Ukupni i specifični mortalitet u radnika izloženih azbestu od 1907. do 1985. godine

Total and cause-specific mortality data for the 1907 -1985 period were compared between cohorts of male asbestos-cement workers (N = 1908) and referents (N = 726), using Poisson regression modelling. The rate ratio (RR) for total mortality was significantly increased (1.3) among the exposed workers, as was mortality from non-malignant respiratory disease (RR= 2.2). Numerically, but not statistically significantly, raised ratios were found for respiratory (RR= 1.6) and gastrointestinal (RR= 1.3) cancers. The trend in the rate ratio for total mortality with time was better fitted with a curved line, than with a monotonic one, because of a period of increased risk up to the 1950s, and another one starting after 1970.Ukupni i specifični mortalitet za razdoblje od 1907. do 1985. godine uspoređen je u kohortama muških radnika koji su bili izloženi azbestu (N = 1908) s kontrolama (N = 726) pomoću Poissonove regresijske analize. Koeficijent regresije (RR) za ukupni mortalitet, kao i mortalitet od nemalignih respiratornih bolesti bio je statistički značajno viši i iznosio je 1,3, odnosno 2,2. Povećanje ovog koeficijenta nađeno je i za plućni (1,6) i gastrointestinalni karcinom (1,3), ali vrijednosti nisu statistički značajne

Mineralna vlakna, fibroza i azbestna tjelešca u plućnom tkivu radnika koji su bili izloženi azbestnom cementu

Samples of lung tissue taken from deceased asbestos-cement workers, with (N = 7) and without (N = 69) mesothelioma, and from individually matched controls (N = 96) were examined. The number of asbestos bodies and the grade of fibrosis were determined with light microscopy, and the type, size, and number of fibres with transmission electron microscopy and energy dispersive X-ray spectrometry. The asbestos content was, as expected, higher among the exposed workers than among the controls. Chrysotile was the major fibre type in terms of fibre count. Conversion to fibre mass reversed the pattern to a predominance of amphibole fibres, and accentuated the differences between exposed workers and controls. Duration of exposure and the number of asbestos bodies displayed significant associations with all the singular amphiboles (amosite, crocidolite, tremolite, and anthophyllite), but not with chrysotile. Fibrosis was related to the tremolite content, but not to chrysotile, both among exposed workers and controls. The workers with mesothelioma had higher levels of crocidolite and tremolite than the other asbestos-cement workers.Ispitivani su uzorci plućnog tkiva umrlih radnika koji su bili izloženi azbestnom cementu, s mezoteliomom, i bez njega, i njihovim odgovarajućim kontrolama. Broj azbestnih tjelešaca i stupanj fibroze određeni su svjetlosnim mikroskopom, a tip, veličina i broj vlakana elektronskom mikroskopijom i rendgenskom spektrometrijom. Sadržaj azbesta bio je veći kod izloženih radnika negoli u kontrola. Krizotilna vlakna bila su najbrojnija među formiranim vlaknima. Nađena je da je duljina izloženosti i broj azbestnih tjelešaca u korelaciji sa svim pojedinačnim amfolitima (amozit, krocidolit, tremolit i antofilit), ali ne i s krizotilom. Nalaz fibroze bio je u korelaciji s tremolitom, za razliku od krizolita, i to u eksponiranih i kontrolnih radnika. Uzorci plućnog tkiva radnika s mezoteliomom sadržavali su više krocidolita i tremolita od drugih radnika koji su bili izloženi azbestnom cementu

Challenging the heterogeneity of disease presentation in malignant melanoma-impact on patient treatment

There is an increasing global interest to support research areas that can assist in understanding disease and improving patient care. The National Cancer Institute (NIH) has identified precision medicine-based approaches as key research strategies to expedite advances in cancer research. The Cancer Moonshot program ( https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative ) is the largest cancer program of all time, and has been launched to accelerate cancer research that aims to increase the availability of therapies to more patients and, ultimately, to eradicate cancer. Mass spectrometry-based proteomics has been extensively used to study the molecular mechanisms of cancer, to define molecular subtypes of tumors, to map cancer-associated protein interaction networks and post-translational modifications, and to aid in the development of new therapeutics and new diagnostic and prognostic tests. To establish the basis for our melanoma studies, we have established the Southern Sweden Malignant Melanoma Biobank. Tissues collected over many years have been accurately characterized with respect to the tumor and patient information. The extreme variability displayed in the protein profiles and the detection of missense mutations has confirmed the complexity and heterogeneity of the disease. It is envisaged that the combined analysis of clinical, histological, and proteomic data will provide patients with a more personalized medical treatment. With respect to disease presentation, targeted treatment and medical mass spectrometry analysis and imaging, this overview report will outline and summarize the current achievements and status within malignant melanoma. We present data generated by our cancer research center in Lund, Sweden, where we have built extensive capabilities in biobanking, proteogenomics, and patient treatments over an extensive time period

Plasma proteomic profiling in postural orthostatic tachycardia syndrome (POTS) reveals new disease pathways

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder characterized by excessive heart rate increase on standing, leading to debilitating symptoms with limited therapeutic possibilities. Proteomics is a large-scale study of proteins that enables a systematic unbiased view on disease and health, allowing stratification of patients based on their protein background. The aim of the present study was to determine plasma protein biomarkers of POTS and to reveal proteomic pathways differentially regulated in POTS. We performed an age- and sex-matched, case–control study in 130 individuals (case–control ratio 1:1) including POTS and healthy controls. Mean age in POTS was 30 ± 9.8 years (84.6% women) versus controls 31 ± 9.8 years (80.0% women). We analyzed plasma proteins using data-independent acquisition (DIA) mass spectrometry. Pathway analysis of significantly differently expressed proteins was executed using a cutoff log2 fold change set to 1.2 and false discovery rate (p-value) of < 0.05. A total of 393 differential plasma proteins were identified. Label-free quantification of DIA-data identified 30 differentially expressed proteins in POTS compared with healthy controls. Pathway analysis identified the strongest network interactions particularly for proteins involved in thrombogenicity and enhanced platelet activity, but also inflammation, cardiac contractility and hypertrophy, and increased adrenergic activity. Our observations generated by the first use a label-free unbiased quantification reveal the proteomic footprint of POTS in terms of a hypercoagulable state, proinflammatory state, enhanced cardiac contractility and hypertrophy, skeletal muscle expression, and adrenergic activity. These findings support the hypothesis that POTS may be an autoimmune, inflammatory and hyperadrenergic disorder

Selected reactive oxygen species and antioxidant enzymes in common bean after Pseudomonas syringae pv. phaseolicola and Botrytis cinerea infection

Phaseolus vulgaris cv. Korona plants were inoculated with the bacteria Pseudomonas syringae pv. phaseolicola (Psp), necrotrophic fungus Botrytis cinerea (Bc) or with both pathogens sequentially. The aim of the experiment was to determine how plants cope with multiple infection with pathogens having different attack strategy. Possible suppression of the non-specific infection with the necrotrophic fungus Bc by earlier Psp inoculation was examined. Concentration of reactive oxygen species (ROS), such as superoxide anion (O2 -) and H2O2 and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were determined 6, 12, 24 and 48 h after inoculation. The measurements were done for ROS cytosolic fraction and enzymatic cytosolic or apoplastic fraction. Infection with Psp caused significant increase in ROS levels since the beginning of experiment. Activity of the apoplastic enzymes also increased remarkably at the beginning of experiment in contrast to the cytosolic ones. Cytosolic SOD and guaiacol peroxidase (GPOD) activities achieved the maximum values 48 h after treatment. Additional forms of the examined enzymes after specific Psp infection were identified; however, they were not present after single Bc inoculation. Subsequent Bc infection resulted only in changes of H2O2 and SOD that occurred to be especially important during plant–pathogen interaction. Cultivar Korona of common bean is considered to be resistant to Psp and mobilises its system upon infection with these bacteria. We put forward a hypothesis that the extent of defence reaction was so great that subsequent infection did not trigger significant additional response

Skeletal concentrations of lead, cadmium, zinc, and silver in ancient North American Pecos Indians.

Bone samples of 14 prehistoric North American Pecos Indians from circa 1400 A.D. were analyzed for lead, cadmium, zinc, and silver by graphite furnace atomic absorption spectrometry to establish the baseline levels of these elements in an ancient North American population. Measurements of outer and inner bone fractions indicate the former were contaminated postmortem for lead, zinc, and cadmium. The contamination-adjusted average (mean +/- SD) level of lead (expressed as the ratio of atomic lead to atomic calcium) in bones of the Indians was 8.4 +/- 4.4 x 10(-7)), which was similar to ratios in bones of ancient Peruvians (0.9 to 7.7 x 10(-7)) and significantly lower than ratios in bones of modern adults in England and the United States (210 to 350 x 10(-7]. The adjusted average concentrations (microgram per gram dry weight) of biologic cadmium, silver, and zinc in the Pecos Indian bones were 0.032 +/- 0.013, 0.094 +/- 0.044, and 130 +/- 66, as compared to concentrations of 1.8, 0.01 to 0.44, and 75 to 170 in the bones of modern people, respectively. Therefore, cadmium concentrations in Pecos Indian bones are also approximately 50-fold lower than those of contemporary humans. These data support earlier findings that most previously reported natural concentrations of lead in human tissues are erroneously high and indicate that natural concentrations of cadmium are also between one and two orders of magnitude lower than contemporary concentrations

Correlation of histopathologic characteristics to protein expression and function in malignant melanoma

BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information. PATIENTS AND METHODS: Regional lymph node metastases obtained from ten patients with metastatic melanoma (stage III) were analyzed by histopathology and proteomics using mass spectrometry. Out of the ten patients, six had clinical follow-up data. The protein deep mining mass spectrometry data was related to the histopathology tumor tissue sections adjacent to the area used for deep-mining. Clinical follow-up data provided information on disease progression which could be linked to protein expression aiming to identify tissue-based specific protein markers for metastatic melanoma and prognostic factors for prediction of progression of stage III disease. RESULTS: In this feasibility study, several proteins were identified that positively correlated to tumor tissue content including IF6, ARF4, MUC18, UBC12, CSPG4, PCNA, PMEL and MAGD2. The study also identified MYC, HNF4A and TGFB1 as top upstream regulators correlating to tumor tissue content. Other proteins were inversely correlated to tumor tissue content, the most significant being; TENX, EHD2, ZA2G, AOC3, FETUA and THRB. A number of proteins were significantly related to clinical outcome, among these, HEXB, PKM and GPNMB stood out, as hallmarks of processes involved in progression from stage III to stage IV disease and poor survival. CONCLUSION: In this feasibility study, promising results show the feasibility of relating proteomics to histopathology and clinical outcome, and insight thus can be gained into the molecular processes driving the disease. The combined analysis of histological features including the sample cellular composition with protein expression of each metastasis enabled the identification of novel, differentially expressed proteins. Further studies are necessary to determine whether these putative biomarkers can be utilized in diagnostics and prognostic prediction of metastatic melanoma