Frequent somatic loss of BRCA1 in breast tumours from BRCA2 germ-line mutation carriers and vice versa

Breast cancer susceptibility genes BRCA1 and BRCA2 are tumour suppressor genes the alleles of which have to be inactivated before tumour development occurs. Hereditary breast cancers linked to germ-line mutations of BRCA1 and BRCA2 genes almost invariably show allelic imbalance (AI) at the respective loci. BRCA1 and BRCA2 are believed to take part in a common pathway in maintenance of genomic integrity in cells. We carried out AI and fluorescence in situ hybridization (FISH) analyses of BRCA2 in breast tumours from germ-line BRCA1 mutation carriers and vice versa. For comparison, 14 sporadic breast tumours were also studied. 8 of the 11 (73%) informative BRCA1 mutation tumours showed AI at the BRCA2 locus. 53% of these tumours showed a copy number loss of the BRCA2 gene by FISH. 5 of the 6 (83%) informative BRCA2 mutation tumours showed AI at the BRCA1 locus. Half of the tumours (4/8) showed a physical deletion of the BRCA1 gene by FISH. Combined allelic loss of both BRCA1 and BRCA2 gene was seen in 12 of the 17 (71%) informative hereditary tumours, whereas copy number losses of both BRCA genes was seen in only 4/14 (29%) sporadic control tumours studied by FISH. In conclusion, the high prevalence of AI at BRCA1 in BRCA2 mutation tumours and vice versa suggests that somatic events occurring at the other breast cancer susceptibility gene locus may be selected in the cancer development. The mechanism resulting in AI at these loci seems more complex than a physical deletion.   http://www.bjcancer.com © 2001 Cancer Research Campaig

Lake Ontario Long Term Biological Monitoring Program: 1981, 1982 Data Base

The Bioindex, or Long Term Biological Monitoring Program, was developed to: 1) determine normal seasonal patterns and annual ranges of abundance, community structure, and when possible, productivity of the biological components - phytoplankton, zooplankton, and benthos; 2) relate the biological components to variations in the physical, nutrient, and biological environment; and, 3) assess the adopted sampling strategy for long term monitoring. The data bases from the first two years are summarized in this document

Risk profiles and prognosis of treated and untreated hypertensive men and women in a population-based longitudinal study: the Reykjavik Study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe aim was to examine the risk profiles and prognosis of treated and untreated hypertensive subjects and examine to what degree confounding by indication was present in a population-based cohort study with up to 30-year follow-up. The study population consisted of 9328 men and 10 062 women, aged 33-87 years at the time of attendance from 1967 to 1996. The main outcome measures were myocardial infarction (MI), cardiovascular disease (CVD) mortality and all-cause mortality. Comparing the risk profiles between treated and untreated subjects entering the study showed significantly higher values for some risk factors for treated subjects. During the first 10 years, hypertensive men without treatment, compared with those treated, had a significantly lower risk of suffering MI, CVD and all-cause mortality, hazard ratio (HR) 0.72 (95% CI; 0.57, 0.90), 0.75 (95% CI; 0.59, 0.95) and 0.81 (95% CI; 0.61, 0.98), respectively. No significant differences in outcome were seen during the following 20 years. In identically defined groups of women, no significant differences in mortality were seen between groups. Subgroup analysis, at two stages of the study 5 years apart, revealed that some cardiovascular risk factors had a higher prevalence in hypertensive men who were treated at the later stage, compared with those who remained untreated (P=0.004). In conclusion, hypertensive treated men had a worse prognosis during the first 10 years of follow-up than untreated ones, which is most likely due to worse baseline risk profile. Hypertensive men that were treated at a later stage had a worse risk profile than those not treated at a later stage

Lake Erie 1993, Western, West Central and Eastern Basins: Change in Trophic Status, and Assessment of the Abundance, Biomass and Production of the Lower Trophic Levels

The western and west central basins were mesotrophic and the eastern basin was oligotrophic, based on many biological and chemical parameters measured in 1993. Gradients were observed for most parameters, with chlorophyll a, nitrogen, phosphorus, silica, and light extinction decreasing from west to east. In the western basin, phytoplankton biomass declined by 51% from 1983-85. Phytoplankton photosynthesis (g C·m-2), predicted from total phosphorus (TP) using a relationship developed in other offshore productivity studies in Lake Ontario, declined by 35% in 1993, without a corresponding decline in phosphorus (P) loading or TP. Diatoms decreased and there was a shift towards smaller phytoplankton species. These changes were attributed to zebra mussel filtration, but were not of sufficient magnitude to reduce zooplankton biomass. In the west central basin, the reductions in phytoplankton biomass were modest. Photosynthesis (g C·m-2) in 1993, was in line with that predicted by TP and the empirical relationship developed in other offshore studies. Limited mussel populations in the west central basin, resulting from low hypolimnetic oxygen concentrations, caused little change in the phytoplankton. There also were no reductions in mean biomass of zooplankton from 1984-87. In the eastern basin, phytoplankton biomass declined by 49% from 1983-85. Photosynthesis (g C·m-2) declined by 50% from the value predicted, from TP and the empirical relationship developed for other studies, for 1983-85, without a decline in P-leading. TP was lower in 1993 and was attributed to filtering by Dreissena and subsequent redirection of pelagic material to the sediments. Phytoplankton species indicative of eutrophy were reduced and there was an overall shift towards smaller species. Zooplankton biomass was also reduced. Mean zooplankton community size and the loss of Daphnia sp. suggest that predation by planktivores as well as a reduced food supply, affected zooplankton biomass in 1993. The Dreissena population also affected the benthic community structure as Diporeia were virtually eliminated from the eastern basin and Gammarus increased in all basins. Benthic biomass was 40% higher on average than in 1979. Dreissena dominated benthic production at all stations except offshore in the west-central basin

Pseudoacromegaly: A Differential Diagnostic Problem for Acromegaly With a Genetic Solution.

Acromegaly is usually not a difficult condition to diagnose once the possibility of this disease has been raised. However, a few conditions present with some aspects of acromegaly or gigantism but without growth hormone (GH) excess. Such cases are described as "pseudoacromegaly" or "acromegaloidism". Here we describe a female patient investigated for GH excess at 10 years of age for tall stature since infancy (height and weight > +3 standard deviations) and typical acromegalic features, including large hands/feet, large jaw, tongue, hoarse deep voice, and headache. Results of radiography of the sella turcica and GH response at an oral glucose tolerance test and insulin-arginine- thyrotrophin-luteinizing hormone-releasing hormone test were normal. Ethinylestradiol and medroxyprogesterone were given for 2 years; this successfully stopped further height increase. Although the patient's growth rate plateaued, coarsening of the facial features and acral enlargement also led to investigations for suspicion of acromegaly at 23 and 36 years of age, both with negative results. On referral at the age of 49 years, she had weight gain, sweating, sleep apnea, headaches, joint pain, and enlarged tongue. Endocrine assessment again showing normal GH axis was followed by genetic testing with a macrocephaly/overgrowth syndrome panel. A denovo mutation in the NSD1 gene (c.6605G>C; p.Cys2202Ser) was demonstrated. Mutations affecting the same cysteine residue have been identified in patients with Sotos syndrome. In summary, Sotos syndrome and other overgrowth syndromes can mimic the clinical manifestations of acromegaly or gigantism. Genetic assessment could be helpful in these cases

Assessment of Abundance, Biomass and Production of the Lower Trophic Levels in the Eastern Basin of Lake Erie, 1994

The Lake Erie Biomonitoring (LEB) program conducted in 1994, focused on the eastern basin of the lake, resampling the same sites as in 1993. Nutrient conditions were similar in the two years. Responses differed between the stratified offshore and unstratified nearshore. At the offshore station, seasonal phytoplankton biomass was 56% higher in 1994 than in 1993 and apparently resulted from a reduction in grazing pressure by Dreissena. Dreissena biomass and their potential clearance rates at the offshore station were much lower in the spring of 1994 than in the spring of 1993 (2.5 vs. 14.9 m3·m·2·d·\u27), respectively. Despite this increase in phytoplankton biomass, chlorophyll (Chi) and phytoplankton photosynthesis (PP) were not significantly higher in 1994. Dinoflagellates, which have lower Chl:C and lower photosynthesis:Chl ratios than other groups of phytoplankton, accounted for much of the increase in biomass. Rotifer biomass decreased by 50% and zooplankton biomass by 40% between the two years. Calanoids were responsible for much of the decrease in zooplankton biomass. Composition also shifted towards larger bodied cladocerans, such as Daphnia and Bythotrephes, and away from Bosmina. This shift coincided with changes in predation pressure. Age-one smelt abundance was extremely high in 1993 and low in 1994, while the reverse was true of the YOY smelt. Age-one smelt consume mainly cladocerans and the YOY, copepods (REF). At the nearshore stations, seasonal PP and Chi were well below that expected given the total phosphorus (TP) concentration, indicating that Dreissena had an important impact on phytoplankton photosynthesis in this region. Low transparency due to suspended sediments also contributed to the low PP at station El. Zooplankton biomass was lower in 1994 than in 1993, and species composition and size shifted. Daphnia increased and calanoids and Bosmina decreased in the nearshore as in the offshore, presumably in response to changes in the smelt population. However, Bythotrephes decreased and rotifer biomass increased unlike in the offshore

Treatment as Prevention for Hepatitis C (TraP Hep C) - a nationwide elimination programme in Iceland using direct-acting antiviral agents

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesA nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct-acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long-term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016-2018. Emphasis is placed on early case finding and treatment of patients at high risk for transmitting HCV, that is people who inject drugs (PWID), as well as patients with advanced liver disease. In addition to treatment scale-up, the project also entails intensification of harm reduction efforts, improved access to diagnostic tests, as well as educational campaigns to curtail spread, facilitate early detection and improve linkage to care. With these efforts, Iceland is anticipated to achieve the WHO hepatitis C elimination goals well before 2030. This article describes the background and organization of this project. Clinical trial number: NCT02647879.Merck Astellas Gilead Gilead Sciences AbbVie BM