Microsatellite instability and novel mismatch repair gene mutations in northern Chinese population with Hereditary non‐polyposis colorectal cancer

OBJECTIVE: Hereditary non‐polyposis colorectal cancer (HNPCC) syndrome is the most common cause of hereditary colorectal cancer with an early age of onset. Microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found in the majority of HNPCC families and provide an opportunity for genetic diagnosis and prophylactic screening. The MMR gene mutation spectrum may vary across different populations and be influenced by founder mutations that prevail in specific ethnic groups. China is a big and ancient nation with enormous genetic diversity, which is especially notable between the northern and southern Chinese populations. A MMR gene mutation database for the southern Chinese population based in Hong Kong has been previously established. This study compares the MMR gene mutation spectrum and the MSI of HNPCC between the northern and southern Chinese populations. METHODS: Twenty‐five HNPCC families from northern China were systematically analyzed. The MSI analysis was performed using five loci in the USA National Cancer Institute (NCI) panel (D2S123, D5S346, BAT‐25, BAT‐26 and BAT‐40) by PCR from the tumor and normal tissue. MSH2, MSH6 and MLH1 were performed using immunohistochemical staining. Two founder mutations of MSH2 and MLH1 were examined by PCR base analyses using primers flanking the two deletion sites (c.1452_1455delAATG in MSH2 and 1.8 kb deletion involving exon 11 of MLH1) . RESULTS: Of the 25 families collected, 19 met Bethesda guideline (BG) 1 and six met BG3. Twenty‐two (15.7%) were extra‐colonic cancers with gastric cancer (in seven patients) being the most common cancer type. Of the 25 tumors analyzed, 21 (84%) were high level microsatellite instability (MSI‐H) and four (16%) were microsatellite stable (MSS). Eighteen (86%) of the 21 MSI‐H tumors showed loss of either the MLH1 or the MSH2 protein. Three MSI‐H tumors and all four MSS tumors showed no loss of expression of the three MMR proteins. Out of the 21 patients with MSI‐H tumors, 12 (57%) showed pathogenic germline mutations in either MLH1 (n = 8) or MSH2 (n = 4). Overall, three novel mutations (in patients H22, H17 and H29) have been identified. One of them, c.503_4insA, caused a frameshift mutation in the MLH1 gene. The other two were found in the MSH2 gene, including a frameshift (c.899_890insAT) and a splice junction (IVS7‐1G→A, SA of Exon 8) mutation. CONCLUSIONS: The results suggest a distinctly different mutation spectrum of MMR genes between northern and southern Chinese populations and call for a systematic, nationwide study to facilitate the design of a MMR gene mutation detection strategy tailored for individual populations in China.     

Elevated levels of transforming growth factor-beta(1) in serum of patients with stable bronchiectasis

Bronchiectasis is a chronic inflammatory and infective airway disease characterized by irreversible dilatation of the bronchi and persistent purulent sputum. Transforming growth factor-beta(1) (TGF-beta(1)) has been found to be increased in the lungs or bronchoalveolar lavage fluid of patients with inflammatory lung diseases. However, little is known on the serum TGF-beta(1) levels in patients with bronchiectasis. We aimed to determine the serum TGF-beta(1) concentrations in 95 patients with stable bronchiectasis (63 women; mean+/-sd age, 58.9+/-14.1 years) and 68 control subjects (23 women; 48.9+/-12.8 years) by ELISA, and to correlate with clinical parameters. The serum TGF-beta(1) levels were significantly higher in bronchiectatic patients compared with control subjects (median [range], 1812.5 pg/ml [1226.4-4114.5 pg/ml] vs. 1342.4 pg/ml [940.3-2371.7 pg/ml]; P<0.001). There was, however, no correlation between serum TGF-beta(1) levels with FEV(1) (% predicted), FVC (% predicted), 24h sputum volume, the number of bronchiectatic lung lobes or total white blood cell count (P>0.05). Our findings support previous indications that TGF-beta(1) may contribute to bronchiectatic airway inflammation. Further studies on the potential mechanisms and pathogenesis implications of this elevation should also be pursued in future.     

Immunomodulatory Activities of HERBSnSENSES™ Cordyceps — in Vitro and in Vivo Studies

The commercially available HERBSnSENSES? Cordyceps (HSCS) belongs to a cultivated strain of Cordyceps sinensis whose immunomodulatory activities has been renowned in traditional Chinese medicine (TCM) for centuries. The present report is the first that describes its immunomodulatory features through a series of in vitro and in vivo experiments. We measured, in peripheral blood mononuclear cells the in vitro effects of HSCS on the gene expression of cytokines and cytokine receptors, cytokine release, and surface expression of cytokine receptors using cDNA expression array, cytometric bead array (CBA), and immunoflorescence staining, respectively, as well as macrophage phagocytosis and monocyte production of H₂O₂ using flow cytometry. Sixty female BALB/c mice were fed with either HSCS (40 mg/kg/day) or water consecutively for 14 days. Proliferation, cytokine liberation, and CD3/4/8 expression of splenic cells were measured using 5-bromo-2′-deoxyuridine proliferation ELISA, CBA, and cytometry immunoflorescence staining, respectively. In vitro results demonstrated that HSCS induced the production of interleukin(IL)-1β, IL-6, IL-10 and tumor necrosis factor alphaα from PBMC, augmented surface expression of CD25 on lymphocytes, and elevated macrophage phagocytosis and monocyte production of H₂O₂. In vivo results showed that HSCS did not induce splenomegaly and cytokine overliberation. Our results possibly provide the biochemical basis for future clinical trials.     

A Three‐wave Study of Antecedents of Work–Family Enrichment: The Roles of Social Resources and Affect

On the basis of conservation of resources theory (Hobfoll, 1989 ) and the resource‐gain‐development perspective (Wayne, Grzywacz, Carlson, & Kacmar, 2007 ), this paper examines the differential impact of specific social resources (supervisory support and family support) on specific types of affect (job satisfaction and family satisfaction, respectively), which, in turn, influence work‐to‐family enrichment and family‐to‐work enrichment, respectively. A sample of 276 Chinese workers completed questionnaires in a three‐wave survey. The model was tested with structural equation modelling. Job satisfaction at time 2 partially mediated the relationship between time 1 supervisory support and time 3 work‐to‐family enrichment (capital), and the effect of supervisory support on work‐to‐family enrichment (affect) was fully mediated by job satisfaction. Family satisfaction at time 2 fully mediated the relationship between time 1 family support and time 3 family‐to‐work enrichment (affect, efficiency). Implications for theory, practice and future research are discussed. Copyright © 2013 John Wiley & Sons, Ltd.     

Systematic review of pathophysiological changes following hepatic resection

Objectives

Major hepatic resection is now performed frequently and with relative safety, but is accompanied by significant pathophysiological changes. The aim of this review is to describe these changes along with interventions that may help reduce the risk for adverse outcomes after major hepatic resection.

Methods

The MEDLINE, EMBASE and CENTRAL databases were searched for relevant literature published from January 2000 to December 2011. Broad subject headings were ‘hepatectomy/’, ‘liver function/’, ‘liver failure/’ and ‘physiology/’.

Results

Predictable changes in blood biochemistry and coagulation occur following major hepatic resection and alterations from the expected path indicate a complicated course. Susceptibility to sepsis, functional renal impairment, and altered energy metabolism are important sequelae of post-resection liver failure.

Conclusions

The pathophysiology of post-resection liver failure is difficult to reverse and thus strategies aimed at prevention are key to reducing morbidity and mortality after liver surgery.