Galectin-3 deficiency enhances type 2 immune cell-mediated myocarditis in mice

Experimental autoimmune myocarditis (EAM) is a mouse model of immune-mediated myocarditis and cardiomyopathy. The role of Galectin-3 (Gal-3), a β-galactoside-binding lectin, in autoimmune myocarditis has not been studied. Therefore, the aim of this study was to delineate the role of Gal-3 in myosin peptide-induced autoimmune myocarditis in mice. EAM was induced in relatively resistant C57BL/6J mice (wild type, WT) and in mice with a targeted deletion of Gal-3 gene (Gal-3KO) by immunization with myosin peptide MyHCα_334–352. Gal-3KO mice developed more severe myocarditis and more pronounced heart hypertrophy than WT mice. Increased infiltration of CD45⁺ leucocytes, CD3⁺ T cells, F4/80⁺ macrophages, and eosinophils was observed in hearts of Gal-3KO mice compared to WT mice on day 21 after EAM induction. Moreover, hearts of Gal-3KO mice had more T helper type 2 (Th2) cells, alternatively activated M2 macrophages, higher amounts of IgG deposits, and higher serum levels of IL-4 and IL-33 than WT mice. Ablation of Gal-3 in Th1-dominant C57BL/6J mice that are relatively resistant to EAM resulted in more severe disease characterized by type 2 cardiac inflammation. The complex effects of Gal-3 on EAM progression might be important in the consideration of therapeutic options for the treatment of EAM.     

The influence of RGD-bearing hydrogels on the re-expression of contractile vascular smooth muscle cell phenotype

This study reports on the ability of poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds with pendant integrin-binding GRGDSP peptides (RGD-gels) to support the re-differentiation of cultured vascular smooth muscle cells (SMCs) toward a contractile phenotype. Human coronary artery SMCs were seeded on RGD-gels, hydrogels with other extracellular matrix derived peptides, fibronectin (FN) and laminin (LN). Differentiation was induced on RGD-gels with low serum medium containing soluble heparin, and the differentiation status was monitored by mRNA expression, protein expression, and intracellular protein organization of the contractile smooth muscle markers, smooth muscle α-actin, calponin, and SM-22α. RGD-gels supported a rapid induction (2.7- to 25-fold up-regulation) of SMC marker gene mRNA, with expression levels that were equivalent to FN and LN controls. Marker protein levels mirrored the changes in mRNA expression, with levels on RGD-gels indistinguishable from FN and LN controls. Furthermore, these markers co-localized in stress fibers within SMCs on RGD-gels suggesting the recapitulation of a contractile apparatus within the cells. These results indicate that SMCs cultured on RGD-bearing hydrogels can re-differentiate toward a contractile phenotype suggesting this material is an excellent candidate for further development as a bioactive scaffold that regulates SMC phenotype.     

Potential Function of Granulysin,Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection

Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy.Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9⁺Vδ2⁺ T cells, CD4⁺ T cells and CD8⁺ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection.Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry.Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8⁺ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed.Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection.     

Harnessing innovative technologies to advance children's mental health: Behavioral parent training as an example

Disruptive behaviors of childhood are among the most common reasons for referral of children to mental health professionals. Behavioral parent training (BPT) is the most efficacious intervention for these problem behaviors, yet BPT is substantially underutilized beyond university research and clinic settings. With the aim of addressing this research-to-practice gap, this article highlights the considerable, but largely unrealized, potential for technology to overcome the two most pressing challenges hindering the diffusion of BPT: (1). The dearth of BPT training and supervision opportunities for therapists who work with families of children with disruptive behaviors; and (2). The failure to engage and retain families in BPT services when services are available. To this end, this review presents a theoretical framework to guide technological innovations in BPT and highlights examples of how technology is currently being harnessed to overcome these challenges. This review also discusses recommendations for using technology as a delivery vehicle to further advance the field of BPT and the potential implications of technological innovations in BPT for other areas of children's mental health are discussed.     

Serodiagnosis of tuberculosis and leprosy by enzyme immunoassay

Objective: To evaluate the use of serodiagnosis for tuberculosis and leprosy using mycobacterial antigen 38 kDa, with kits from Omega laboratories, to detect IgG by enzyme immunoassay (EIA).
Method: The study population consisted of 58 patients with evidence of tuberculous infection (culture of Mycobacterium tuberculosis complex or microscopic evidence), of whom 23 had pulmonary and 35 had extrapulmonary disease. There were six subjects who had recently been treated for tuberculosis, 11 patients on treatment for leprosy and 137 patients suspected of having tuberculosis on clinical or radiologic grounds (without laboratory evidence). A control group comprised 35 healthy individuals or patients suffering from diseases other than tuberculosis.
Results: The tests showed that there was a significant difference in antibody levels between the patients with active pulmonary disease, extrapulmonary tuberculosis and leprosy in comparison with the control group ( p <0.001). The sensitivities of the two tests together for proven pulmonary tuberculosis were 100% and 95.7% at 1.0–1.5 and >1.6 EIA cut-off points respectively, while the specificities were 88.5% and 100% at the same cut-off points. The sensitivities for extrapulmonary tuberculosis were 71.4% and only 51.4% at 1.0–1.5 and >1.6 EIA cut-off points. The test was positive in 30 (21.9%) of the 137 suspected patients, while 43 (31.4%) had an equivocal result and the remaining 64 (47.7%) suspects were definitely negative. There was again a significant difference in positivity rates between suspects and the control group.
Conclusions: Omega IgG test is useful in the serodiagnosis of active pulmonary tuberculosis and leprosy, but less sensitive in extrapulmonary disease, particularly in children. Equivocal results may only add to the evidence of tuberculosis in early or minimal disease.     

T-cell acute lymphoblastic leukemia in a child with ataxia-telangiectasia: case report

We present a patient with acute lymphoblastic leukemia and ataxia-telangiectasia (A-T). The 4-year-old girl is the first child of young nonconsanguineous parents of Serbian origin. Gait problems appearing in the second year of life were treated by physiotherapy. At the age of 4 she was diagnosed with T-cell acute lymphoblastic leukemia and treated according to Berlin-Frankfurt-Munster strategy. Owing to typhlitis developing after 15 days of cytotoxic treatment, frequent radiologic examinations were performed causing profound aplasia. Typhlitis did not respond to conservative treatment but necessitated extensive bowel resection. At that time the A-T was suspected by our team and confirmed by increased chromosomal radiosensitivity and markedly reduced level of A-T mutated protein. Chemotherapy was continued without alkylating agents and further radiologic imaging ran an uncomplicated course. At present, the patient is in first remission and 2.5 years since the beginning of the treatment. We stress the importance of careful initial neurologic evaluation of children with malignancy.     

Ruptured intramural intestinal hematoma in an adolescent patient with severe hemophilia A

We report on a 17-year-old patient with severe hemophilia A without inhibitors who developed abdominal bleeding after an episode of severe cough. Abdominal ultrasound showed intramural intestinal hematoma as well as large amount of peritoneal fluid appearing as blood and right hematocele. Abdominal CT revealed markedly thickened intestinal wall in sigmoidal region. Patient was managed with replacement therapy as well as peritoneal drainage with favorable outcome. This is the first report on a hematoperitoneum in a hemophiliac due to ruptured intramural sigmoidal hematoma.     

Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.