A review of 10 children on continuous ambulatory peritoneal dialysis

The experience of continuous ambulatory peritoneal dialysis in children of the Queen Mary Hospital for the past 11 years was reviewed. Seven boys and three girls (aged 4.3 to 15.9 years) were treated for a mean of 27 months (range 5 to 58 months). There was significant biochemical improvement and patients led an active life on continuous ambulatory peritoneal dialysis. The commonest complications were peritonitis, occurring on average once per 10 patient-months and mostly due to Staphylococcus spp. The median catheter survival time was 30 months. There were two technique failures due to fungal peritonitis which necessitated transfer to haemodialysis due to fungal peritonitis. The only mortality was due to concurrent cardiac disease. This review supports that children with renal failure in Hong Kong can be maintained on long term dialysis with a reasonable quality of life. However, significant morbidity due to infective and mechanical complications still exists. Continuous ambulatory peitonitis dialysis remains a temporary treatment modality while patients are waiting for renal transplantation.published_or_final_versio

Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma

Growing evidence has revealed high expression levels of stanniocalcin-1 (STC1) in different types of human cancers. Numerous experimental studies using cancer cell lines demonstrated the involvement of STC1 in inflammatory and apoptotic processes; however the role of STC1 in carcinogenesis remains elusive. Hepatocellular carcinoma (HCC) an exemplified model of inflammation-related cancer, represents a paradigm of studying the association between STC1 and tumor development. Therefore, we conducted a statistical analysis on the expression levels of STC1 using clinicopathological data from 216 HCC patients. We found that STC1 was upregulated in the tumor tissues and its expression levels was positively correlated with the levels of interleukin (IL)-6 and IL-8. Intriguingly tumors with greater expression levels of STC1 (tumor/normal >= 2) were significantly smaller than the lower level (tumor/normal<2) samples (p = 0.008). A pharmacological approach was implemented to reveal the functional correlation between STC1 and the ILs in the HCC cell-lines. IL-6 and IL-8 treatment of Hep3B cells induced STC1 expression. Lentiviral-based STC1 over-expression in Hep3B and MHCC-97L cells however showed inhibitory action on the pro-migratory effects of IL-6 and IL-8 and reduced size of tumor spheroids. The inhibitory effect of STC1 on tumor growth was confirmed in vivo using the stable STC1-overexpressing 97L cells on a mouse xenograft model. Genetic analysis of the xenografts derived from the STC1-overexpressing 97L cells, showed upregulation of the pro-apoptotic genes interleukin-12 and NOD-like receptor family, pyrin domain-containing 3. Collectively, the anti-inflammatory and pro-apoptotic functions of STC1 were suggested to relate its inhibitory effect on the growth of HCC cells. This study supports the notion that STC1 may be a potential therapeutic target for inflammatory tumors in HCC patients.published_or_final_versio

Higher incidence of falls in winter among older people in Hong Kong

Purpose: This study aims at determining whether there is a seasonal pattern of falls among older people in Hong Kong and exploring the possible mechanisms underlying the seasonal pattern. Methods: The falls data were obtained from a 1-year prospective study conducted in 200-2007 which includes all the older people aged 60 years or more with a fall presenting to Accident and Emergency Department of a regional hospital in Hong Kong. The occurrence of falls among the 12 months was recorded and was used to correlate with weather data, including air temperature, relative humidity, and rainfall, in each month during the study period. Analyses were also carried out to examine if there was any signification association between occurrence of falls in four seasons and various factors, including age, gender and living arrangement of the fallers, location of falls, and predisposing factors for their falls. Results: There was a peak in occurrence of falls among the older people during winter. A significant correlation was found between a higher number of falls and lower air temperature and lower relative humidity. Age, gender, and location of falls for the fallers were not associated with the peak seasons (winter and autumn) and nonpeak seasons (spring and summer). Significantly larger proportion of falls occurred among people living in old age home during the peak season compared with the nonpeak season. Higher proportion of fallers during the peak season had lower limbs weakness as compared with that in nonpeak season. Multivariate logistic regression showed that only living arrangement and risky behavior were significantly associated with fall occurrence in peak season. Conclusion: A higher incidence of falls in winter among older people in Hong Kong was observed and possible mechanisms contributing to this seasonal pattern were explored. Further studies on intervention to minimize its impact on risk of falling among older people are indicated. Copyright © 2011, Asia Pacific League of Clinical Gerontology & Geriatrics. Published by Elsevier Taiwan LLC. All rights reserved.link_to_subscribed_fulltex

IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-kB activation

Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and is associated with poor prognosis due to the high incidences of metastasis and tumor recurrence. Our previous study showed that overexpression of p21-activated protein kinase 1 (PAK1) is frequently observed in HCC and is associated with a more aggressive tumor behavior, suggesting that PAK1 is a potential therapeutic target in HCC. In the current study, an allosteric small molecule PAK1 inhibitor, IPA-3, was evaluated for the potential in suppressing hepatocarcinogenesis. Consistent with other reports, inhibition of PAK1 activity was observed in several human HCC cell lines treated with various dosages of IPA-3. Using cell proliferation, colony formation and BrdU incorporation assays, we demonstrated that IPA-3 treatment significantly inhibited the growth of HCC cells. The mechanisms through which IPA-3 treatment suppresses HCC cell growth are enhancement of apoptosis and blockage of activation of NF-κB. Furthermore, our data suggested that IPA-3 not only inhibits the HCC cell growth, but also suppresses the metastatic potential of HCC cells. Nude mouse xenograft assay demonstrated that IPA-3 treatment significantly reduced the tumor growth rate and decreased tumor volume, indicating that IPA-3 can suppress the in vivo tumor growth of HCC cells. Taken together, our demonstration of the potential preclinical efficacy of IPA-3 in HCC provides the rationale for cancer therapy.published_or_final_versio

Hormonal regulation of endometrial olfactomedin expression and its suppressive effect on spheroid attachment onto endometrial epithelial cells

Background Olfactomedin (Olfm) is a member of a diverse group of extracellular matrix proteins important for neuronal growth. Recent microarray studies identified Olfm as one of the down-regulated transcripts in receptive endometrium at the time of embryo attachment and implantation. However, the underlying molecular mechanisms that govern Olfm expression and its effect on embryo attachment and implantation remain unknown. Methods The expression of Olfm in the human endometrium was investigated by real-time PCR, western blotting and immunohistochemistry on human endometrial biopsies from natural and ovarian stimulated cycles. To investigate the function of Olfm in trophoblastendometrial cell attachment, an in vitro spheroid-endometrial cell co-culture study was performed. Results Human endometrial Olfactomedin-1 and -2(Olfm-1 and -2) transcripts decreased significantly from the proliferative to the secretory phases of the menstrual cycle. Olfm protein was strongly expressed in the luminal and glandular epithelium and moderately in the stromal cells of human endometria. Ovarian stimulation significantly decreased (P < 0.05) the expression of endometrial Olfm-1 and -2 transcripts in patients receiving IVF treatment when compared with those in the natural cycle. Importantly, recombinant Olfm-1 suppressed JAr spheroid attachment onto Ishikawa cells and this was not associated with changes of β-catenin and E-cadherin expression in trophoblast and endometrial cells. Conclusions Decreased expression of Olfm during the receptive phase of the endometrium may allow successful trophoblast attachment for implantation. © 2010 The Author.postprin

Sex hormones and apoptosis and immunoglobulin production in systemic lupus erythematosus

BACKGROUND: SLE is an autoimmune disease that affects predominantly female of reproductive age. Previous studies have suggested an immunomodulatory role of sex hormones in the pathogenesis of SLE. Objectives: To examine the effects of various sex hormones on apoptosis and immunoglobulin production by peripheral blood mononuclear cells (PBMCs) in SLE patients …published_or_final_versio

Excessive ovarian stimulation up-regulates the Wnt-signaling molecule DKK1 in human endometrium and may affect implantation: An in vitro co-culture study

Background: High serum estradiol (E2) levels following ovarian stimulation lead to reduced implantation and pregnancy rates, yet the underlying mechanisms remain unknown. We investigated if aberrant expression of genes in the Wnt-signaling pathway may be involved. Methods: Microarray and real-time PCR analysis were performed to analyze gene expression profiles of endometrial samples taken at day hCG + 7 in stimulated cycles, and days LH + 7 and LH + 10 in natural cycles. Expression of several Wnt-signaling transcripts, including Dickkopf homolog 1 (DKK1), DKK2 and secreted frizzled-related protein 4 (sFRP4), was analyzed throughout the menstrual cycle. JAr spheroid/Ishikawa endometrial cell co-culture experiments were established to study effects of DKK1 on spheroid attachment in vitro. Results: We identified 351 differentially expressed genes. Endometrial samples taken at hCG + 7 had similar expression profiles to those at LH + 10. DKK1 transcripts were up-regulated and DKK2 and sFRP4 were down-regulated in the stimulated compared with LH + 7 group (all P < 0.05). DKK1 transcripts were low in proliferative phase (PS) and increased in late-secretory phase (LS, P < 0.05), although DKK2 peaked in mid-secretory phase (P < 0.05). sFRP4 transcripts were high in PS. Treatment of spheroid with recombinant human DKK-1 protein dose-dependently suppressed (P < 0.05 versus control) spheroids attachment onto endometrial cells (associated with decreased-catenin protein): this suppression was nullified by anti-DKK1 antibody.CONCLUSIONGene expression patterns in stimulated cycles resembled those of LS in natural cycles, when the implantation window is about to close, suggesting high serum E2 and/or progesterone concentrations may advance endometrial development, altering the implantation window and possibly decreasing pregnancy rate. Aberrant expression of DKK1 might impair embryo attachment and implantation in vivo.postprin

Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3

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Lineage Divergence and Historical Gene Flow in the Chinese Horseshoe Bat (Rhinolophus sinicus)

PMCID: PMC3581519This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV

Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells