Chemokines and their receptors control the emigration of leukocytes during inflammation. The role of the RANTES (regulated on activation normal T-cell expressed and secreted) receptors CCR1 and CCR5 in the selective recruitment of monocytes, T(H)1-like T-cell clones, and peripheral T cells enriched for CD45RO(+) "memory" cells were tested in a system in which arrest under flow conditions is triggered by RANTES immobilized to activated endothelium. With the use of selective nonpeptide receptor antagonists or blocking antibodies, it was found that the RANTES-induced arrest of these cells was mediated predominantly by CCR1. In contrast, CCR5 mainly contributed to the spreading in shear flow, and both CCR1 and CCR5 supported transendothelial chemotaxis toward RANTES. The data in this study reveal specialized roles of apparently redundant receptors in distinct steps of leukocyte trafficking and suggest that not all receptors currently used to define mononuclear cell subsets are involved in their direct recruitment from the circulation.

With the unprecedented developments in deep learning, automatic segmentation of main abdominal organs (i.e., liver, kidney, and spleen) seems to be a solved problem as the state-of-the-art (SOTA) methods have achieved comparable results with inter-observer variability on existing benchmark datasets. However, most of the existing abdominal organ segmentation benchmark datasets only contain single-center, single-phase, single-vendor, or single-disease cases, thus, it is unclear whether the excellent performance can generalize on more diverse datasets. In this paper, we present a large and diverse abdominal CT organ segmentation dataset, termed as AbdomenCT-1K, with more than 1000 (1K) CT scans from 11 countries, including multi-center, multi-phase, multi-vendor, and multi-disease cases. Furthermore, we conduct a large-scale study for liver, kidney, spleen, and pancreas segmentation, as well as reveal the unsolved segmentation problems of the SOTA method, such as the limited generalization ability on distinct medical centers, phases, and unseen diseases. To advance the unsolved problems, we build four organ segmentation benchmarks for fully supervised, semi-supervised, weakly supervised, and continual learning, which are currently challenging and active research topics. Accordingly, we develop a simple and effective method for each benchmark, which can be used as out-of-the-box methods and strong baselines. We believe the introduction of the AbdomenCT-1K dataset will promote the future in-depth research towards clinical applicable abdominal organ segmentation methods. Moreover, the datasets, codes and trained models of baseline methods will be publicly available.

Several microbes have been suspected as pathogenetic factors in schizophrenia. We have previously observed increased frequencies of chlamydial infections and of human lymphocyte antigen (HLA)-A10 in independent studies of schizophrenia. Our aim here was to analyze frequencies of three types of Chlamydiaceae in schizophrenic patients (n = 72), random controls (n = 225) and hospital-patient controls (n = 36), together with HLA-A genotypes. Patients were diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders-IV. Blood samples were collected at the beginning of hospitalization and analyzed with Chlamydiaceae species-specific polymerase chain reaction (PCR). Control panels consisted of randomly selected volunteers and hospitalized, non-schizophrenic patients. We found chlamydial infection in 40.3% of the schizophrenic patients compared to 6.7% in the controls. The association of schizophrenia with Chlamydiaceae infections was highly significant (P = 1.39 Â 10 À10 , odds ratio (OR) = 9.43), especially with Chlamydophila psittaci (P = 2.81 Â 10 À7, OR = 24.39). Schizophrenic carriers of the HLA-A10 genotype were clearly most often infected with Chlamydophila, especially C. psittaci (P = 8.03 Â 10 À5 , OR = 50.00). Chlamydophila infections represent the highest risk factor yet found to be associated with schizophrenia. This risk is even further enhanced in carriers of the HLA-A10 genotype.

Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism of the immunoproteasome subunits LMP2 and LMP7 and of the transporters associated with antigen processing (TAP1 and TAP2) in two independently collected panels of colorectal carcinoma patients (N 1 ¼ 112, N 2 ¼ 62; controls, N ¼ 165). High risk of colon cancer was associated with the LMP7-K/Q genotype (OR ¼ 8.10, P ¼ 1.10 Â 10 À11) and low risk with the LMP7-Q/Q genotype (OR ¼ 0.10, P ¼ 5.97 Â 10 -13 ). The basis for these distinct associations of LMP7 genotypes was functionally assessed by IFN-g stimulation of colon carcinoma cell lines (N ¼ 10), followed by analyses of mRNA expression of HLA class I, TAP1, TAP2, and LMP7, with real-time PCR. Whereas induction of HLA-B, TAP1, and TAP2 was comparable in all cell lines, transcript amounts of LMP7-Q increased 10-fold, but of LMP7-K only 3.8-fold. This correlated with a reduced transcript stability of LMP7-K (t1 2 % 7 minutes) compared with LMP7-Q (t1 2 % 33 minutes). In addition, LMP7-Q/Q colon carcinoma cells increased (the peptide based) HLA class I surface expression significantly after IFN-g stimulation, whereas LMP7-Q/K and LMP7-K/K carcinoma cells showed minimal (<20%) changes. These results suggest that the presence of LMP7-K can reduce the formation of immunoproteasomes and thus peptide processing, followed by reduced peptide-HLA presentation, a crucial factor in the immune response against cancer. Cancer Res; 71(23); 7145-54. Ó2011 AACR.

The viral CC chemokine macrophage inhibitory protein-II (vMIP-II) encoded by human herpes virus 8 (HHV-8) binds to multiple chemokine receptors, however, its ability to control the initial recruitment of specific leukocyte subtypes from the peripheral circulation has not been fully clarified. Here we show that vMIP-II blocks the firm arrest and transmigration of monocytes or Th1-like T lymphocytes triggered by RANTES immobilized on activated human microvascular endothelium (HMVEC) under flow conditions. The internalization of the receptors CCR1 and CCR5 that mediate arrest and transmigration of these cells in response to RANTES was prevented by vMIP-II, supporting its role as an antagonist of CCR1 and CCR5. In contrast, vMIP-II triggered the firm arrest of eosinophils and Th2-like T cells by engaging CCR3, as confirmed by its down-regulation. Immunohistochemical analysis of HHV-8-associated Kaposi's sarcoma lesions marked by vMIP-II expression and mononuclear cell infiltration revealed a predominance of Th2-type CCR3(+) lymphocytes over Th1-type CXCR3(+)/CCR5(+) leukocytes, indicating that as a CCR3 agonist vMIP-II can drive a Th2-type immune response in vivo. Thus, our data provide evidence for a immunomodulatory role of vMIP-II in directing inflammatory cell recruitment away from a Th1-type towards a Th2-type response and thereby facilitating evasion from cytotoxic reactions.