Ocular complications of paediatric patients with nephrotic syndrome

Purpose : To investigate ocular complications arising from nephrotic syndrome and/or its treatments in children. Methods : A cross‐sectional study was conducted in a teaching hospital. A total of 31 paediatric patients with nephrotic syndrome were studied. Comprehensive ophthalmic assessments on best‐corrected visual acuity, intraocular pressure, slit‐lamp and fundus examination were taken. Information regarding histological diagnosis of nephrotic syndrome and its treatment regimen in each patient was reviewed and analysed. Results : Bilateral posterior subcapsular cataracts were detected in three of 29 patients (10.3%) who received steroid therapy. Two had normal vision while one had visual acuity reduced to 6/15 in both eyes. The age of onset of the nephrotic syndrome in these three patients was 2 years, which was significantly younger than those without cataract (5.4 ± 3.2 years, P < 0.001). Three patients (9.7%) had isolated asymptomatic fundal findings of tortuous and dilated retinal vessels. Hypertensive retinopathy was found in one patient (3.2%). No steroid‐induced glaucoma, uveitis, ocular infection, or other eye complications related to the use of steroids or other immunosuppressive agents were noted. Conclusions : Children who have nephrotic syndrome often require prolonged, intermittent high dose of systemic corticosteroid therapy. Paediatricians should be aware of the potential risk of developing steroid‐related complications, especially posterior subcapsular cataract. It appears to have a higher risk when steroid therapy is used in very young patients. Early detection would help to prevent amblyopia development, particularly in the group of immature eyes.     

蓣知子皂甙IV的结构

从木通科木通属植物白木通[Akebia trifoliata(Thunb.)Koidz.var.australis(Diels)Rehd]种子的乙醇提取物中以硅胶层析等方法得四种三萜皂甙。其中甙IV是新天然产物,命名为蓣知子皂甙IV(yuzhiziosideIV)。根据化学和光谱分析,确定甙IV的结构为3-O-β-D-吡喃木糖基-(1→2)-a-L-吡喃阿拉伯糖齐墩果酸-28-O-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖酯甙。另外皂甙B(I)、皂甙C(II)和皂甙D(III)为已知物。这些化合物在白木通种子中均是首次得到。     

Amplification of genes encoding human myeloid membrane antigens after DNA-mediated gene transfer

Spontaneous amplification of genes encoding two different human myeloid surface antigens was observed after DNA-mediated gene transfer of cellular DNA from the human myeloid cell line HL-60 into NIH-3T3 mouse fibroblasts. Transformed recipient cells with highly amplified expression of either of two donor membrane polypeptides, gp150 or p67, were isolated with a fluorescence-activated cell sorter (FACS), using monoclonal antibodies specific for human myeloid cells. Immunoprecipitation of enzymatically radioiodinated polypeptides from the surface of transformed NIH-3T3 cells confirmed that expression of these proteins was amplified tenfold to 20-fold in comparison to their expression on human myeloid cell lines. The cellular DNA of cloned secondary and tertiary transformants expressing high levels of gp150 and p67 contained amplified sets of DNA restriction fragments that hybridized with human repetitive DNA sequences. Cytogenetic analysis of subclones overexpressing gp150 revealed extrachromosomal double minutes (DMs), whose presence correlated with the unstable expression of the membrane polypeptide. Human sequences in gp150-positive clones did not localize to chromosomes, consistent with their association with extrachromosomal DMs. By contrast, p67-positive subclones stably expressed the antigen, and in situ hybridization to metaphase spreads demonstrated that amplified human DNA sequences were integrated into a specific marker chromosome. Cytogenetic analysis of the parental NIH- 3T3 subclone used in these studies disclosed DMs in a low percentage of metaphases, suggesting that the recipient cells have a propensity for amplifying donor DNA.     

Interleukin-3, GM-CSF, and TPA induce distinct phosphorylation events in an interleukin 3-dependent multipotential cell line

The mechanism of action of the hemopoietic growth factor, murine interleukin-3 (mIL-3), was investigated using an mIL-3-dependent multipotential hematopoietic cell line, B6SUtA1. Murine granulocyte- macrophage colony-stimulating factor (mGM-CSF) was as potent as mIL-3 in stimulating these cells. In addition, sodium orthovanadate, an inhibitor of phosphotyrosine phosphatase, and 12-O-tetradecanoyl- phorbol-13-acetate (TPA), a known activator of protein kinase C, also stimulated DNA synthesis in these cells, suggesting that protein phosphorylation might be involved in the mechanism of action of mIL-3 and mGM-CSF. To assess this possibility, intact B6SUtA1 cells exposed for brief periods to mIL-3, mGM-CSF, and TPA were analyzed for changes in phosphorylation patterns using metabolic 32P-labeling and antibodies to phosphotyrosine. Both mIL-3 and mGM-CSF induced the serine-specific phosphorylation of a 68-Kd cytosolic protein, whereas all three agents stimulated the serine-specific phosphorylation of a 68-Kd membrane protein. Furthermore, mIL-3 stimulated tyrosine phosphorylation of the 68-Kd membrane protein, as well as of 140-, 90-, 55, and 40-Kd proteins. The 90-Kd protein was also tyrosine phosphorylated in response to mGM-CSF. These phosphotyrosine containing proteins were not detected in TPA-treated cells. These results indicate that protein phosphorylations on tyrosine and serine residues occur in B6SUtA1 cells following short-term incubation with mIL-3 or mGM-CSF and that most of these phosphorylation events are mediated by kinases other than protein kinase C (PkC).     

Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation

The hypothesis that extracellular truncation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony- stimulating factor, and IL-5 (h beta c) can lead to ligand-independent activation was tested by infecting factor-dependent hematopoietic cell lines with retroviruses encoding truncated forms of h beta c. A truncation, resembling that in v-Mpl, and retaining 45 h beta c-derived extracellular residues, led to constitutive activation in the murine myeloid cell line, FDC-P1. However, infection of cells with retrovirus encoding a more severely truncated receptor, retaining only 7 h beta c- derived extracellular residues, did not confer factor independence on these cells. These experiments show that truncation activates the receptor and define a 37-amino acid segment of h beta c (H395-A431) which contains two motifs conserved throughout the cytokine receptor superfamily (consensus Y/H XX R/Q VR and WSXWS), as essential for factor-independent signaling. The mechanism of activation was also investigated in less severe truncations. A receptor that retains the entire membrane-proximal domain (domain 4) also conferred factor independent growth on FDC-P1 cells; however, a retrovirus encoding a truncated form of h beta c having two intact membrane proximal domains did not have this ability, suggesting that domain 3 may have an inhibitory role in h beta c. The ability of these receptors to confer factor independence was cell specific as demonstrated by their inability to confer factor-independent growth when introduced into the murine IL-3-dependent pro-B cell line BaF-B03. These results are consistent with a model in which activation requires unmasking of an interactive receptor surface in domain 4 and association with a myeloid- specific receptor or accessory component. We suggest that in the absence of ligand intramolecular interactions prevent inappropriate signaling.     

Mandatory Procedures and Fairness in Mental Impairment Hearings

Uncertainty has attended procedures for adjudging unfitness to stand trial in Victoria pursuant to the Crimes (Mental Impairment and Unfitness to be Tried) Act 1997 (Vic) and how “special hearings” should be conducted when a person is determined to be unfit to stand trial but does not wish to pursue the defence of not guilty because of mental impairment. In R v Langley [2008] VSCA 81, (2009) 19 VR 90 the Victorian Court of Appeal clarified the procedures to be employed at jury trials on such matters and quashed a decision not in conformity with proper procedures, making clear that denial of fairness to such accused persons has the potential to result in appealable error.