Genome sequences of eight prophages isolated from Lactococcus lactis dairy strains

P335 group phages represent the most divergent phage group infecting dairy Lactococcus lactis strains and have significant implications for the dairy processing industry. Here, we report the complete genome sequences of eight lactococcal prophages chemically induced from industrial lactococcal strains that propagate lytically on one of two laboratory strain

Terrace Standard, February, 09, 2000

Background. Loss of vessel wall integrity by degradation is essential for the development of abdominal aortic aneurysm (AAA) and ultimately its rupture. The observed greater rupture rate in women with AAA might be related to gender differences in the biomechanical properties of the aneurysm wall. The aim of the study was to compare the biomechanically important structure of collagen between men and women with AAA. Methods. Biopsies of the aneurysm walls were obtained during elective open repair of men (n = 14) and women (n = 14) treated for AAA. High-performance liquid chromatography (HPLC), Western blot, messenger RNA expression, and histochemical analyses were performed to assess the cross-linking and the amount and the composition of collagen. Results. There was neither a difference in the thickness of the aneurysm wall, nor in the histological evaluation of the collagen composition between the sexes. Relative collagen content in the aneurysm wall was similar in men and women, as assessed by messenger RNA expression and HPLC. Collagen cross-linking differed between the sexes; women had more lysyl pyridinoline (LP) than men (0.140 vs 0.07; P = .005), resulting in a lower hydroxyl pyridinoline (HP):LP ratio (3.28 vs 8.41; P = .003). There was no difference in messenger RNA and protein expressions of lysyl hydroxylase and lysyl oxidase to associate with the lower HP:LP ratio in women. Conclusions. The composition of collagen in the aneurysm wall of men and women are in several aspects similar, with the exception of collagen cross-linking, suggesting that the difference in rupture rate between the sexes rather depend on the composition of other vessel wall structures. Clinical Relevance The marked differences in prevalence and rupture risk of abdominal aortic aneurysm between men and women suggest gender to be of importance for both aneurysm development and progression. To study the amount and composition of collagen in men and women is of great importance for the understanding of the degenerative process occurring in aneurysms in both sexes and how it potentially differs, in regards to the increased rupture rate observed in women

Detecting Lactococcus lactis prophages by Mitomycin C-mediated induction coupled to flow cytometry analysis

Most analyzed Lactococcus lactis strains are predicted to harbor one or more prophage genomes within their chromosome; however, the true extent of the inducibility and functionality of such prophages cannot easily be deduced from sequence analysis alone. Chemical treatment of lysogenic strains with Mitomycin C is known to cause induction of temperate phages, though it is not always easy to clearly identify a lysogenic strain or to measure the number of released phage particles. Here, we report the application of flow cytometry as a reliable tool for the detection and enumeration of released lactococcal prophages using the green dye SYTO-9

Genetic and functional characterisation of the lactococcal P335 phage-host interactions

Background: Despite continuous research efforts, bacterio(phages) infecting Lactococcus lactis starter strains persist as a major threat to dairy fermentations. The lactococcal P335 phages, which are currently classified into four sub-groups (I-IV), are the second most frequently isolated phage group in an industrial dairy context. Results: The current work describes the isolation and comparative genomic analysis of 17 novel P335 group phages. Detailed analysis of the genomic region of P335 phages encoding the so-called “baseplate”, which includes the receptor binding protein (RBP) was combined with a functional characterization of the RBP of sub-group III and IV phages. Additionally, calcium-dependence assays revealed a specific requirement for calcium by sub-group IV phages while host range analysis highlighted a higher number of strains with CWPS type A (11 of 39 strains) are infected by the P335 phages assessed in this study than those with a C (five strains), B (three of 39 strains) or unknown (one of 39 strains) CWPS type. Conclusions: These analyses revealed significant divergence among RBP sequences, apparently reflecting their unique interactions with the host and particularly for strains with a type A CWPS. The implications of the genomic architecture of lactococcal P335 phages on serving as a general model for Siphoviridae phages are discussed

Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma.

Proteinases are involved in tumour invasion and metastasis. Several matrix metalloproteinases (MMPs) have been shown to be increased in various human carcinomas. We assessed the levels of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in 50 gastric carcinomas and corresponding mucosa using quantitative gelatin zymography. Both MMP levels were significantly enhanced in gastric carcinomas compared with adjacent mucosal tissue, showed a relatively poor intercorrelation and no relation was found with histopathological carcinoma classifications according to Laurén, WHO and tumour-node-metastasis (TNM). Cox's multivariate proportional hazards analyses revealed that high carcinomatous MMP values are of prognostic significance for a poor overall survival of the patients, independent of the major clinicopathological parameters

Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer

In a pioneer study, we showed 10 years ago that enhanced tissue levels of the matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in gastric cancers, as determined by zymography, were related with worse overall survival of the patients. To corroborate these observations, we now assessed MMP-2 and MMP-9 with new techniques in an expanded group of gastric cancer patients (n=81) and included for comparison MMP-7, MMP-8 and the tissue inhibitors of MMPs, TIMP-1 and -2. All MMPs and TIMP-1 were significantly increased in tumour tissue compared to normal gastric mucosa. Matrix metalloproteinase-7, -8 and -9, and the TIMPs showed some correlations with the clinicopathologic parameters TNM, WHO and Laurén classification, but their levels were not related with survival. Regardless of the determination method used, that is, enzyme-linked immunosorbent assay or bioactivity assay, an enhanced tumour MMP-2 level did not show a significant correlation with any of the clinicopathological parameters, but was confirmed to be an independent prognostic factor in gastric cancer

Comparison of Carboplatin With 5-Fluorouracil vs. Cisplatin as Concomitant Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Background: Chemoradiotherapy (CRT) including three cycles of cisplatin is considered the standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, around one-third of the patients cannot complete cisplatin because of toxicity. Carboplatin plus 5-fluorouracil (carbo-5FU) is another accepted treatment option with a different toxicity profile. We compared tolerability and efficacy of concomitant carbo-5FU and cisplatin. Patients and Methods: We conducted a retrospective analysis of LA-HNSCC patients treated with CRT in two Dutch cancer centers between 2007 and 2016. All patients received intensity-modulated radiotherapy. One center routinely administered carboplatin 300–350 mg/m2 at day 1, 22, and 43 followed by 5FU 600 mg/m2/day for 96 h. The other center used cisplatin 100 mg/m2 at day 1, 22, and 43. The primary endpoint of this study was chemotherapy completion rate. Secondary endpoints included overall survival (OS), disease-free survival (DFS), locoregional control (LRC) and distant metastasis–free interval (DMFS), toxicity, and unplanned admissions. Results: In the carbo-5FU cohort (n = 211), 60.2% of the patients completed chemotherapy vs. 76.7% (p < 0.001) of the patients in the cisplatin cohort (n = 223). Univariate analysis showed a higher risk of death in the carbo-5FU cohort [hazard ratio (HR) 1.53, 95% CI, 1.09–2.14, p = 0.01] with a 3-year OS of 65.4 vs. 76.5% for cisplatin. OS was independently associated with T and N stage and p16 status, but not with chemotherapy regimen (HR 1.08, 95% CI, 0.76–1.55, p = 0.65). Three-year DFS was 70.0% for carbo-5FU vs. 78.6% for cisplatin (HR 1.37, 95% CI, 0.93–2.01, p = 0.05). A similar outcome was observed for both LRC (HR 1.27, 95% CI, 0.74–2.09, p = 0.4) and DMFS (HR 1.08, 95% CI 0.62–1.90, p = 0.77). The risk of discontinuation for chemotherapy-associated toxicity was higher in the carbo-5FU cohort than in the cisplatin cohort (relative risk = 1.69). Conclusion: LA-HNSCC patients treated with concomitant carbo-5FU completed chemotherapy less frequently than patients treated with cisplatin. Treatment regimen was not an independent prognostic factor for OS