Immune reconstitution after haematopoietic cell transplantation in children: immunophenotype analysis with regard to factors affecting the speed of recovery

Immune reconstitution was studied prospectively in 66 children who underwent 77 haematopoietic cell transplantations (HCT): 46 autologous HCTs in 39 patients and 31 allogeneic HCTs in 27 patients. We studied the dynamic analysis of immune recovery with regard to potential factors affecting its speed, including age, type of HCT, diagnosis, graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection reactivation. Absolute counts of different lymphocyte subsets and immunoglobulin serum levels were determined in peripheral blood of patients on d -7 and +16, and then at various intervals up to 24 months post transplant. Common patterns of immune recovery after both allogeneic and autologous HCT were identified: (i) CD4+CD45RO+ peripheral T-cell expansion on d +16; (ii) inverted CD4+:CD8+ ratio from d +30 onwards; (iii) rapid natural killer (NK) cell (CD16+/-CD56+) count normalization. We observed prolonged T-cell lymphopenia (CD3+, CD3+CD4+, CD4+CD45RA+) until 24 months after autologous HCT, whereas in the allogeneic setting CD3+CD4+ cells, including naive CD45RA+ cells, returned to normal values at 9 months post transplant. Age > 10 years and coexistence of GvHD and CMV reactivation were associated with a substantial delay in T- (CD4+, including CD45RA+) and B-cell recovery after allogeneic HCT. Multidrug GvHD prophylaxis resulted in impaired T- (CD4+, CD4+CD45RA+) and B-cell reconstitution only in the early phase after allogeneic HCT (up to 4 months). Our results demonstrated that T-cell recovery was severely impaired in children after autologous HCT. It should be emphasized that specific approaches to enhance immune reconstitution are necessary to control minimal residual disease and avoid the risk of infectious complications in the autologous setting. Thymic involution after allogeneic HCT seems to be associated with age and coexistence of GvHD and CMV reactivation.     

Dermatosis bullosa in patient with chronic renal failure under hemodialysis treatment--case report

A case of 45-year-old patient with chronic renal failure treated by hemodialysis associated with skin changes typical for porphyria cutanea tarda is reported. The diagnosis was based on clinical manifestations and on histopathologic examination of the skin segment. The skin was low sensitive for UVA rays, serum levels of aluminium and lead were significantly elevated. We did not find porphyrins in the urine (24-hour collection 100 ml) as well as in the dialysis fluid.     

Convergence of the adhesive and fibrinolytic systems: recognition of urokinase by integrin alpha Mbeta 2 as well as by the urokinase receptor regulates cell adhesion and migration

Previous studies demonstrated that integrin alpha(M)beta(2) (CD11b/18, Mac-1) forms a physical complex with the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes. In this study, we used human peripheral blood neutrophils and transfected cells expressing alpha(M)beta(2), uPAR, or both receptors to show that the integrin can directly interact with urokinase (uPA). We demonstrate that alpha(M)beta(2) supported adhesion and migration of these cells to uPA, and, in each case, blockade of alpha(M)beta(2) suppressed the response. Within uPA, both the kringle and proteolytic domains are recognized by alpha(M)beta(2), which are distinct from the growth factor domain that binds to uPAR. Within the alpha(M) subunit of the integrin, the I domain interacts with uPA, which is distinct from the region that interacts with uPAR. On cells expressing uPAR and alpha(M)beta(2), both receptors mediated adhesion and migration. This cooperation was particularly apparent in the responses of neutrophils to uPA, where blockade of alpha(M)beta(2) reduced uPAR-mediated responses and engagement of uPAR enhanced recognition of uPA by alpha(M)beta(2). Thus, recognition of uPA by alpha(M)beta(2) allows for formation of a multicontact trimolecular complex, in which a single uPA ligand may bind simultaneously to both uPAR and alpha(M)beta(2). This complex may play an important role in the control of inflammatory cell migration and vascular homeostasis.     

Evaluation of a risk of a cross-reactivity with Echinococcus multilocularis-specific Em2plus antigen in patients with liver cancer

The incidence of non-specific reactions with E. multilocularis antigen in patients with liver malignancies, and the risk of a supradiagnosis of alveolar echinococcosis (AE) in space-occupying lesions in the liver due to neoplastic proliferative diseases were studied. Analysis of specific IgG serum antibody against Em2plus antigenic complex was performed in 11 AE patients in comparison to 76 individuals with malignant neoplasms of abdominal or extra-hepatic location, including some patients with primary hepatocellular cancer or distant metastases to liver, and 42 patients with benign hepatic lesions. Only one false borderline result was reported in a case with colorectal cancer, and dissemination to liver. Low risk of false positive results with E. multilocularis-specific Em2plus antigen in patients with liver malignancies makes the test valuable for practical reasons in a differential diagnosis of irregular tumor masses visualized by imaging techniques.     

Vaspin (but not neuropeptide B or neuropeptide W) as a possible predictor of body weight normalization in anorexia nervosa

IntroductionThe aim of the study was to evaluate the correlation between the nutritional status of patients with anorexia nervosa (AN) and levels of vaspin (VASP), neuropeptide B (NPB), neuropeptide W (NPW) and total antioxidant status (TAS).Material and methodsNinety serum samples collected from 30 teenage female patients during the acute stage of AN and 30 healthy persons (CONTR) were subjected to biochemical analysis; patients with AN were examined at the beginning of the study (AN-I) and after hospitalization (AN-II), as a result of which partial stabilization of anthropometric measurements was achieved (an increase of body mass index (BMI) by 3.5 kg/m²).ResultsVaspin levels dropped at the end of the hospitalization (compared to AN-I, p < 0.05), achieving values comparable to the CONTR; moreover there was a positive correlation between VASP level and the achieved body weight in AN-II (p < 0.05). Positive correlations were also noted with regard to VASP vs. NPB in AN-I (p < 0.02) (and AN-II, p < 0.013), as well as in the case of VASP vs. NPW in the same groups (p < 0.02 and p < 0.015, respectively). NPB concentration was higher in AN-I (p < 0.05) and AN-II (p < 0.018) than in CONTR, whereas there were no differences (p > 0.05) with regard to levels of VASP, NPW, or TAS.ConclusionsThe high level of NPB despite treatment and normalization of VASP level may suggest that there are chronic neuroendocrine disorders at play in anorexia nervosa.     

Differentiation and proliferation of periosteal osteoblast progenitors are differentially regulated by estrogens and intermittent parathyroid hormone administration

The periosteum is now widely recognized as a homeostatic and therapeutic target for actions of sex steroids and intermittent PTH administration. The mechanisms by which estrogens suppress but PTH promotes periosteal expansion are not known. In this report, we show that intermittent PTH(1-34) promotes differentiation of periosteal osteoblast precursors as evidenced by the stimulation of the expression or activity of alkaline phosphatase as well as of targets of the bone morphogenetic protein 2 (BMP-2) and Wnt pathways. In contrast, 17beta-estradiol (E2) had no effect by itself. However, it attenuated PTH- or BMP-2-induced differentiation of primary periosteal osteoblast progenitors. Administration of intermittent PTH to ovariectomized mice induced rapid phosphorylation of the BMP-2 target Smad1/5/8 in the periosteum. A replacement dose of E2 had no effect by itself but suppressed PTH-induced phosphorylation of Smad1/5/8. In contrast to its effects to stimulate periosteal osteoblast differentiation, PTH promoted and subsequently suppressed proliferation of periosteal osteoblast progenitors in vitro and in vivo. E2 promoted proliferation and attenuated the antiproliferative effect of PTH. Both hormones protected periosteal osteoblasts from apoptosis induced by various proapoptotic agents. These observations suggest that the different effects of PTH and estrogens on the periosteum result from opposing actions on the recruitment of early periosteal osteoblast progenitors. Intermittent PTH promotes osteoblast differentiation from periosteum-derived mesenchymal progenitors through ERK-, BMP-, and Wnt-dependent signaling pathways. Estrogens promote proliferation of early osteoblast progenitors but inhibit their differentiation by osteogenic agents such as PTH or BMP-2.     

Relative bioavailability and antioxidant potential of two coenzyme q10 preparations

Coenzyme Q10 (CoQ10) is synthesized by the human body and found in certain foods. Daily supplementation of CoQ10 could protect against heart disease but the bioavailability of CoQ10 supplements depends on the formulation taken. We compared the bioavailability and antioxidant properties of two commercial CoQ10 formulations, a commercial grade CoQ10 powder (commercial grade CoQ) and a new BT-CoQ10 BIO-TRANSFORMED (BT-CoQ10) obtained by fermentation of a soy-based, CoQ10-rich media with baker's yeast. Eleven healthy individuals participated in a randomized two-way crossover trial, with a 3-week washout period. Capsules containing 300 mg of either BT-CoQ10 or commercial grade CoQ10 were given daily for 1 week and multiple blood samples were taken for CoQ10, glutathione and glutathione peroxidase (GPx) determination. In 3 subjects, baseline plasma CoQ10 levels were lower prior to BT than prior to commercial grade CoQ treatment. In the remaining participants, ingestion of BT vs. commercial grade CoQ significantly increased maximum plasma CoQ10 concentration (+126%, p = 0.04) and tended to increase CoQ10 area under the curve from 0 to 24 h (+160%, p = 0.07). One week of treatment with each formulation increased plasma CoQ10 but did not alter plasma glutathione or GPx activity. The enhanced bioavailability of the BT product might be due to its predominantly reduced, hydrophilic membrane-complex form.