HLA-DO increases bacterial superantigen binding to human MHC molecules by inhibiting dissociation of class II-associated invariant chain peptides

HLA-DO (H2-O in mice) is an intracellular non-classical MHC class II molecule (MHCII). It forms a stable complex with HLA-DM (H2-M in mice) and shapes the MHC class II-associated peptide repertoire. Here, we tested the impact of HLA-DO and H2-O on the binding of superantigens (SAgs), which has been shown previously to be sensitive to the structural nature of the class II-bound peptides. We found that the binding of staphylococcal enterotoxin (SE) A and B, as well as toxic shock syndrome toxin 1 (TSST-1), was similar on the HLA-DO⁺ human B cell lines 721.45 and its HLA-DO⁻ counterpart. However, overexpressing HLA-DO in MHC class II⁺ HeLa cells (HeLa-CIITA-DO) improved binding of SEA and TSST-1. Accordingly, knocking down HLA-DO expression using specific siRNAs decreased SEA and TSST-1 binding. We tested directly the impact of the class II-associated invariant chain peptide (CLIP), which dissociation from MHC class II molecules is inhibited by overexpressed HLA-DO. Loading of synthetic CLIP on HLA-DR⁺ cells increased SEA and TSST-1 binding. Accordingly, knocking down HLA-DM had a similar effect. In mice, H2-O deficiency had no impact on SAgs binding to isolated splenocytes. Altogether, our results demonstrate that the sensitivity of SAgs to the MHCII–associated peptide has physiological basis and that the effect of HLA-DO on SEA and TSST-1 is mediated through the inhibition of CLIP release.     

Immunoglobulin G from Breast Cancer Patients Regulates MCF-7 Cells Migration and MMP-9 Activity by Stimulating Muscarinic Acetylcholine Receptors

Purpose

We have previously reported the expression of muscarinic acetylcholine receptors (mAChR) in human breast tumors. The activation of these receptors triggered tumor cell proliferation. Considering that invasion and metastasis is the major cause of death in cancer, we investigated the action of autoantibodies against mAChR derived from breast cancer patients in stage I (T1N0Mx-IgG) on MCF-7 cells migration and metalloproteinase-9 (MMP-9) activity. We also analyzed the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.

Methods

Immunoglobulin G (IgG) was purified by chromatography in protein G-agarose from blood samples of breast cancer patients obtained under informed consent. Migration was assayed by an in vitro wound assay. MMP-9 activity was quantified by zymography.

Results

T1N0Mx-IgG promoted tumor cell migration and increased MMP9 activity mimicking the action of the muscarinic agonist carbachol. This effect was reduced not only by the presence of atropine but also by 4-DAMP or tropicamide, antagonists for M₃ and M₄ mAChR subtypes respectively. The actions of T1N0Mx-IgG and carbachol on MCF-7 cells, involved the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.

Conclusions

IgG from breast cancer patients in stage I could be promoting tumor progression by regulating migration and MMP-9 activity in tumor cells via mAChR activation. The presence of these autoantibodies could be determining the prognosis of breast cancer in these patients.     

Computed tomographic scan mapping of gastric wall perfusion and clinical implications

Background

Several postoperative gastrointestinal complications are attributed to ischemia. We herein evaluate the gastric wall perfusion using computed tomography (CT) scan perfusion index on trial to address the etiology of ischemic complication after sleeve gastrectomy.

Methods

A retrospective study of 205 patients undergoing CT scan of the abdomen to evaluate the pattern of gastric vascular perfusion was performed. The perfusion index of the gastric mucosa was measured at 5 gastric points using CT perfusion scanning.

Results

Gastric perfusion at the angle of His (AOH) (53.51 ± 14.38) was statistically significantly lower (P < .001) than that at the other gastric points studied: fundus, greater curvature, lesser curvature, incisura angularis, and mid gastric points (76.16 ± 15.21, 73.27 ± 16.55, 76.12 ± 16.12, and 75.24 ± 14.9, respectively). Gastric perfusion was significantly lower at all the gastric points (and especially so at the AOH) among obese patients (33 cases) compared with nonobese patients (18 cases). Gastric perfusion at all the points studied showed a decrease as the body mass index increases. Hypertensive patients had a better gastric perfusion compared with nonhypertensive patients.

Conclusions

Gastric wall perfusion is statistically significantly decreased at the AOH and gastric fundus compared with perfusion at other gastric points. Gastric perfusion at all the gastric points studied decreased with the increase in body mass index. Gastric leakage in obese patients following sleeve gastrectomy could be attributed to a decrease in the blood supply at AOH.     

Independent risk factors for early urologic complications after kidney transplantation

Urologic complications are the most frequent technical adverse events following kidney transplantation (KTX). We evaluated traditional and novel potential risk factors for urologic complications following KTX. Consecutive KTX recipients between December 1, 2006 and December 31, 2010 with at least six‐month follow‐up (n = 635) were evaluated for overall urologic complications accounting for donor, recipient, and transplant characteristics using univariate and multivariate logistic regression. Urologic complications occurred in 29 cases (4.6%) at a median of 40 d (range 1–999) post‐transplantation and included 17 ureteral strictures (2.6%), five (0.8%) ureteral obstructions due to donor‐derived stones or intraluminal thrombus, and seven urine leaks (1.1%). All except two complications occurred within the first year of transplantation. Risk factors for urologic complications on univariate analysis were dual KTX (p = 0.04) and renal artery multiplicity (p = 0.02). On multivariate analysis, only renal artery multiplicity remained significant (aHR 2.4, 95% confidence interval 1.1, 5.1, p = 0.02). Donation after cardiac death, non‐mandatory national share kidneys, donor peak serum creatinine > 1.5 mg/dL or creatinine phosphokinase > 1000 IU/L, and donor down time were not associated with urologic complications. Our data suggest that donor artery multiplicity is an independent risk factor for urologic complications following KTX.     

Digestive bleeding and acute abdomen caused by jejunal diverticulosis. Case report

We present a patient with acute abdomen and digestive bleeding caused by jejunal diverticulosis. Jejunal diverticulosis, mainly asymptomatic, when is symptomatic have a wide clinical spectrum, ranging from chronic anemic syndrome to acute abdomen. In this communication, we reviewed the clinical presentation, the pathogenesis and the treatment this infrequent pathology.