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1.  Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice 
British Journal of Cancer  2010;103(8):1182-1191.
Background:
Dietary (n-6)-polyunsaturated fatty acids influence cancer development, but the mechanisms have not been well characterised in gastric carcinoma.
Methods:
We used two in vivo models to investigate the effects of these common dietary components on tumour metastasis. In a model of experimental metastasis, immunocompromised mice were fed diets containing linoleic acid (LA) at 2% (LLA), 8% (HLA) or 12% (VHLA) by weight and inoculated intraperitoneally (i.p.) with human gastric carcinoma cells (OCUM-2MD3). To model spontaneous metastasis, OCUM-2MD3 tumours were grafted onto the stomach walls of mice fed with the different diets. In in vitro assays, we investigated invasion and ERK phosphorylation of OCUM-2MD3 cells in the presence or absence of LA. Finally, we tested whether a cyclooxygenase (COX) inhibitor, indomethacin, could block peritoneal metastasis in vivo.
Results:
Both the HLA and VHLA groups showed increased incidence of tumour nodules (LA: 53% HLA: 89% VHLA: 100% P<0.03); the VHLA group also displayed increased numbers of tumour nodules and higher total volume relative to LLA group in experimental metastasis model. Both liver invasion (78%) and metastasis to the peritoneal cavity (67%) were more frequent in VHLA group compared with the LLA group (22% and 11%, respectively; P<0.03) in spontaneous metastasis model. We also found that the invasive ability of these cells is greatly enhanced when exposed to LA in vitro. Linoleic acid also increased invasion of other scirrhous gastric carcinoma cells, OCUM-12, NUGC3 and MKN-45. Linoleic acid effect on OCUM-2MD3 cells seems to be dependent on phosphorylation of ERK. The data suggest that invasion and phosphorylation of ERK were dependent on COX. Indomethacin decreased the number of tumours and total tumour volume in both LLA and VHLA groups. Finally, COX-1, which is known to be an important enzyme in the generation of bioactive metabolites from dietary fatty acids, appears to be responsible for the increased metastatic behaviour of OCUM-2MD3 cells in the mouse model.
Conclusion:
Dietary LA stimulates invasion and peritoneal metastasis of gastric carcinoma cells through COX-catalysed metabolism and activation of ERK, steps that compose pathway potentially amenable to therapeutic intervention.
doi:10.1038/sj.bjc.6605881
PMCID: PMC2967057  PMID: 20842125
gastric carcinoma; dietary fatty acid; cyclooxygenase; metastasis; invasion
3.  Isotopic evidences for microbiologically mediated and direct C input to soil compounds from three different leaf litters during their decomposition 
We show the potentiality of coupling together different compound-specific isotopic analyses in a laboratory experiment, where 13C-depleted leaf litter was incubated on a 13C-enriched soil. The aim of our study was to identify the soil compounds where the C derived from three different litter species is retained. Three 13C-depleted leaf litter (Liquidambar styraciflua L., Cercis canadensis L. and Pinus taeda L., δ13CvsPDB ≈ −43‰), differing in their degradability, were incubated on a C4 soil (δ13CvsPDB ≈ −18‰) under laboratory-controlled conditions for 8 months. At harvest, compound-specific isotope analyses were performed on different classes of soil compounds [i.e. phospholipids fatty acids (PLFAs), n-alkanes and soil pyrolysis products]. Linoleic acid (PLFA 18:2ω6,9) was found to be very depleted in 13C (δ13CvsPDB ≈ from −38 to −42‰) compared to all other PLFAs (δ13CvsPDB ≈ from −14 to −35‰). Because of this, fungi were identified as the first among microbes to use the litter as source of C. Among n-alkanes, long-chain (C27–C31) n-alkanes were the only to have a depleted δ13C. This is an indication that not all of the C derived from litter in the soil was transformed by microbes. The depletion in 13C was also found in different classes of pyrolysis products, suggesting that the litter-derived C is incorporated in less or more chemically stable compounds, even only after 8 months decomposition.
doi:10.1007/s10311-008-0141-6
PMCID: PMC2837225  PMID: 20234880
δ13C; Litter decomposition; n-Alkanes; PLFA; Pyrolysis-GC/MS-C-IRMS; SOM
4.  Low human immunodeficiency virus type 1 (HIV-1) DNA burden as a major cause for failure to detect HIV-1 DNA in clinical specimens by PCR. 
Journal of Clinical Microbiology  1995;33(1):205-208.
To determine the sensitivity of a nested PCR procedure for detecting human immunodeficiency virus type 1 DNA in clinical specimens, 553 peripheral blood mononuclear cell samples obtained from 268 human immunodeficiency virus type 1-seropositive subjects were assayed by use of two independent primer sets for each sample. Overall, 1,088 of 1,106 (98.37%) reactions were positive. Investigation of the negative reactions showed that a low viral burden in some infected subjects, rather than primer-template mismatches, was the primary cause for the false-negative PCR results.
PMCID: PMC227909  PMID: 7699043
5.  Detection of subclinical autonomic neuropathy in constipated patients using a sweat test. 
Gut  1992;33(11):1539-1543.
Chronic idiopathic constipation may be the result of an autonomic neuropathy. This hypothesis was tested in 23 constipated patients and 17 age matched controls, using the acetylcholine sweat spot test devised to test autonomic integrity in diabetes. Acetylcholine (0.01%) was injected in the dorsum of the foot painted with a mixture of starch and iodine. Active sweat glands appeared on the surface of the skin as small black dots which were photographed and counted, using a grid with 60 subareas. Two measurements were made: the number of dots per unit subarea (sweat spot test score) and the % number of abnormal subareas (with less than six spots). These two parameters were correlated. The median sweat spot test score was 9.53 in patients and 13.92 in controls (p = 0.0001), the receiver operating characteristic curve showing that a score of 12 delimited normal and abnormal subjects. Increasing age was correlated with a low score in patients, probably because of prolonged symptoms. Seventy per cent of patients and one control had a borderline or abnormal number of subareas. These results suggest that idiopathic constipation is associated with a degree of autonomic denervation. The sweat spot test is an easy, inexpensive method to test this hypothesis and deserves a place in the clinical assessment of slow transit constipated patients.
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PMCID: PMC1379542  PMID: 1452080
6.  Effects of vaccines on the canine immune system. 
The effects of several commercially available polyvalent canine vaccines on the immune system of the dog were examined. The results demonstrated that the polyvalent vaccines used in this study significantly suppressed the absolute lymphocyte count and that most of the polyvalent vaccines significantly suppressed lymphocyte response to mitogen, but had no effect on natural effector cell activity, neutrophil chemiluminescence, nor antibody response to canine distemper virus. The individual vaccine components from the polyvalent vaccines when inoculated alone did not significantly suppress the lymphocyte response to mitogen. However, when canine distemper virus was combined with canine adenovirus type 1 or canine adenovirus type 2, significant suppression in lymphocyte responsiveness to mitogen occurred. The results indicate that interactions between canine distemper virus and canine adenovirus type 1 or canine adenovirus type 2 are responsible for the polyvalent vaccine induced suppression of lymphocyte responsiveness.
PMCID: PMC1255540  PMID: 2540897
7.  Operative risk of correction of atrioventricular septal defects. 
British Heart Journal  1984;52(3):258-265.
Between 1 January 1975 and 31 December 1982, 111 patients with atrioventricular septal defect underwent surgical repair. Of these, 43 had the complete, 11 the intermediate, and 57 the partial form. The postoperative mortality rate was 37%, 9%, and 6% respectively. To determine which factors were independently responsible for the operative risk multivariate analysis of the surgical mortality was applied simultaneously to all three forms of the malformation. The form of defect, although strongly influencing the natural history and clinical presentation, was not by itself an operative risk factor. The risk was related primarily to failure to obtain a well functioning atrioventricular valve, to the presence of left ventricular dominance, to the degree of pulmonary vascular resistance, and, finally, to the technique of reconstructing a two leaflet left atrioventricular valve. The small size of the patient was also a significant incremental risk factor, but if the other factors were not unfavorable good results could be achieved in small infants with mortality rates less than 10%. Multivariate analysis showed that severe postoperative left atrioventricular valve malfunction was related to the technique used to reconstruct a "normal" two leaflet left atrioventricular valve. These findings support the policy of reconstructing the left atrioventricular valve as a three leaflet valve. Nevertheless, the implicit beneficial effect of this technique has not as yet proved to be statistically significant.
PMCID: PMC481622  PMID: 6466511
8.  The Connective Tissue Septa in the Foetal Human Lung * 
Thorax  1959;14(1):3-13.
Images
PMCID: PMC1018466  PMID: 13635639

Results 1-8 (8)