to one of six cross‐over treatment sequences, each comprising administration of oseltamivir 75 mg or pimodivir 600 mg or combination thereof twice daily on Days 1–4, followed by a single morning dose on Day 5. Between each treatment session, there was a minimum 5‐day washout period. In Part 2, healthy volunteers (n = 16) randomly received pimodivir 600 mg or placebo (3:1) twice daily on Days 1–9, followed by a single morning dose on Day 10. Pharmacokinetics of pimodivir, oseltamivir and oseltamivir carboxylate, and safety were assessed. RESULTS: In Part 1, co‐administration of pimodivir with oseltamivir increased the C (max) of pimodivir by 31% (90% CI: 0.92–1.85) with no change in C (min) or AUC(12h). Pimodivir had no effect on oseltamivir or oseltamivir carboxylate pharmacokinetics. In Part 2, after single‐ and multiple‐dose administration of pimodivir, there was a 1.2‐ and 1.8‐fold increase in C (max) and AUC(12h), respectively, between Day 1 and Day 10. The most frequently reported treatment‐emergent adverse event was diarrhoea (n = 7 each in Part 1 and 2). CONCLUSION: Combination treatment with pimodivir and oseltamivir in healthy volunteers showed no clinically relevant drug–drug interactions. No safety concerns were identified with pimodivir 600 mg twice daily alone or in combination with oseltamivir 75 mg twice daily.

Aims This study investigates the link between personal income and smoking among adolescents, and aims to answer the following questions: (i) to what extent is personal income related to smoking, independent of family socio-economic status (SES) and (ii) does the association between personal income and smoking apply to different subpopulations? Design Cross-sectional study. Setting Six cities from European countries (Amersfoort, the Netherlands; Coimbra, Portugal; Hannover, Germany; Latina, Italy; Namur, Belgium; Tampere, Finland) in 2013. Participants A school-based sample of 10 794 adolescents aged 14–17 years. Measurements We modelled smoking experimentation, weekly smoking, daily smoking and (among daily smokers) smoking intensity as function of personal income, adjusting for age, sex, family SES, parental smoking and country. We tested interactions between personal income and covariates. Stratification analyses were performed for the variables for which interactions were significant. Findings Adolescents in the highest income quintile were more likely to be smoking experimenters [odds ratio (OR) = 1.87; P

In light of increasing losses from floods, many researchers and policymakers are looking for ways to encourage flood risk reduction among communities, business, and households. In this study, we investigate risk-reduction behavior at the household level in three European Union Member States with fundamentally different insurance and compensation schemes. We try to understand if and how insurance and public assistance influence private risk-reduction behavior. Data were collected using a telephone survey (n = 1,849) of household decisionmakers in flood-prone areas. We show that insurance overall is positively associated with private risk-reduction behavior. Warranties, premium discounts, and information provision with respect to risk reduction may be an explanation for this positive relationship in the case of structural measures. Public incentives for risk-reduction measures by means of financial and in-kind support, and particularly through the provision of information, are also associated with enhancing risk reduction. In this study, public compensation is not negatively associated with private risk-reduction behavior. This does not disprove such a relationship, but the negative effect may be mitigated by factors related to respondents' capacity to implement measures or social norms that were not included in the analysis. The data suggest that large-scale flood protection infrastructure creates a sense of security that is associated with a lower level of preparedness. Across the board there is ample room to improve both public and private policies to provide effective incentives for household-level risk reduction.

A new all-solid-state pH sensor combining an Ion-Selective Electrode (ISE) for pH measurements and an all-solid-state reference electrode using a lithium ion conducting ceramic is presented. The use of a liquid internal reference in commercialized pH and reference electrodes leads to important drawbacks that considerably limit their use for in-situ measurements. The manufacturing and properties of an all-solid-state reference electrode made of the ceramic Li0.3La0.57TiO3 (LLTO) and an all-solid-state pH microelectrode are described. Both electrodes are combined to prepare an all-solid-state pH sensor which can be used in different applications such as medicine, food industry or oil or water drilling industries.

Background: Nitrones such as 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) are known to trap and stabilize free radicals and to reduce inflammation. Recently, S-PBN was shown to reduce infiltration o ...

Several extracellular matrix substances, such as hyaluronan and fibronectin, may affect graft viability by their involvement in cell adhesion and in migration. These substances are produced locally in the tissue by fibroblasts. The aim of this study was to investigate the activation state of intragraft fibroblasts under various immunosuppressive treatments and to correlate these with morphological parameters. Syngeneic (n = 5) and allogeneic rat (n = 5-6/group) heterotopic heart transplantations were performed. Allogeneically transplanted animals were immunosuppressed with cyclosporine, mycophenolate mofetil or prednisolone. After 10 days, the transplanted hearts were removed for subsequent isolation of intragraft fibroblasts and for evaluation of graft morphology. The hyaluronan synthesis of graft fibroblasts correlated with the cellular infiltration (p < 0.05) and the interstitial oedema (p < 0.05) of the cardiac grafts. In general, proliferation rate and hyaluronan production were of the same magnitude in fibroblasts from allogeneic hearts under immunosuppression with cyclosporine, mycophenolate mofetil or prednisolone as in fibroblasts from syngeneic grafts. A pool of fibroblasts isolated from cardiac grafts of non-immunosuppressed, allogeneically transplanted rats (n = 4) showed considerably higher levels. We concluded that fibroblast activity correlates to the viability of the tissue rather than to the specific drug used for immunosuppression.

Most of the currently known light-harvesting complexes 2 (LH2) rings are formed by 8 or 9 subunits. As of now, questions like "what factors govern the LH2 ring size?" and "are there other ring sizes possible?" remain largely unanswered. Here, we investigate by means of molecular dynamics (MD) simulations and stochastic modeling the possibility of predicting the size of an LH2 ring from the sole knowledge of the high resolution crystal structure of a single subunit. Starting with single subunits of two LH2 rings with known size, that is, an 8-ring from Rs. moliscianum (MOLI) and a 9-ring from Rps. acidophila (ACI), and one with unknown size (referred to as X), we build atomic models of subunit dimers corresponding to assumed 8-, 9-, and 10-ring geometries. After inserting each of the dimers into a lipid-water environment, we determine the preferred angle between the corresponding subunits by three methods: (1) energy minimization, (2) free MD simulations, and (3) potential of mean force calculations. We find that the results from all three methods are consistent with each other, and when taken together, it allows one to predict with reasonable level of confidence the sizes of the corresponding ring structures. One finds that X and ACI very likely form a 9-ring, while MOLI is more likely to form an 8-ring than a 9-ring. Finally, we discuss both the merits and limitations of all three prediction methods.

Aim: The impact of mandatory immunosuppression on liver regeneration after segmental liver transplantation is of clinical importance. FK778, a novel immunosuppressant, inhibits pyrimidine biosynthesis and prevents rejection after organ transplantation in a dose-dependent manner. We investigated the effect of FK778 at a highly effective dose on liver regeneration in a small animal model. Methods: Inbred Lewis rats were subjected to 70% partial hepatectomy (PH) and treated with saline (n = 28), uridine (n = 16), FK778 alone (n = 28) or in combination with uridine (n = 16). FK778 was given intravenously daily at a dose of 25 mg/kg bodyweight (bw) and uridine was given daily intraperitoneally at a dose of 250 mg/kg bw. Liver bodyweight ratio (LBR), hepatocyte proliferation index (PI), blood chemistry and morphological analysis were incorporated. PI was determined by Ki-67 immunostaining. De Ritis ratio was calculated to assess the extent of liver damage. Results: In FK778-treated animals PI was decreased at 24 h and 72 h and LBR was lower at 48 h and 72 h (P

Antibodies play a crucial role in the rejection of an organ that has been transplanted between different animal species, i.e. xenotransplantation. In previous work, we have induced a state of humoral tolerance where mouse-to-rat heart grafts continued to beat under ciclosporine A monotherapy. Initially, a combined treatment with ciclosporine A and 15-deoxyspergualin was given. This state of tolerance could not be reproduced when the vascularised heart graft was replaced with a free tissue graft or xenogeneic blood transfusions. To gain further insight into the humoral response against mouse antigens, we studied the antibody production in naive rats and rats challenged with heart transplants, heart cells, mononuclear cells (MNC) and erythrocytes from mice. Rats not challenged with any mouse cells or organs had a moderate amount of antibodies targeted against mouse MNC as well as rosette-forming cells in the spleen targeted against mouse erythrocytes. A challenge with either mouse MNC or erythrocytes lead to immunisation with antibodies of both IgM and IgG subtype directed against both MNC and erythrocytes. Antibody titres against mouse erythrocytes in animals challenged with MNC were not detectable until day 7, whereas antibody titres against mouse MNC in animals challenged with erythrocytes were detected on day 1. Immunisation with mouse erythrocytes raised the titre of rosette-forming cells in the spleen compared with naive rats (P < 0.05). Our data indicate that different xenogeneic antigens in the mouse-to-rat system are shared between heart cells, MNC and erythrocytes; however, the immunisation patterns differ regarding the time when antibodies are first detected.

Inherent properties of dendritic cell (DC) subsets are important in the regulation of naïve T-cell differentiation (e.g. Th1 versus Th2 cells), whereas effector memory T cells are believed to produce a fixed cytokine repertoire independent of the type of antigen presenting cell. Here we show that two distinct human DC subsets, plasmacytoid DC (PDC) and myeloid CD11c+ DC, induced autologous mumps virus-specific memory CD4(+) T cells to produce markedly different cytokine patterns upon antigen stimulation. PDC stimulated the T cells to produce gamma-interferon (IFN-gamma) and interleukin-(IL)-10, whereas CD11c+ DC induced lower levels of IFN-gamma, virtually no IL-10, but significant levels of IL-5. Analysis of intracellular cytokine production showed simultaneous production of IL-10 and IFN-gamma in mumps-specific T cells activated by PDC, a cytokine pattern similar to that described for Th1-like regulatory cells. Introduction of CpG oligodeoxynucleotides in PDC/T-cell co-cultures had synergistic effect on virus-dependent IFN-gamma production, whereas the other cytokines remained unchanged. Together, our results show that the type of DC involved in reactivation of previously primed T cells may have significant impact on the resulting cytokine response and suggest that targeting of viral antigens and adjuvant to specific DC subsets should be considered in the design of therapeutic antiviral vaccines.

The hygiene hypothesis implies that the increasing prevalence of allergy in 'westernized' countries is explained by reduced bacterial exposure in early life, but the underlying mechanism remains elusive. We therefore wanted to study the effect of bacterial lipopolysaccharide (LPS) on the generation of regulatory T (T R ) cells in neonates, and to analyze differences between neonates with allergy risk because of a family history of atopy (FH + ) and controls without such hereditary risk (FH - ). Cord blood mononuclear cells from the FH + and FH - groups were stimulated with β-lactoglobulin in the presence of LPS. T-cell phenotypes suggestive of T R cells [CD25 + , CD25 high and integrin α E (CD103 + )], and the intracellular proliferation antigen Ki-67 were quantified by flow cytometry. Release of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) from its inactive complex was determined by enzyme-linked immunosorbent assay. The analyses revealed the generation of T-cell phenotypes suggestive of T R cells including a CD25 high T-cell subset which was inversely related to T-cell proliferation (r = -0.54, p < 0.05) and to activation-induced release of TGF-β1 (r = -0.80, p < 0.001). The CD25 high T-cell subset tended to be impaired in the FH + group (% of CD3 + T cells: FH + , 5.1% vs. FH-, 12.6%), and notably, the FH + group showed a significantly reduced capacity for generation of both CD25 + (FH + , 16.2% vs. FH - , 34.9%; p < 0.01) and α + E T cells (FH + , 2.1% vs. FH - , 3.9%; p < 0.05). Our findings suggested that early-life exposure to a dietary antigen in the presence of LPS might modulate the immune system by generating T R cells. This capacity was impaired in neonates with hereditary allergy risk, but clinical follow-up will be required to determine a possible effect on allergy emergence.

One main hurdle to xenotransplantation, i.e. transplantation between different species, is the immunological barrier that the organ meets in the recipient. The aim of this thesis was to characterise xenogeneic rejection mechanisms by using the concordant mouse-to-rat heart transplantation model.Graft-infiltrating immune cells could be isolated from both rejecting and non-rejecting grafts using ex vivo propagation, a technique based on incubation of graft biopsies in culture medium for 48 hours. The numbers of recovered T lymphocytes were considerably higher in grafts undergoing cell-mediated rejection than in grafts undergoing acute vascular rejection (AVR) or in non-rejecting transplants. Thus, ex vivo propagation should be a valuable tool for further studies of cell-mediated rejection.Cytokine patterns in the grafts, as measured by a quantitative real-time RT-PCR method, showed that AVR and cell-mediated rejection are associated with an increase of both pro-inflammatory cytokines (IL-1β and TNF-α) and more specific cytokines (IL-2, IL-10, IL-12p40 and IFN-γ). These data differed considerably from the patterns seen in the spleens of the recipients. Cell-mediated xenograft rejection was also found to be associated with a local accumulation of hyaluronan.Oral administration of xenogeneic cells stimulated a production of antibodies that could induce hyperacute rejection of cardiac xenografts when passively transferred to graft recipients. This is in contrast to several models for autoimmune diseases and allogeneic transplantation where oral administration of antigens is an effective way to induce unresponsiveness. Hence, future attempts to induce oral tolerance in xenotransplantation should be done with caution.

BACKGROUND The aim of the present study was to further investigate the characteristics of both graft-infiltrating cells and splenocytes during acute vascular rejection (AVR), cell-mediated rejection and non-rejection of vascularized concordant xenografts, by analysing both proinflammatory [interleukin-1beta (IL-1beta) and tumour necrosis factor (TNF-alpha)] and more specific [(IL-2, IL-4, IL-10, IL-12p40 and interferon-gamma (IFN-gamma)] cytokines. A parallel investigation was made of the antibody response of IgM and IgG to the xenografts. METHODS Mouse hearts were heterotopically transplanted to the neck vessels of recipient rats. Grafts, spleens and sera were collected from untreated (AVR) and cyclosporin A (CyA) treated animals on day 2 after transplantation. Organs from rats treated with 15-deoxyspergualin (DSG) or CyA and DSG in combination were harvested on both day 2 and day 8. Grafts from DSG-treated rats undergo cell-mediated rejection and stop beating on day 9 and forth, while CyA + DSG treatment results in long-term graft survival. Real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was applied for analysis of intragraft and splenic cytokine messenger RNA (mRNA) expression. The phenotypes of the graft infiltrating cells were characterized by immunohistochemistry. The antibody response was investigated by means of immunofluorescence, haemagglutination and flow cytometry. RESULTS All the studied cytokines (IL-1beta, IL-2, IL-4, IL-10, IL-12p40, IFN-gamma and TNF-alpha) were up-regulated in the grafts from rejecting untreated (day 2) and DSG-treated animals (day 8) in comparison with grafts from CyA + DSG treated animals (day 8). On day 2 under immunosuppression with CyA, DSG or CyA + DSG no or low cytokine mRNA levels were found. The mRNA levels of IL-2, IL-4 and IFN-gamma in the spleens were suppressed under both DSG- and CyA + DSG treatment on day 8. Immunofluorescence showed deposits of both IgM and IgG in grafts from untreated, CyA-treated (day 2) and DSG-treated (day 8) animals, while CyA + DSG treatment diminished these deposits on both day 2 and day 8. No circulating antibodies were identified in either group. CONCLUSION We hereby conclude that both AVR on day 2 and cell-mediated rejection on day 8 (under DSG treatment) in a concordant cardiac mouse-to-rat xenotransplantation model are associated with an increase of proinflammatory cytokines, T helper 1 (Th1)-associated cytokines as well as IL-10, while immunosuppression with CyA + DSG diminishes the levels of all examined cytokines. Grafts undergoing AVR or cellular rejection are subjected to deposits of both IgM and IgG, although circulating donor specific antibodies are undetectable in serum.

Fe ´deration de Genetique et INSERM U458, Hoˆpital Robert-Debre (AP-HP), Paris, FranceWehaveanalyzedsurfactantproteinB(SP-B)and its encoding gene (SFTPB, MIM 178640)in 40 unrelated pediatric patients with un-explained respiratory distress (URD). Therewas high consanguinity (eight kindreds)and an underlying autosomal recessive traitcould be inferred in most cases, with overallhigh sex ratio (32/17) suggesting proband’sgendertoimpactonpenetrance.Theclinical/biological presentations fitted into threemajor nosologic frameworks. I: SP-B de-ficiency (nine probands), complete or in-complete, with homozygous/compoundlyheterozygous mutations identified (six pro-bands), including one from the populationisolate of Re´union Island (496delG). In ad-dition, there was a consanguineous kindredin which incomplete deficiency was unam-biguously unlinked to SFTPB. II: pulmonaryalveolar proteinosis (PAP, 19 probands),withtypicalstorageofPAS-positivematerialwithin the alveoli with foamy macrophagesandvariableinterstitialreaction,whichwasdiagnosed in most patients from Re´unionIsland. In contrast to previously publishedfindings, mutation and/or segregation ana-lyses excluded SFTPB as a disease locus,although slight metabolic derangementrelated to SP-B and/or mild SFTPB changescould somehow contribute to disease. III:URD without evidence for SP-B deficiencyor PAP (12 probands), equally unlinked toSFTPB, although a single patient had apossibly causal, maternally-derived, hetero-zygous genetic change (G4521A). The popu-lation frequency of five known and fournovel SNPs was studied, providing as manypotential markers for pulmonary diseaserelated to SFTPB. Overall, URD was foundto be heterogeneous, both phenotypicallyand genetically, even in population isolateswhere a founder effect might have beenexpected. When disease loci are identified,patient genotyping will be crucial as a diag-nostic aid, for devising proper treatment,and as a basis for genetic counseling.

OBJECTIVE: We seek to investigate socio-economic differences in psychiatric in-patient care regarding admission, treatment and outcome. METHOD: This study is undertaken on a comprehensive and exhaustive psychiatric case register of all psychiatric in-patient care carried out in Belgium in 1997 and 1998 (n=144 754). RESULTS: Lower socio-economic groups were more likely to be compulsorily admitted, to be cared for in a non-teaching or psychiatric hospital, to be admitted in a hospital with unexpectedly long average length of stay and to be admitted to a ward with a more severe case-mix. They were less likely to receive antidepressants and psychotherapies. The improvements in functioning and in symptoms were also less favourable for these groups. The lowest group had a higher risk of dying in the hospital. CONCLUSION: Psychiatric in-patient care is associated with moderate socio-economic differences in access, treatment and outcome. Further research is needed to clarify the causes of such disparities.

One main hurdle to xenotransplantation, i.e. transplantation between different species, is the immunological barrier that the organ meets in the recipient. The aim of this thesis was to characterise xenogeneic rejection mechanisms by using the concordant mouse-to-rat heart transplantation model.Graft-infiltrating immune cells could be isolated from both rejecting and non-rejecting grafts using ex vivo propagation, a technique based on incubation of graft biopsies in culture medium for 48 hours. The numbers of recovered T lymphocytes were considerably higher in grafts undergoing cell-mediated rejection than in grafts undergoing acute vascular rejection (AVR) or in non-rejecting transplants. Thus, ex vivo propagation should be a valuable tool for further studies of cell-mediated rejection.Cytokine patterns in the grafts, as measured by a quantitative real-time RT-PCR method, showed that AVR and cell-mediated rejection are associated with an increase of both pro-inflammatory cytokines (IL-1β and TNF-α) and more specific cytokines (IL-2, IL-10, IL-12p40 and IFN-γ). These data differed considerably from the patterns seen in the spleens of the recipients. Cell-mediated xenograft rejection was also found to be associated with a local accumulation of hyaluronan.Oral administration of xenogeneic cells stimulated a production of antibodies that could induce hyperacute rejection of cardiac xenografts when passively transferred to graft recipients. This is in contrast to several models for autoimmune diseases and allogeneic transplantation where oral administration of antigens is an effective way to induce unresponsiveness. Hence, future attempts to induce oral tolerance in xenotransplantation should be done with caution.