Canary in the coliform mine: Exploring the industrial application limits of a microbial respiration alarm system.

Fundamental ecological principles of ecosystem-level respiration are extensively applied in greenhouse gas and elemental cycle studies. A laboratory system termed CEMS (Carbon Dioxide Evolution Measurement System), developed to explore microbial biofilm growth and metabolic responses, was evaluated as an early-warning system for microbial disturbances in industrial settings: in (a) potable water system contamination, and (b) bioreactor inhibition. Respiration was detected as CO2 production, rather than O2 consumption, including aerobic and anaerobic metabolism. Design, thresholds, and benefits of the remote CO2 monitoring technology were described. Headspace CO2 correlated with contamination levels, as well as chemical (R2 > 0.83-0.96) and microbiological water quality indicators (R2 > 0.78-0.88). Detection thresholds were limiting factors in monitoring drinking water to national and international standards (0 CFU/100 mL fecal coliforms) in both open- (>1500 CFU/mL) and closed-loop CO2 measuring regimes (>100 CFU/100 mL). However, closed-loop detection thresholds allow for the detection of significant contamination events, and monitoring less stringent systems such as irrigation water (<100 CFU/mL). Whole-system respiration was effectively harnessed as an early-warning system in bioreactor performance monitoring. Models were used to deconvolute biological CO2 fluctuations from chemical CO2 dynamics, to optimize this real-time, sustainable, low-waste technology, facilitating timeous responses to biological disturbances in bioreactors.

Ameliorative effect of sesamin in cisplatin-induced nephrotoxicity in rats by suppressing inflammation, oxidative/nitrosative stress, and cellular damage.

Nephrotoxicity of cisplatin (CP) involves renal oxidative stress and inflammation, and sesamin (a major liganin in many plants) has strong antioxidant and antiinflammatory actions. Therefore, we investigated here the possible mitigative action of sesamin on CP nephrotoxicity in rats. Sesamin was given orally (5 mg/kg/day, 10 days), and on the 7th day, some of the treated rats were injected intraperitoneally with either saline or CP (5 mg/kg). On the 11th day, rats were sacrificed, and blood and urine samples and kidneys were collected for biochemical estimation of several traditional and novel indices of renal damage in plasma and urine, several oxidative and nitrosative indices in kidneys, and assessment of histopathological renal damage. CP significantly and adversely altered all the physiological, biochemical and histopathological indices of renal function measured. Kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with sesamin. Sesamin treatment did not significantly alter the renal CP concentration. The results suggested that sesamin had ameliorated CP nephrotoxicity in rats by reversing the CP-induced oxidative stress and inflammation. Pending further pharmacological and toxicological studies sesamin may be considered a potentially useful nephroprotective agent.

Evidence supporting an independent association between childhood physical abuse and lifetime suicidal ideation.

A regionally representative Canadian sample was used to investigate the gender-specific relationship between childhood physical abuse and lifetime suicidal ideation. The prevalence of suicidal ideation was about five times higher in abused men and women compared with their nonabused counterparts. After controlling for five clusters of potentially confounding factors (adverse childhood conditions, socioeconomic factors, health behaviors, psychosocial stressors/chronic illnesses, and mental health), childhood physical abuse was significantly associated with suicidal ideation (OR(adjusted) women = 4.48, 95% CI = 3.32-6.04; men = 3.57, 95% CI = 2.08-6.14). These findings suggest childhood physical abuse is independently associated with suicidal ideation and highlight the importance of providing preventative treatment to childhood abuse survivors.

P2X7 receptor gene polymorphism analysis in rheumatoid arthritis.

The P2X7 receptor, a member of the P2X family of nucleotide-gated channels, is predominantly expressed by monocytic cells. The activation of this receptor has been associated with downstream-signalling cascades, resulting in the release of a number of inflammatory mediators. There are more than 815 single nucleotide polymorphisms (SNPs) that have been described in the human P2X7R gene, but only few have been functionally characterized. The main aim of this study is to determine whether P2X7R gene polymorphisms confer susceptibility to rheumatoid arthritis (RA). A total of 125 patients with RA and 158 healthy volunteers were enrolled in this study. DNA fragment was PCR amplified and sequenced on the AB 3130 Genetic Analyzer. No significant difference in allele frequencies of 489 C→T, 1096 C→G and 1513 A→C polymorphisms, among sporadic cases of RA and healthy controls was found. However, the 1513A/C genotype was significantly associated with the presence of rheumatoid factor and anti-MCV autoantibody in RA patients. Interestingly, the genotype frequency of 1068 A/A was 0.19 in the RA group and 0.09 in control group (P = 0.025). Consequently, this polymorphism (AA) is two folds greater in the RA group compared to controls. Moreover, this polymorphism was significantly associated with mean concentration of C-reactive protein in RA patients. In contrast, 946G→A and 1729 T→A were not detected in both groups. As a result, these two polymorphisms are uncommon in Omani Arab population. Polymorphism at position 1068 and 1513 in the P2X7R gene might contribute to the pathogenesis of RA. Moreover, the loss-of-function SNP at position 1096 C→G or the gain-of-function SNP at position 489 C→T of the P2X7 gene does not appear to be a susceptibility gene locus for the development of RA. Further studies are required to confirm this finding.

Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.

Carcinoembryonic antigen family of adhesion molecules in the cotton top tamarin (Saguinus oedipus).

Humans and the cotton top tamarin, a model for colitis and colorectal cancer, share carcinoembryonic antigen (CEA) moieties. We quantified CEA in colonic washings and extracts in both, and CEA bands were confirmed by Western blot. We compared CEA-family expression in tissues and serum in the tamarin with that of the common marmoset, which develops colitis but not cancer. CEA levels are higher in tamarin washings compared with humans, and higher than in marmosets extracts (P<0.005). CEA molecular species appear to be specific, and human CEA-family member epitopes are also found in these primates. The higher CEA levels in the tamarin may reflect the overall higher cancer prevalence.

Gastrointestinal tract antigenic profile of cotton-top tamarin, Saguinus oedipus, is similar to that of humans with inflammatory bowel disease.

As an animal model for human inflammatory bowel disease and colorectal cancer, the cotton-top tamarin remains controversial. Demonstration of antigenic similarity to the human would enhance its validity. Using colonic extracts and washings, we compared binding of seven monoclonal antibodies reactive with bowel and cancer antigens in both tamarins and humans with inflammatory bowel disease. Additionally, telomerase activity was tested for. Expression of a mucin antigen specific to human cancer was increased in tamarin colonic washings as well as aminoproteoglycans and EGFR in tamarin extracts, as compared to those of humans with inflammatory bowel disease (P < 0.005). An adenoma-associated antigen and k-ras p21 protein were negative in the tamarin. A trend to greater telomerase activity exists in tamarins. The antigenic similarity validates this model for human inflammatory bowel disease and colorectal cancer. A trend to increased telomerase activity in tamarins is consistent with the greater predisposition to cancer in these animals.

Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines.

Although accumulating evidence suggests a chemopreventive role for folic acid in colon cancer, the regulation of this process in unknown. We hypothesize that supplemental folic acid exerts its chemopreventive role by inhibiting mucosal hyperproliferation, an event considered to be central to the initiation of carcinogenesis in the gastrointestinal tract. The present investigation examines the effect of supplemental folic acid on proliferation of Caco-2 and HCT-116 colon cancer cell lines. Furthermore, because certain tyrosine kinases, particularly epidermal growth factor receptor (EGFR), play a role in regulating cell proliferation, we also examined the folic acid-induced changes in tyrosine kinase activity and expression of EGFR. In Caco-2 and HCT-116 cells, maintained in RPMI 1640 medium containing 1 microg/ml folic acid, we observed that the supplemental folic acid inhibited proliferation in a dose-dependent manner. Pretreatment of HCT-116 and Caco-2 cell lines with supplemental folic acid (1.25 microg/ml) completely abrogated transforming growth factor-alpha (TGF-alpha)-induced proliferation in both cell lines. Tyrosine kinase activity and the relative concentration of EGFR were markedly diminished in both cell lines following a 24-h exposure to supplemental folic acid. The folic acid-induced inhibition of EGFR tyrosine kinase activity in colon cancer cell lines was also associated with a concomitant reduction in the relative concentration of the 14-kDa membrane-bound precursor form of TGF-alpha. In conclusion, our data suggest that supplemental folic acid is effective in reducing proliferation in two unrelated colon cancer cell lines and that EGFR tyrosine kinase appears to be involved in regulating this process.

STK11/LKB1 germline mutations are not identified in most Peutz-Jeghers syndrome patients.

Germline mutations of the STK11 gene mapped to chromosome 19p13.3 are responsible for Peutz Jeghers syndrome (PJS), a dominant disorder associated with characteristic gastrointestinal hamartomatous polyps and a predisposition to various cancers. We conducted a detailed investigation of germline STK11 alterations by protein truncation test and genomic DNA sequence analysis in ten unrelated PJS families. We identified a novel truncating deletion spanning STK11 exons 2-7 in a single patient and several known polymorphisms. Loss of heterozygosity studies in PJS polyps of four of these patients identified an allelic deletion of D19S886 in another patient. Our results suggest that STK11 mutations account for only a proportion of PJS cases.

Monoclonal antibody Adnab-9 defines a preneoplastic marker in epithelium at risk for adenocarcinoma of the small intestine.

Unlike colorectal cancer, risk markers for adenocarcinoma of the small intestine (ASI) have not been identified. Because the demographic and pathological features of both of these diseases are similar, immunohistochemistry was performed using monoclonal antibodies for three colonic premalignant markers, Adnab-9 (recognizes a colonic adenoma epitope), CaCo3/61, and FBB2/29 (small intestine proteoglycans expressed ectopically in colonic neoplasms), in normal and neoplastic small intestinal epithelium, and the results were compared with normal controls. Adnab-9 was also examined in 20 familial adenomatous polyposis (FAP) patients, a population known to be at an increased risk for ASI. Immunohistochemistry in normal and neoplastic tissue (adenoma, adenocarcinoma) from 18 patients with primary adenocarcinoma of the small intestine was compared with normal small intestine from 10 nonneoplastic controls. Four of 10 (40%) cases of normal small intestinal epithelium from controls were mildly positive in less than 10% of crypts, versus strong staining (>50% of crypts) in 16 of 18 (89%) patients with adenocarcinoma, and in 17 of 20 (85%) patients with FAP (P<.05). Adnab-9 predominantly stained Paneth cells as well as rare crypt and basal villous goblet cells. Adenomatous epithelium from the adenocarcinoma cases and adenomas from the FAP patients showed staining of Adnab-9 in 63% and 78% of cases, respectively. Only 17% of adenocarcinomas were positive for Adnab-9. In contrast, neither CaCo3/61 nor FBB2/29 showed any significant differences in the degree of staining in normal small intestinal epithelium in patients with adenocarcinoma compared with controls. Enhanced Adnab-9 staining in normal small intestinal epithelium from patients who harbor adenocarcinoma, and in FAP patients, supports its role as a risk marker of small intestinal neoplasia.

Polyps as biomarkers for colorectal neoplasia.

Current understanding of colorectal carcinogenesis suggests a series of genetic changes occurring pari passu with morphological changes ultimately resulting in a cancerous lesion. The adenomatous polyp was originally the prototype of the preneoplastic lesion but recently, other colonic polyps, primarily the hamartomas, have been clinically characterized as colorectal cancer biomarkers with genetic changes found mainly in the mesenchymal component as opposed to the ectodermal, or epithelial element. This, with the current interest in angiogenesis playing a role in the propagation of neoplastic lesions, has now encompassed every tissue element and opened the way for an understanding of the oncogenic process. This has suggested that considerable interaction occurs between all tissue elements, including what was previously described as epithelial-matrix interactions. While hyperplastic polyps are thought not to confer risk for cancer, they may offer clues as to the first steps of the overall process. Microadenomas have introduced new clinical as well as biological considerations, as unique risk factors. Investigation of these lesions has moved from purely morphological correlations to mechanistic dissections of important biological pathways using both genetic and protein chemistry tools. This review explores the microcosm of the colonic polyp and its relation to cancer as the quintessential premalignant biomarker.

Shared tumor antigens in colorectal carcinoma and neuroendocrine tumors.

ND4 monoclonal antibody recognizes a tumor marker found on poorly differentiated colorectal cancer. We demonstrate its expression in 25% of gastrointestinal neuroendocrine tumors, which also express CEA in 37% of cases. As in colorectal cancer the ND4 marker is predominantly membrane bound in a colonic neuroendocrine tumor cell line, LCC-18 (p < 0.05). The ND4 marker is absent in a poorly differentiated colorectal cancer cell line that does not express CEA or other tumor antigens. Shed antigen in the serum of patients with neuroendocrine tumors is detected in only five of seven patients with the carcinoid syndrome and two of four of those without evidence of the syndrome. However, the reactivity was less in the patients with localized disease, and this test is unlikely to be of diagnostic utility in this group of patients. The sharing of this antigen in colorectal cancer and neuroendocrine tumors is not universal, but does support the common-cell progenitor theory for the origin of these tumors.

Zollinger-Ellison syndrome, acromegaly, and colorectal neoplasia.

Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in which colorectal neoplasia has been described, but the incidence in the former condition may not be increased. We describe four patients with colorectal neoplasia associated with the ZES and review other published cases. Tissue ELISA with Adnab-9 antibody, a putative colorectal cancer risk marker, from a patient with ZES and from seven patients with acromegaly was compared to 13 controls at average risk for colorectal neoplasia. The patient with ZES without detectable colonic neoplasia and seven patients with acromegaly had increased binding of Adnab-9 in the colonic mucosa by ELISA. The difference was significant for the acromegaly patients compared to the controls (p < 0.05). The accumulated 34 instances of colorectal neoplasia in ZES patients suggests that this association may not be rare. Adnab-9 expression, detectable in both ZES and acromegaly, may reflect predisposition to colorectal neoplasia in both hyper-secretory states. Therefore, while a basis for association of colorectal neoplasia and hypergastrinemia exists, the clinical data are not compelling enough to warrant surveillance of patients with ZES. To resolve this problem, more definitive case control studies should be conducted.

Cellular signals regulating antibiotic sensitivities of bacteria.

The effects of bacterial masses upon the drug resistance of neighboring bacteria were investigated. The experiments were performed with plastic Petri dishes divided into two identical compartments. A growing mass of Bacillus subtilis (signal emitter cell) in one compartment exerted enhancing effects upon the erythromycin and streptomycin resistance of Bacillus carboniphilus (signal recipient) cells, sparsely seeded in the other compartment, through the plastic wall and the air. These effects of the growing mass of cells are attributed to the emission of "sonic" signals.