B-cell recovery after stem cell transplantation of Artemis-deficient SCID requires elimination of autologous bone marrow precursor-B-cells

Severe combined immunodeficiencies (SCID) are commonly fatal early in life. Adequate diagnosis and rapid institution of treatment, such as allogeneic stem cell transplantation (SCT), is essential. Several studies demonstrated that reconstitution of B-cell function after SCT is better in B-positive SCID than in B-negative SCID. We demonstrate that B-cell reconstitution in a B-negative SCID patient due to an Artemis mutation required the elimination of the autologous precursor-B-cells in bone marrow, probably to create physical space in the precursor-B-cell niches. Apparently, occupation of the precursor-B-cell niches is a potential dominant factor influencing repopulation of a functional B-cell compartment in B-negative SCID.     

Human umbilical vein versus heparin-bonded polyester for femoro-popliteal bypass: 5-year results of a prospective randomized multicentre trial.

PURPOSE: To compare long-term patency of Heparin-Bonded Dacron (HBD) and Human Umbilical Vein (HUV) vascular prostheses in above-knee femoro-popliteal bypass surgery. DESIGN: A prospective randomized multi-centre clinical trial. PATIENTS AND METHODS: Femoro-popliteal bypasses were performed in 129 patients between 1996 and 2001. After randomization 70 patients received an HUV and 59 an HBD prosthesis. Patients were followed up every three months during the first postoperative year and yearly thereafter. The median follow-up was 60 months (range 3-96 months). Graft occlusions were detected by duplex scanning, angiography or surgical exploration. RESULTS: The cumulative primary patency rates were 79%, 66% and 58% at 1, 3 and 5 years postoperatively. Primary patency rates for HUV were 74%, 64% and 58% at 1, 3 and 5 years and 84%, 68% and 58% for HBD, respectively (log-rank test, p=0.745). Overall secondary patency rates were 82%, 72% and 61% at 1, 3 and 5 years postoperatively. The overall cumulative limb salvage at 5 years follow-up was 89% (CI 80%-91%) and was not dependent on graft type. Smoking (p=0.019), number of patent crural arteries (p=0.030) and previous cerebro-vascular events (p=0.030) were significant predictors of graft occlusion. CONCLUSION: There was no difference in long-term graft performance between HUV and HBD for above knee infrainguinal bypass.     

A single split-signal FISH probe set allows detection of TAL1 translocations as well as SIL-TAL1 fusion genes in a single test.

About 30% of T cell acute lymphoblastic leukemias (T-ALL) carry TAL1 gene aberrations. In the majority of cases (approximately 25%), this concerns a submicroscopic deletion of approximately 90 kb in chromosome region 1p32, which deletes the coding regions of the SIL gene and the untranslated region of the TAL1 gene, thereby placing the TAL1 gene under control of the SIL promoter region. Translocation (1;14)(p32;q11) involving the TAL1 gene occurs at a much lower frequency (3%), whereas some other rare variant translocations have been described as well. In this study we developed a set of TAL1 FISH probes based on the split-signal FISH principle that enables detection of both types of TAL1 gene aberrations in single test. For this purpose, one probe was designed downstream of the TAL1 gene (TAL1-D) and the second probe in the region upstream of the TAL1 gene, partly covering the SIL gene (SIL-U). We show that this split-signal FISH probe set allows reliable detection of the unaffected SIL-TAL1 gene region with a fusion signal, SIL-TAL1 fusion genes with loss of the SIL-U signal, and TAL1 gene translocations with a split-signal, independent of the involved partner gene.     

Long-term results of surgical treatment for pulmonary valve stenosis

109 children who survived surgical treatment for isolated pulmonary valve stenosis were followed for up to 17 years. In all the postoperative status was assessed as satisfactory. Cardiac catheterization repeated in 43 gave a resting valve gradient below 40 mmHg. The 22 children whose pulmonary valves had been excised were as healthy as the 87 who had undergone pulmonary valvotomy. Consideration was given to the desirable length of postoperative review. Except for the few children with symptoms before operation, a postoperative increase in exercise tolerance was not a feature.     

The European Common Agricultural Policy on fruits and vegetables: exploring potential health gain from reform

BACKGROUND: Consumption of fruits and vegetables is associated with a reduced risk of cardiovascular disease and cancer. The European Union Common Agricultural Policy keeps prices high by limiting the availability of fruits and vegetables. This policy is at odds with public health interests. We assess the potential health gain for the Dutch population of discontinuing EU withdrawal support for fruits and vegetables. METHODS: The maximum effect of the reform was estimated by assuming that a quantity equivalent to the amount of produce withdrawn in recent years would be brought onto the market. For the calculation of the effect of consumption change on health we constructed a multi-state life table model in which consumption of fruits and vegetables is linked to ischaemic heart disease, stroke, and cancer of the oesophagus, stomach, colorectum, lung and breast. Uncertainty is quantified using Monte Carlo simulation. RESULTS: The reform would maximally increase the average consumption of fruits and vegetables by 1.80% (95% uncertainty interval 1.12-2.73), with an ensuing increase in life expectancy of 3.8 (2.2-5.9) days for men and 2.6 (1.5-4.2) days for women. The reform is also likely to decrease socio-economic inequalities in health. CONCLUSION: Ending EU withdrawal support for fruits and vegetables could result in a modest health gain for the Dutch population, though uncertainty in the estimates is high. A more comprehensive examination of the health effects of the EU agricultural policy could help to ensure health is duly considered in decision-making.     

Evidence that urocortin I acts as a neurohormone to stimulate alpha MSH release in the toad Xenopus laevis

We have raised the hypothesis that in the South African clawed toad Xenopus laevis, urocortin 1 (UCN1), a member of the corticotropin-releasing factor (CRF) peptide family, functions not only within the brain as a neurotransmitter/neuromodulator but also as a neurohormone, promoting the release of alpha-melanophore-stimulating hormone (alphaMSH) from the neuroendocrine melanotrope cells in the intermediate lobe of the pituitary gland. This hypothesis has been investigated by (1) assessing the distribution of UCN1 and CRF by light immunocytochemistry, (2) determining the subcellular presence of UCN1 in the neural lobe of the pituitary gland by immuno-electron microscopy applying high-pressure freezing and cryosubstitution, and (3) testing the effect of UCN1 on MSH release from toad melanotrope cells using in vitro superfusion. In the X. laevis brain, the main site of UCN1-positive somata was found to be the Edinger-Westphal nucleus. UCN1 immunoreactivity (ir) also occurs in the nucleus posteroventralis tegmenti, central gray, nucleus reticularis medius, nucleus motorius nervi facialis, and nucleus motorius nervi vagi. UCN1 occurs together with CRF in the nucleus motorius nervi trigemini, and in the magnocellular nucleus, which send a UCN1- and CRF-containing fiber tract to the median eminence. Strong UCN1-ir and CRF-ir were found in the external zone of the median eminence. From the internal zone of the median eminence, UCN1-ir fibers, but few CRF-ir fibers, were found to project to the pituitary neural lobe, where they form numerous neurohemal axon terminals. Ultrastructurally, two types of terminal containing UCN1-ir secretory granules were distinguished: type A contains large, moderately electron-dense, round secretory granules and type B is filled with smaller, strongly electron-dense, ellipsoid secretory granules. In vitro superfusion studies showed that UCN1 stimulated the release of alphaMSH from melanotrope cells in a dose-dependent manner. Our results support the hypothesis that in X. laevis, UCN1 released from neurohemal axon terminals in the pituitary neural lobe functions as a stimulatory neurohormone for alphaMSH release from melanotrope cells of the pituitary intermediate lobe.     

(-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity

Green tea polyphenols have been shown to inhibit cancer in a variety of tumor models, including ultraviolet B (UVB)-induced non-melanoma skin cancer. In green tea extracts, the major dry mass constituent is the family of catechins, of which (-)-epigallocatechin-(3)-gallate (EGCG) is considered to be important for the chemopreventive activity. EGCG has been shown to have antioxidant properties, but there has been little progress toward identifying the specific targets and mechanisms of its action. Using cultured human keratinocytes, we show that UVB- induced AP-1 activity is inhibited by EGCG in a dose range of 5.45 nM to 54.5 microM. EGCG is effective at inhibiting AP-1 activity when applied before, after or both before and after UVB irradiation. EGCG also inhibits AP-1 activity in the epidermis of a transgenic mouse model. This work begins to define a mechanism by which EGCG could be acting to inhibit UVB-induced tumor formation.      

Glucocorticoid receptor and heat shock protein 90 in peripheral blood mononuclear cells from asthmatics

目的探讨糖皮质激素受体(GR)和热休克蛋白90(HSP90)mRNA在糖皮质激素敏感型(SS)、依赖型(SD) 和抵抗型(SR)哮喘中的表达及其在SR哮喘发病中的作用。 方法采用反转录-聚合酶链(RT-PCR)的方法分别测定正常人(10例)、SS哮喘(10例)、SD哮喘(5例)和 SR哮喘(6例)的外周血单个核细胞(PBMC)中GR mRNA和HSP90 mRNA的表达,并在体外用IL-2、IL-4分 别、联合刺激上述细胞观察其受刺激后GR mRNA和HSP90 mRNA表达的改变情况。 结果 SR哮喘的GR和HSP90 mRNA表达水平最高(分别为0.730±0.171和1.122±0.165),SS哮喘次之 (分别为0.359±0.350和0.885±0.250),SD哮喘最低(分别为0.017±0.008和0.078±0.039)。正常人有 一定表达(分别为0.052±0.013和0.362±0.101)。GR和HSP90 mRNA的表达各组间相比P＜0.05。正 常人、SS、SD和SR哮喘HSP90/GR的比值分别为7.15±1.84、8.39±7.95、5.51±3.30、1.57±0.18,SR哮喘 HSP90/GR比值明显低于前三组(P＜0.05)。IL-2和IL-4单独刺激对SS、SD和SR哮喘的GR、HSP90 mRNA表达无明显影响,二者联合刺激可使SS、SD和SR哮喘GR mRNA表达以及SS、SD哮喘HSP90 mRNA 表达增强,但不能使SR哮喘HSP90 mRNA表达增强。 结论 SR哮喘中HSP90 mRNA表达相对不足造成HSP90/GR比值降低可能是SR哮喘形成的原因之一, IL-2+IL-4对GR和HSP90 mRNA表达的不同调节作用可能是形成SR哮喘HSP90/GR比值降低的原因之一。