Features of ovarian cancer in Lynch syndrome (Review).

Science.gov (United States)

Nakamura, Kanako; Banno, Kouji; Yanokura, Megumi; Iida, Miho; Adachi, Masataka; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Nomura, Hiroyuki; Hirasawa, Akira; Tominaga, Eiichiro; Aoki, Daisuke

2014-11-01

Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9-2.7%. Lynch syndrome accounts for 10-15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65-75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome.

Lynch syndrome-associated neoplasms

DEFF Research Database (Denmark)

Shia, Jinru; Holck, Susanne; Depetris, Giovanni

2013-01-01

It was a century ago that Warthin, a pathologist, first described the clinical condition now known as Lynch syndrome. One hundred years later, our understanding of this syndrome has advanced significantly. Much of the progress took place over the last 25 years and was marked by a series...... of interacting developments from the disciplines of clinical oncology, pathology, and molecular genetics, with each development serving to guide or enhance the next. The advancement of our understanding about the pathology of Lynch syndrome associated tumors exemplifies such intimate interplay among disciplines....... Today, accumulative knowledge has enabled surgical pathologists to detect tumors that are likely to be associated with Lynch syndrome, and the pathologist is playing an increasingly more important role in the care of these patients. The pathologist's ability is afforded primarily by information gained...

Diagnosing Lynch Syndrome

LENUS (Irish Health Repository)

Gleeson, J

2016-11-01

Lynch Syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is a hereditary condition that increases an individual’s risk of developing a constellation of cancers. These most commonly arise in the colon, but also involve other solid organs such as the endometrium and ovaries in women, the stomach, brain and the skin. Ireland’s small population offers an opportunity to identify all those with Lynch Syndrome (LS) in the country, which would represent a powerful preventive opportunity to meaningfully impact on the incidence of cancer in Ireland.

Three molecular pathways model colorectal carcinogenesis in Lynch syndrome.

Science.gov (United States)

Ahadova, Aysel; Gallon, Richard; Gebert, Johannes; Ballhausen, Alexej; Endris, Volker; Kirchner, Martina; Stenzinger, Albrecht; Burn, John; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

2018-07-01

Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR-deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR-deficient cells by chemoprevention or vaccines against MMR deficiency-induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome. © 2018 UICC.

Milestones of Lynch syndrome: 1895-2015.

Science.gov (United States)

Lynch, Henry T; Snyder, Carrie L; Shaw, Trudy G; Heinen, Christopher D; Hitchins, Megan P

2015-03-01

Lynch syndrome, which is now recognized as the most common hereditary colorectal cancer condition, is characterized by the predisposition to a spectrum of cancers, primarily colorectal cancer and endometrial cancer. We chronicle over a century of discoveries that revolutionized the diagnosis and clinical management of Lynch syndrome, beginning in 1895 with Warthin's observations of familial cancer clusters, through the clinical era led by Lynch and the genetic era heralded by the discovery of causative mutations in mismatch repair (MMR) genes, to ongoing challenges.

Modernization and Lynching in the New South

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Mattias Smångs

2016-09-01

Full Text Available This article evaluates an emerging body of historical scholarship that challenges prevailing views of the primacy of rural conditions in southern lynching by positing that it was symbiotically associated with the processes of modernization underway in the region in the decades around 1900. Statistical analyses of lynching data that differentiate among events according to communal participation, support, and ceremony in Georgia and Louisiana from 1882 to 1930 and local-level indices of modernization (urbanization, rural depopulation, industrialization, agricultural commercialization, and dissolution of traditional family roles yield results that both support and contradict such a modernization thesis of lynching. The findings imply that the consequences of the social transformation in the South coinciding with the lynching era were not uniform throughout the region with regard to racial conflict and violence and that broad arguments proposing an intrinsic connection between modernization and lynchings therefore are overstated.

Lynch Syndrome: A Primer for Urologists and Panel Recommendations.

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Mork, Maureen; Hubosky, Scott G; Rouprêt, Morgan; Margulis, Vitaly; Raman, Jay; Lotan, Yair; O'Brien, Timothy; You, Nancy; Shariat, Shahrokh F; Matin, Surena F

2015-07-01

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is a common genetic disease. The predisposition of patients with Lynch syndrome to urological cancer, particularly upper tract urothelial carcinoma, is underappreciated. Urologists may be involved in several aspects of care involving Lynch syndrome, including identifying undiagnosed patients, surveillance of those with established Lynch syndrome or screening family members, in addition to treating patients with Lynch syndrome in whom upper tract urothelial carcinoma develops. We sought to increase awareness in the urological community about Lynch syndrome and provide some guidance where little currently exists. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement we reviewed the available published literature and guidelines from 1998 to 2014 on Lynch syndrome and its association with upper tract urothelial carcinoma. Recommendations based on the literature and the consensus of expert opinion are provided. No randomized or prospective study has been done to evaluate Lynch syndrome in the setting of urological cancer. All data were based on retrospective studies. Lynch syndrome is an autosomal dominant genetic disease caused by germline mutations in 4 mismatch repair genes, leading to the accumulation of DNA errors in microsatellite regions. Upper tract urothelial carcinoma develops in up to 28% of patients with known Lynch syndrome. The diagnosis of Lynch syndrome is established by clinical criteria, tumor tissue testing and genetic evaluation. Urologists should suspect Lynch syndrome when a patient with upper tract urothelial carcinoma presents before age 60 years or meets the 3-2-1 rule. Screening patients with Lynch syndrome for upper tract urothelial carcinoma presents a particular challenge. While no ideal screening test exists, at a minimum routine urinalysis is recommended using the American Urological Association guideline of 3 or more red

Lynch Syndrome: Genomics Update and Imaging Review.

Science.gov (United States)

Cox, Veronica L; Saeed Bamashmos, Anas A; Foo, Wai Chin; Gupta, Shiva; Yedururi, Sireesha; Garg, Naveen; Kang, Hyunseon Christine

2018-01-01

Lynch syndrome is the most common hereditary cancer syndrome, the most common cause of heritable colorectal cancer, and the only known heritable cause of endometrial cancer. Other cancers associated with Lynch syndrome include cancers of the ovary, stomach, urothelial tract, and small bowel, and less frequently, cancers of the brain, biliary tract, pancreas, and prostate. The oncogenic tendency of Lynch syndrome stems from a set of genomic alterations of mismatch repair proteins. Defunct mismatch repair proteins cause unusually high instability of regions of the genome called microsatellites. Over time, the accumulation of mutations in microsatellites and elsewhere in the genome can affect the production of important cellular proteins, spurring tumorigenesis. Universal testing of colorectal tumors for microsatellite instability (MSI) is now recommended to (a) prevent cases of Lynch syndrome being missed owing to the use of clinical criteria alone, (b) reduce morbidity and mortality among the relatives of affected individuals, and (c) guide management decisions. Organ-specific cancer risks and associated screening paradigms vary according to the sex of the affected individual and the type of germline DNA alteration causing the MSI. Furthermore, Lynch syndrome-associated cancers have different pathologic, radiologic, and clinical features compared with their sporadic counterparts. Most notably, Lynch syndrome-associated tumors tend to be more indolent than non-Lynch syndrome-associated neoplasms and thus may respond differently to traditional chemotherapy regimens. The high MSI in cases of colorectal cancer reflects a difference in the biologic features of the tumor, possibly with a unique susceptibility to immunotherapy. © RSNA, 2018.

Upper urinary tract carcinoma in Lynch syndrome cases.

Science.gov (United States)

Crockett, David G; Wagner, David G; Holmäng, Sten; Johansson, Sonny L; Lynch, Henry T

2011-05-01

Patients with Lynch syndrome are much more likely to have generally rare upper urinary tract urothelial carcinoma but not bladder urothelial carcinoma. While the risk has been quantified, to our knowledge there is no description of how this population of patients with Lynch syndrome and upper urinary tract cancer differs from the general population with upper urinary tract cancer. We obtained retrospective data on a cohort of patients with Lynch syndrome from the Hereditary Cancer Center in Omaha, Nebraska and compared the data to those on a control general population from western Sweden. These data were supplemented by a new survey about exposure to known risk factors. Of the patients with Lynch syndrome 91% had mutations in MSH2 rather than in MSH1 and 79% showed upper tract urothelial carcinoma a mean of 15.85 years after prior Lynch syndrome-type cancer. Median age at diagnosis was 62 years vs 70 in the general population (p Lynch syndrome 51% had urothelial carcinoma in the ureter while it occurred in the renal pelvis in 65% of the general population (p = 0.0013). Similar numbers of high grade tumors were found in the Lynch syndrome and general populations (88% and 74%, respectively, p = 0.1108). Upper urinary tract tumors develop at a younger age and are more likely to be in the ureter with an almost equal gender ratio in patients with Lynch syndrome. It has high grade potential similar to that in the general population. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

HUBUNGAN ANOPHELES BARBIROSTRIS DENGAN MALARIA

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Krisna Iryani

2013-03-01

Full Text Available Malaria is a disease caused by intercellular obligate protozoa genus of Plasmodium which is a parasite carried by female Anopheles mosquito. One of them is Anopheles barbirostris. Research in several places already proved that Anopheles barbirostris acts as a vector of malaria. One case that occurred in Cineam district, Tasikmalaya regency showed that Anopheles barbirostris is suspected as vector of malaria. This is proven through a research on the relationship between Anopheles barbirostris with malaria. Data was taken from the larvae and adult mosquitoes captured around Cineam village, Tasikmalaya. The observation was done in the open field and laboratory. Data and identification by pictorial key for female Anopheles showed that the population of Anopheles barbirostris was always a dominant population compared to another Anopheles species. Because of the breeding ponds and the resting places were around the village, it is suspected that they mainly bit humans. The result of the observation in laboratory showed the life cycle of Anopheles barbirostris are around 20-27 days, and the longevity of 20 days. Morphological identification of Anopheles barbirostris by pictorial key for female Anopheles showed that there is no any significant difference. This research showed that Anopheles barbirostris was suspected as vector of malaria in Cineam village, Tasikmalaya.

Advances in the study of Lynch syndrome in China.

Science.gov (United States)

Lu, Jun-Yu; Sheng, Jian-Qiu

2015-06-14

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers due to inherited mutations in mismatch repair (MMR) genes. During the last decades, there have been great advances in research on Chinese Lynch syndrome. This review mainly focuses on the genetic basis, clinicopathologic features, diagnosis, intervention, chemoprevention, and surveillance of Lynch syndrome in China. In addition to frequently altered MMR genes, such as MLH1, MSH2, MSH6, and MLH3, other MMR-associated genes, such as those encoding human exonuclease 1, transforming growth factor β receptor 2, and alanine aminopeptidase, metastasis-associated protein 2, adenomatosis polyposis coli down-regulated 1, and hepatic and glial cell adhesion molecule have also been implicated in Chinese Lynch syndrome. Most Chinese researchers focused on the clinicopathologic features of Lynch syndrome, and it is noticeable that the most frequent extracolonic tumor in northeast China is lung cancer, which is different from other areas in China. The Chinese diagnostic criteria for Lynch syndrome have been established to identify gene mutation or methylation. With regard to chemoprevention, celecoxib may be effective to prevent polyps relapse in Lynch syndrome carriers. Additionally, a colonoscopy-based surveillance strategy for the prevention and early detection of neoplasms in Lynch-syndrome carriers has been proposed.

Molecular subtype classification of urothelial carcinoma in Lynch syndrome.

Science.gov (United States)

Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias; Jönsson, Mats; Sjödahl, Gottfrid; Nilbert, Mef; Liedberg, Fredrik

2018-05-23

Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as Urothelial-like tumors with only 20% being Genomically Unstable, Basal/SCC-like or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger data sets revealed that Lynch syndrome-associated UC share molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the Urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

The influence of the area of the Serra da Mesa Hydroelectric Plant, State of Goiás, on the frequency and diversity of anophelines (Diptera: Culicidae): a study on the effect of a reservoir.

Science.gov (United States)

Melandri, Vanessa; Alencar, Jerônimo; Guimarães, Anthony Érico

2015-01-01

Bioecological aspects of anophelines (Diptera: Culicidae) near areas under the direct influence of the hydroelectric plant reservoir of Serra da Mesa in Goiás, Brazil, were analyzed. Samples were collected at the surrounding dam area during the phases before and after reservoir impoundment. The influence of climatic and environmental factors on the occurrence of Anopheles darlingi, Anopheles albitarsis, Anopheles triannulatus, Anopheles oswaldoi and Anopheles evansae was assessed using Pearson's correlations with indicators for richness and diversity as well as the index of species abundance (ISA) and the standardized index of species abundance (SISA). The highest anopheline density occurred during the phase after filling the tank; however, no direct correlation with the climatic factors was observed during this stage. The reservoir formation determined the incidence of the anopheline species. An. darlingi was the predominant species (SISA = 1.00). The significant difference (p < 0.05) observed between the species incidence during the different reservoir phases demonstrates the environmental effect of the reservoir on anophelines.

Prevalence of Lynch syndrome and Lynch-like syndrome among patients with colorectal cancer in a Japanese hospital-based population.

Science.gov (United States)

Chika, Noriyasu; Eguchi, Hidetaka; Kumamoto, Kensuke; Suzuki, Okihide; Ishibashi, Keiichiro; Tachikawa, Tetsuhiko; Akagi, Kiwamu; Tamaru, Jun-Ichi; Okazaki, Yasushi; Ishida, Hideyuki

2017-02-09

We investigated the prevalence of Lynch syndrome and Lynch-like syndrome among Japanese colorectal cancer patients, as there have been no credible data from Japan. Immunohistochemical analyses for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) were carried out in surgically resected, formalin-fixed paraffin-embedded specimens obtained from 1,234 newly diagnosed colorectal cancer patients between March 2005 and April 2014. The presence/absence of the BRAF V600E mutation and hypermethylation of the MLH1 promoter was analyzed where necessary. Genetic testing was finally undertaken in patients suspected as having Lynch syndrome. By the universal screening approach with immunohistochemical analysis for mismatch repair proteins followed by analyses for the BRAF V600E mutation and MLH1 promoter methylation status, 11 (0.9%) of the 1,234 patients were identified as candidates for genetic testing. Out of the 11 patients, 9 (0.7%) were finally diagnosed as having Lynch syndrome; the responsible genes included MLH1 (n = 1), MSH2 (n = 4), EPCAM (n = 1) and MSH6 (n = 3). The remaining two patients (0.2%) were regarded as having Lynch-like syndrome, since biallelic somatic deletion of the relevant mismatch repair genes was detected in the absence of germline mismatch repair alterations. None of the cases was identified as having germline MLH1 epimutation. The prevalence of Lynch syndrome among all newly diagnosed cases of colorectal cancer in Japan is in the same range as that recently reported by studies in Western population. The prevalence of Lynch-like syndrome seems to be extremely low. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Novos encontros de anofelíneos em recipientes artificiais

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Oswaldo Paulo Forattini

1998-12-01

Full Text Available Assinalam-se novos encontros de anofelíneos em recipientes artificiais. Um deles diz respeito a formas imaturas de Anopheles bellator em criadouros experimentais e outro é concernente ao achado de An. albitarsis l.s., em recipiente abandonado. Tecem-se considerações sobre a pressão seletiva representada pela produção, cada vez maior, de objetos descartáveis.

Molecular subtype classification of urothelial carcinoma in Lynch syndrome

DEFF Research Database (Denmark)

Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias

2018-01-01

Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome......-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial...... carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed...

Diagnosis of Lynch Syndrome: Genetic Testing Identifies a Potentially Deadly Hereditary Disease

Science.gov (United States)

... of Lynch Syndrome Follow us A Diagnosis of Lynch Syndrome Genetic testing identifies a potentially deadly hereditary disease ... helped Jack learn what was wrong. Jack had Lynch Syndrome—an inherited disorder. Lynch Syndrome increases the risk ...

Taxonomy Icon Data: Anopheles stephensi [Taxonomy Icon

Lifescience Database Archive (English)

Full Text Available Anopheles stephensi Anopheles stephensi Arthropoda Anopheles_stephensi_L.png Anopheles_stephen...si_NL.png Anopheles_stephensi_S.png Anopheles_stephensi_NS.png http://biosciencedbc.jp/taxonomy_i...con/icon.cgi?i=Anopheles+stephensi&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Anopheles+stephensi&...t=NL http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Anopheles+stephensi&t=S htt...p://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Anopheles+stephensi&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=149 ...

Recent discoveries in the molecular genetics of Lynch syndrome.

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Boland, C Richard

2016-07-01

Lynch syndrome is the inherited predisposition to cancer caused by a germline mutation in a DNA mismatch repair gene. The consequent tumors have a characteristic microsatellite instability (MSI) phenotype. Genomic sequencing of Lynch syndrome-associated colorectal cancers (CRCs) has demonstrated that these tumors have a substantially greater number of mutations than non-MSI CRCs, and that the target mutations driving tumor behavior are also different from what occurs in sporadic tumors. There are multiple non-Lynch syndrome entities that can create clinical confusion with that disease, including the acquired methylation of MLH1, Lynch-like syndrome, and Familial CRC-Type X. Patients with Lynch syndrome-associated CRCs have a substantially better prognosis, and there is growing evidence that this is due to the generation of immunogenic frameshift peptides as a consequence of defective DNA mismatch repair, and an effective immune response to the tumor.

Lynch Syndrome: Female Genital Tract Cancer Diagnosis and Screening.

Science.gov (United States)

Mills, Anne M; Longacre, Teri A

2016-06-01

Lynch syndrome is responsible for approximately 5% of endometrial cancers and 1% of ovarian cancers. The molecular basis for Lynch syndrome is a heritable functional deficiency in the DNA mismatch repair system, typically due to a germline mutation. This review discusses the rationales and relative merits of current Lynch syndrome screening tests for endometrial and ovarian cancers and provides pathologists with an informed algorithmic approach to Lynch syndrome testing in gynecologic cancers. Pitfalls in test interpretation and strategies to resolve discordant test results are presented. The potential role for next-generation sequencing panels in future screening efforts is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Mismatch repair genes in Lynch syndrome: a review

Directory of Open Access Journals (Sweden)

Felipe Cavalcanti Carneiro da Silva

Full Text Available Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2; mutL homolog 1 (MLH1; mutS homolog 6 (MSH6; postmeiotic segregation increased 2 (PMS2; and postmeiotic segregation increased 1 (PMS1. It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3, also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors, approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50% and MSH2 (40%, while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

PMS2 involvement in patients suspected of Lynch syndrome.

Science.gov (United States)

Niessen, Renée C; Kleibeuker, Jan H; Westers, Helga; Jager, Paul O J; Rozeveld, Dennie; Bos, Krista K; Boersma-van Ek, Wytske; Hollema, Harry; Sijmons, Rolf H; Hofstra, Robert M W

2009-04-01

It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families. Recently, it was shown that germline mutations in another mismatch repair gene, PMS2, play a far more important role in Lynch syndrome than initially thought. To explore this further, we determined the prevalence of pathogenic germline PMS2 mutations in a series of Lynch syndrome-suspected patients. Ninety-seven patients who had early-onset microsatellite instable colorectal or endometrial cancer, or multiple Lynch syndrome-associated tumors and/or were from an Amsterdam Criteria II-positive family were selected for this study. These patients carried no pathogenic germline mutation in MLH1, MSH2, or MSH6. When available, tumors were investigated for immunohistochemical staining (IHC) for PMS2. PMS2 was screened in all patients by exon-by-exon sequencing. We identified four patients with a pathogenic PMS2 mutation (4%) among the 97 patients we selected. IHC of PMS2 was informative in one of the mutation carriers, and in this case, the tumor showed loss of PMS2 expression. In conclusion, our study confirms the finding of previous studies that PMS2 is more frequently involved in Lynch syndrome than originally expected.

Immunohistochemical Pitfalls: Common Mistakes in the Evaluation of Lynch Syndrome.

Science.gov (United States)

Markow, Michael; Chen, Wei; Frankel, Wendy L

2017-12-01

At least 15% of colorectal cancers diagnosed in the United States are deficient in mismatch repair mechanisms. Most of these are sporadic, but approximately 3% of colorectal cancers result from germline alterations in mismatch repair genes and represent Lynch syndrome. It is critical to identify patients with Lynch syndrome to institute appropriate screening and surveillance for patients and their families. Exclusion of Lynch syndrome in sporadic cases is equally important because it reduces anxiety for patients and prevents excessive spending on unnecessary surveillance. Immunohistochemistry is one of the most widely used screening tools for identifying patients with Lynch syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

[A Case of Ascending Colon Cancer with Lynch Syndrome Who Underwent XELOX Adjuvant Chemotherapy].

Science.gov (United States)

Takase, Koki; Murata, Kohei; Kagawa, Yoshinori; Nose, Yohei; Kawai, Kenji; Sakamoto, Takuya; Naito, Atsushi; Murakami, Kohei; Katsura, Yoshiteru; Omura, Yoshiaki; Takeno, Atsushi; Nakatsuka, Shinichi; Takeda, Yutaka; Kato, Takeshi; Tamura, Shigeyuki

2018-01-01

Lynch syndrome is an inherited syndrome with the development of the colorectal and various other cancers. Lynch syndrome is caused by mutations in the mismatch repair genes. A 33 year-old male underwent XELOX adjuvant chemotherapy for ascending colon cancer with Lynch syndrome. Although efficacy of 5-FU is not demonstrated in Lynch syndrome, MOSAIC trial had suggested a benefit from FOLFOX compared with 5-FU in patients who have colorectal cancer with Lynch syndrome. Oxaliplatin-based adjuvant chemotherapy can be a therapeutic option for colorectal cancer in lynch syndrome patients.

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease.

Science.gov (United States)

Derikx, Lauranne A A P; Smits, Lisa J T; van Vliet, Shannon; Dekker, Evelien; Aalfs, Cora M; van Kouwen, Mariëtte C A; Nagengast, Fokko M; Nagtegaal, Iris D; Hoogerbrugge, Nicoline; Hoentjen, Frank

2017-03-01

Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by establishing a Lynch syndrome cohort from the Radboud University Medical Center (Nijmegen, The Netherlands) and the Academic Medical Center (Amsterdam, The Netherlands). Patients with heterozygous germline mutations in MLH1, MSH2 (and EPCAM deletion-mediated MSH2 methylation), MSH6, or PMS2 who were tested and/or treated from 1998 through 2014 were included. Patients who developed IBD were identified by linkage of this cohort to the Dutch nationwide Pathology Registry (PALGA). Subsequently, we compared the risk of CRC between Lynch syndrome patients with IBD and without IBD. Of 1046 patients with Lynch syndrome, 15 developed IBD (1.4%). Patients with Lynch syndrome and IBD were significantly younger (median age, 38.0 y) than patients with Lynch syndrome without IBD (median age, 52.0 y; P = .001). Nevertheless, a similar proportion of patients in each group developed CRC: 4 of the 15 patients (26.7%) with Lynch syndrome and IBD compared with 311 of the 1031 patients (30.2%) with Lynch syndrome without IBD. Patients with Lynch syndrome and IBD developed CRC at a younger age (median age, 36.0 y) than patients with Lynch syndrome without IBD (median age, 46.0 y; P = .045). However, the cumulative incidence of CRC was similar between groups (P = .121). All patients with Lynch syndrome and IBD who developed CRC had ulcerative colitis, producing a higher cumulative incidence of CRC for this IBD subgroup (P Lynch syndrome and IBD develop CRC risk at a younger age than patients without IBD; patients with ulcerative colitis are at especially high risk. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Role for Genetic Anticipation in Lynch Syndrome

DEFF Research Database (Denmark)

Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

2009-01-01

PURPOSE: Anticipation (ie, an earlier age at onset in successive generations) is linked to repeat expansion in neurodegenerative syndromes, whereas its role in hereditary cancer is unclear. We assessed anticipation in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), in which DNA...... mismatch repair (MMR) defects cause early and accelerated tumor development with a broad tumor spectrum. PATIENTS AND METHODS: In the population-based Danish HNPCC registry, 407 MMR gene mutation carriers who had developed cancer associated with Lynch syndrome, were identified. These individuals formed 290....... The effect remained when cancers diagnosed at surveillance were excluded, applied to maternal as well as paternal inheritance, and was independent of the MMR gene mutated. CONCLUSION: The effect from anticipation demonstrated in this large, population-based Lynch syndrome cohort underscores the need...

Mutation spectrum in South American Lynch syndrome families

DEFF Research Database (Denmark)

Dominguez-Valentin, Mev; Nilbert, Mef; Wernhoff, Patrik

2013-01-01

Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system.......Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system....

Management of extracolonic tumours in patients with Lynch syndrome

NARCIS (Netherlands)

Koornstra, Jan J; Mourits, Marian Je; Sijmons, Rolf H; Leliveld-Kors, Anna; Hollema, Harry; Kleibeuker, Jan H

Hereditary nonpolyposis colorectal cancer, or Lynch syndrome, is responsible for 2-3% of all colorectal cancers. Lynch syndrome is also associated with a high risk of extracolonic cancers, including endometrial, stomach, small bowel, pancreas, biliary tract, ovary, urinary tract, brain, and skin

Anopheles darlingi and Anopheles marajoara (Diptera: Culicidae susceptibility to pyrethroids in an endemic area of the Brazilian Amazon

Directory of Open Access Journals (Sweden)

Allan Kardec Ribeiro Galardo

2015-12-01

Full Text Available Abstract: INTRODUCTION: This study aimed to evaluate the susceptibility of Anopheles darlingi Root (1926 and Anopheles marajoara Galvão & Damasceno (1942 to pyrethroids used by the National Malaria Control Program in Brazil. METHODS: Mosquitoes from Amapá, Brazilian Amazon, were assessed for resistance to cypermethrin, deltamethrin, and alpha-cypermethrin. Insecticide-impregnated bottles were used as suggested by the CDC/Atlanta. RESULTS: Diagnostic dose for Anopheles darlingi was 12.5µg/bottle during 30 min of exposure. Concentrations for Anopheles marajoara were 20µg/bottle of cypermethrin and deltamethrin and 12.5µg/bottle of alpha-cypermethrin. CONCLUSIONS : No resistance was recorded for Anopheles darlingi , but Anopheles marajoara requires attention.

Especies de Anopheles presentes en el departamento del Putumayo y su infección natural con Plasmodium

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Lorena I. Orjuela

2013-03-01

Full Text Available Introducción. El departamento del Putumayo es una región endémica para malaria, o paludismo, causada principalmente por Plasmodium vivax. Los vectores en esta región incluyen Anopheles darlingi, el cual se ha encontrado solamente en el municipio de Puerto Leguízamo, y recientemente se incriminaron como vectores en Puerto Asís a las especies An. rangeli y An. oswaldoi. Objetivo. El propósito del trabajo fue determinar el papel de An. benarrochi B en la transmisión de malaria en este departamento, ya que se reporta como la especie más abundante que pica a los humanos. Materiales y métodos. Se recolectaron larvas y adultos de Anopheles spp. entre el 2006 y el 2008 en los municipios Puerto Leguízamo y Puerto Asís, y se obtuvieron secuencias del gen ITS-2 y del gen mitocondrial COI para confirmar las determinaciones taxonómicas por morfología. Se practicó la prueba ELISA para establecer la infección por P. vivax y P. falciparum. Resultados. Se identificaron 6.238 individuos correspondientes a 11 especies: An. albitarsis s.l. (1,83 %, An. benarrochi B (72,35 %, An. braziliensis (0,05 %, An. costai (0,06 %, An. darlingi (19,37 %, An. mattogrossensis (0,08 %, An. neomaculipalpus (0,13 %, An. oswaldoi s.l. (0,64 %, An. punctimacula (0,03 %, An. rangeli (5,12 % y An. triannulatus s.l. (0,34 %. Se evaluaron 5.038 adultos por ELISA y 5 se encontraron positivos para P. vivax 210 y VK 247, todos pertenecientes a la especie An. benarrochi B. Conclusión. Los resultados sugieren que An. benarrochi B juega un papel en la transmisión de P. vivax en el departamento de Putumayo, dada su alta atracción por los humanos y su infección natural con Plasmodium spp.   doi: http://dx.doi.org/10.7705/biomedica.v33i1.619

Producción masiva de Romanomermis iyengari (Nematoda: Mermithidae y su aplicación en criaderos de anofelinos en Boa Vista (Roraima, Brasil

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Alberto Santamarina Mijares

2000-03-01

Full Text Available Para desarrollar la producción masiva del nemátodo Romanomermis iyengari Welch, se llevó a cabo el diseño y montaje de una bioplanta en las instalaciones de la Universidad Federal del Estado de Roraima, Brasil, tras un convenio con la Secretaría de Salud del mencionado estado. El objetivo de este trabajo fue establecer el proceso básico de cría masiva del parásito para su posterior aplicación en criaderos de anofelinos. Se obtuvieron 68 cultivos por cada ciclo de siete días, con un total de 272 cultivos por mes. Antes de los tratamientos de campo se realizaron pruebas de laboratorio en las que se comprobó la gran susceptibilidad de las larvas de anofelinos a la infestación por R. iyengari, con tasas de parasitismo de 71 a 98%. Para evaluar la capacidad parasitaria de R. iyengari en condiciones de campo, se seleccionaron 12 criaderos naturales de anofelinos, con áreas que oscilaron entre 50 y 450 m², en los que se observó la presencia de larvas de mosquitos de las especies Anopheles albitarsis Lynch-Arribálzaga y Anopheles rondoni Neiva-Pinto, con densidades de 34 a 66 larvas/m². Para la dispersión del biolarvicida en los 12 criaderos se utilizó una bomba costal manual de fabricación nacional a una presión de dos atmósferas y se aplicó una dosis de 2 000 preparásitos/m². Siete días después de los tratamientos se observó una marcada reducción (85 a 97% de las poblaciones de anofelinos. Los resultados obtenidos demostraron la posibilidad de utilizar R. iyengari para controlar las poblaciones larvarias de ambas especies de anofelinos.

Producción masiva de Romanomermis iyengari (Nematoda: Mermithidae y su aplicación en criaderos de anofelinos en Boa Vista (Roraima, Brasil

Directory of Open Access Journals (Sweden)

Santamarina Mijares Alberto

2000-01-01

Full Text Available Para desarrollar la producción masiva del nemátodo Romanomermis iyengari Welch, se llevó a cabo el diseño y montaje de una bioplanta en las instalaciones de la Universidad Federal del Estado de Roraima, Brasil, tras un convenio con la Secretaría de Salud del mencionado estado. El objetivo de este trabajo fue establecer el proceso básico de cría masiva del parásito para su posterior aplicación en criaderos de anofelinos. Se obtuvieron 68 cultivos por cada ciclo de siete días, con un total de 272 cultivos por mes. Antes de los tratamientos de campo se realizaron pruebas de laboratorio en las que se comprobó la gran susceptibilidad de las larvas de anofelinos a la infestación por R. iyengari, con tasas de parasitismo de 71 a 98%. Para evaluar la capacidad parasitaria de R. iyengari en condiciones de campo, se seleccionaron 12 criaderos naturales de anofelinos, con áreas que oscilaron entre 50 y 450 m², en los que se observó la presencia de larvas de mosquitos de las especies Anopheles albitarsis Lynch-Arribálzaga y Anopheles rondoni Neiva-Pinto, con densidades de 34 a 66 larvas/m². Para la dispersión del biolarvicida en los 12 criaderos se utilizó una bomba costal manual de fabricación nacional a una presión de dos atmósferas y se aplicó una dosis de 2 000 preparásitos/m². Siete días después de los tratamientos se observó una marcada reducción (85 a 97% de las poblaciones de anofelinos. Los resultados obtenidos demostraron la posibilidad de utilizar R. iyengari para controlar las poblaciones larvarias de ambas especies de anofelinos.

Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis.

Science.gov (United States)

Sekine, Shigeki; Mori, Taisuke; Ogawa, Reiko; Tanaka, Masahiro; Yoshida, Hiroshi; Taniguchi, Hirokazu; Nakajima, Takeshi; Sugano, Kokichi; Yoshida, Teruhiko; Kato, Mamoru; Furukawa, Eisaku; Ochiai, Atsushi; Hiraoka, Nobuyoshi

2017-08-01

Lynch syndrome is a cancer predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. MMR deficiency is a ubiquitous feature of Lynch syndrome-associated colorectal adenocarcinomas; however, it remains unclear when the MMR-deficient phenotype is acquired during tumorigenesis. To probe this issue, the present study examined genetic alterations and MMR statuses in Lynch syndrome-associated colorectal adenomas and adenocarcinomas, in comparison with sporadic adenomas. Among the Lynch syndrome-associated colorectal tumors, 68 of 86 adenomas (79%) and all adenocarcinomas were MMR-deficient, whereas all the sporadic adenomas were MMR-proficient, as determined by microsatellite instability testing and immunohistochemistry for MMR proteins. Sequencing analyses identified APC or CTNNB1 mutations in the majority of sporadic adenomas (58/84, 69%) and MMR-proficient Lynch syndrome-associated adenomas (13/18, 72%). However, MMR-deficient Lynch syndrome-associated adenomas had less APC or CTNNB1 mutations (25/68, 37%) and frequent frameshift RNF43 mutations involving mononucleotide repeats (45/68, 66%). Furthermore, frameshift mutations affecting repeat sequences constituted 14 of 26 APC mutations (54%) in MMR-deficient adenomas whereas these frameshift mutations were rare in MMR-proficient adenomas in patients with Lynch syndrome (1/12, 8%) and in sporadic adenomas (3/52, 6%). Lynch syndrome-associated adenocarcinomas exhibited mutation profiles similar to those of MMR-deficient adenomas. Considering that WNT pathway activation sufficiently drives colorectal adenoma formation, the distinct mutation profiles of WNT pathway genes in Lynch syndrome-associated adenomas suggest that MMR deficiency commonly precedes adenoma formation.

Women with double primary cancers of the colorectum and endometrium: do they have Lynch syndrome?

Science.gov (United States)

Song, Taejong; Kim, Min Kyu; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

2016-04-01

The aim of this study was to determine the clinical characteristics of women with double primary cancers of the colorectum and endometrium and assess the probability of Lynch syndrome. We identified 15 women with paraffin-embedded blocks available who were diagnosed, treated and followed for double primary colorectal and endometrial cancers at in a single institution between 1994 and 2014. If there was a family history that met the revised Amsterdam criteria for Lynch syndrome, the woman was considered to have 'clinically defined Lynch syndrome'. If immunohistochemical (IHC) loss of expression of mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) or high microsatellite instability (MSI) was demonstrated in molecular testing, the case was considered 'suspected Lynch syndrome'. The incidence of clinically defined Lynch syndrome according to the revised Amsterdam criteria was 66% (8 of 15). All 8 of the women clinically diagnosed with Lynch syndrome had either abnormal IHC loss or MSI-high, indicating a suspected Lynch syndrome. Furthermore, 27% (4 of 15) experienced second primary colorectal cancer or other Lynch syndrome-related cancers. Overall, 66% (10 of 15) met the criteria for clinically defined Lynch syndrome or suspected Lynch syndrome. Based on our findings, a large percentage (66%) of women with double primary cancers of the colorectum and endometrium are likely to be diagnosed with Lynch syndrome. Copyright © 2015. Published by Elsevier Ireland Ltd.

Lynch syndrome: still not a familiar picture

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Hes Frederik J

2008-02-01

Full Text Available Abstract Background Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems. Case presentation A large Lynch syndrome family with 15 affected family members and involvement in 7 organs is reported. It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients. None of the described family members underwent presymptomatic screening on the basis of the family history. Conclusion Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics. For Lynch syndrome, these features can be found in the Amsterdam and Bethesda criteria. Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family.

PMS2 Involvement in Patients Suspected of Lynch Syndrome

NARCIS (Netherlands)

Niessen, Renee C.; Kleibeuker, Jan H.; Westers, Helga; Jager, Paul O. J.; Rozeveld, Dennie; Bos, Krista K.; Boersma-van Ek, Wytske; Hollema, Harry; Sijmons, Rolf H.; Hofstra, Robert M. W.

It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families. Recently, it was shown that germline mutations in another mismatch repair gene,

DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

Science.gov (United States)

Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

2018-06-08

Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

TumorNext-Lynch-MMR: a comprehensive next generation sequencing assay for the detection of germline and somatic mutations in genes associated with mismatch repair deficiency and Lynch syndrome.

Science.gov (United States)

Gray, Phillip N; Tsai, Pei; Chen, Daniel; Wu, Sitao; Hoo, Jayne; Mu, Wenbo; Li, Bing; Vuong, Huy; Lu, Hsiao-Mei; Batth, Navanjot; Willett, Sara; Uyeda, Lisa; Shah, Swati; Gau, Chia-Ling; Umali, Monalyn; Espenschied, Carin; Janicek, Mike; Brown, Sandra; Margileth, David; Dobrea, Lavinia; Wagman, Lawrence; Rana, Huma; Hall, Michael J; Ross, Theodora; Terdiman, Jonathan; Cullinane, Carey; Ries, Savita; Totten, Ellen; Elliott, Aaron M

2018-04-17

The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer. Moreover, the panel provides microsatellite instability status and detects loss of heterozygosity in the five Lynch genes; MSH2 , MSH6 , MLH1 , PMS2 and EPCAM . Clinical cases are described that highlight the assays ability to differentiate between somatic and germline mutations, precisely classify variants and resolve discordant cases.

Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report.

Science.gov (United States)

Nakamura, Kohei; Nakayama, Kentaro; Minamoto, Toshiko; Ishibashi, Tomoka; Ohnishi, Kaori; Yamashita, Hitomi; Ono, Ruriko; Sasamori, Hiroki; Razia, Sultana; Hossain, Mohammad Mahmud; Kamrunnahar, Shanta; Ishikawa, Masako; Ishikawa, Noriyoshi; Kyo, Satoru

2018-03-25

Lynch syndrome, a hereditary cancer syndrome, occurs because of germline mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1 ( MLH1 ), MutS Homolog 2 ( MSH2 ), MutS Homolog 6 ( MSH6 ), and PMS1 Homolog 2 ( PMS2 )). The disorder is associated with colorectal, endometrial, and other epithelial malignancies, but not cervical cancer. We report a woman with Lynch syndrome with synchronous cervical cancer. This is the first report of Lynch syndrome-related clear cell carcinoma of the cervix, which indicates the possibility of an association between cervical cancer and Lynch syndrome. Suitable genetic tests are required to determine whether common genetics can account for synchronous or subsequent malignancies in Lynch syndrome patients and their families. Such knowledge will also enhance our understanding of the genetic mechanisms governing the development of apparently unrelated cancers.

Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome

DEFF Research Database (Denmark)

Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez-Valentin, Mev

2014-01-01

Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer...... with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic...... ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified...

Metachronous Uterine Endometrioid Adenocarcinoma and Peritoneal Mesothelioma in Lynch Syndrome: A Case Report.

Science.gov (United States)

Lu, Yuxin; Milchgrub, Sara; Khatri, Gaurav; Gopal, Purva

2017-05-01

Lynch syndrome is a hereditary disease with germline mutation in a DNA mismatch repair gene, most often presenting with colorectal and/or endometrial carcinomas; however, the spectrum of Lynch syndrome-associated tumors is expanding. In this article, we report a case of a primary peritoneal epithelioid mesothelioma that developed in a Lynch syndrome patient 10 months after diagnosis of uterine endometrioid adenocarcinoma. To our knowledge, this is the first reported case of a Lynch syndrome patient with metachronous uterine endometrioid adenocarcinoma and primary peritoneal mesothelioma.

Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report

Science.gov (United States)

Nakamura, Kohei; Nakayama, Kentaro; Minamoto, Toshiko; Ishibashi, Tomoka; Ohnishi, Kaori; Yamashita, Hitomi; Ono, Ruriko; Sasamori, Hiroki; Razia, Sultana; Hossain, Mohammad Mahmud; Kamrunnahar, Shanta; Ishikawa, Masako; Ishikawa, Noriyoshi; Kyo, Satoru

2018-01-01

Lynch syndrome, a hereditary cancer syndrome, occurs because of germline mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), MutS Homolog 6 (MSH6), and PMS1 Homolog 2 (PMS2)). The disorder is associated with colorectal, endometrial, and other epithelial malignancies, but not cervical cancer. We report a woman with Lynch syndrome with synchronous cervical cancer. This is the first report of Lynch syndrome-related clear cell carcinoma of the cervix, which indicates the possibility of an association between cervical cancer and Lynch syndrome. Suitable genetic tests are required to determine whether common genetics can account for synchronous or subsequent malignancies in Lynch syndrome patients and their families. Such knowledge will also enhance our understanding of the genetic mechanisms governing the development of apparently unrelated cancers. PMID:29587389

Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report

Directory of Open Access Journals (Sweden)

Kohei Nakamura

2018-03-01

Full Text Available Lynch syndrome, a hereditary cancer syndrome, occurs because of germline mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1 (MLH1, MutS Homolog 2 (MSH2, MutS Homolog 6 (MSH6, and PMS1 Homolog 2 (PMS2. The disorder is associated with colorectal, endometrial, and other epithelial malignancies, but not cervical cancer. We report a woman with Lynch syndrome with synchronous cervical cancer. This is the first report of Lynch syndrome-related clear cell carcinoma of the cervix, which indicates the possibility of an association between cervical cancer and Lynch syndrome. Suitable genetic tests are required to determine whether common genetics can account for synchronous or subsequent malignancies in Lynch syndrome patients and their families. Such knowledge will also enhance our understanding of the genetic mechanisms governing the development of apparently unrelated cancers.

Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions.

Science.gov (United States)

Kravochuck, Sara E; Church, James M

2017-12-01

Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. © 2016 Royal Australasian College of Surgeons.

The Lynch syndrome: a management dilemma.

Science.gov (United States)

Palumbo, Piergaspare; Amatucci, Chiara; Perotti, Bruno; Dezzi, Claudia; Girolami, Marco; Illuminati, Giulio; Angelici, Alberto M

2013-05-01

The case of a familial Lynch syndrome is reported. The criteria for early diagnosis, management and surveillance are briefly reviewed. A germline mutation of genes responsible for mismatch repair is at the basis of the Lynch syndrome. Carriers are predisposed to colorectal cancer and other tumors. Two members of the presently reported family developed colorectal cancer, whereas two others developed other neoplasms. The syndrome was confirmed in members of the same family with appropriate genetic workup. Clinical examination and endoscopy were consequently scheduled once-a-year. Given the high risk of neoplastic disease, such yearly controls can be proposed as the standard follow-up of this condition.

Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database

OpenAIRE

Moller, Pal; Seppala, Toni; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Evans, D. Gareth; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind

2017-01-01

Objective Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance.\\ud \\ud Design We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle rela...

Early onset of colorectal cancer in a 13-year-old girl with Lynch syndrome.

Science.gov (United States)

Ahn, Do Hee; Rho, Jung Hee; Tchah, Hann; Jeon, In-Sang

2016-01-01

Lynch syndrome is the most common inherited colon cancer syndrome. Patients with Lynch syndrome develop a range of cancers including colorectal cancer (CRC) and carry a mutation on one of the mismatched repair (MMR) genes. Although CRC usually occurs after the fourth decade in patients with Lynch syndrome harboring a heterozygous MMR gene mutation, it can occur in children with Lynch syndrome who have a compound heterozygous or homozygous MMR gene mutation. We report a case of CRC in a 13-year-old patient with Lynch syndrome and congenital heart disease. This patient had a heterozygous mutation in MLH1 (an MMR gene), but no compound MMR gene defects, and a K-RAS somatic mutation in the cancer cells.

Recurrence and Variability of Germline EPCAM Deletions in Lynch Syndrome

NARCIS (Netherlands)

Kuiper, Roland P.; Vissers, Lisenka E. L. M.; Venkatachalam, Ramprasath; Bodmer, Danielle; Hoenselaar, Eveline; Goossens, Monique; Haufe, Aline; Kamping, Eveline; Niessen, Renee C.; Hogervorst, Frans B. L.; Gille, Johan J. P.; Redeker, Bert; Tops, Carli M. J.; van Gijn, Marielle E.; van den Ouweland, Ans M. W.; Rahner, Nils; Steinke, Verena; Kahl, Philip; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Stemmler, Susanne; Betz, Beate; Hutter, Pierre; Bunyan, David J.; Syngal, Sapna; Culver, Julie O.; Graham, Tracy; Chan, Tsun L.; Nagtegaal, Iris D.; van Krieken, J. Han J. M.; Schackert, Hans K.; Hoogerbrugge, Nicoline; van Kessel, Ad Geurts; Ligtenberg, Marjolijn J. L.

Recently, we identified 3' end deletions in the EPCAM gene as a novel cause of Lynch syndrome. These truncating EPCAM deletions cause allele-specific epigenetic silencing of the neighboring DNA mismatch repair gene MSH2 in tissues expressing EPCAM. Here we screened a cohort of unexplained Lynch-like

Susceptibility of female Anopheles mosquito to pyrethroid ...

African Journals Online (AJOL)

The detection of insecticides resistance status in a natural population of Anopheles vectors is a vital tool for malaria control intervention strategy against Anopheles gambiae sensu lato, which is the main malaria vector in Nigeria. This study was conducted to determine the susceptibility status of the female Anopheles ...

Systematic immunohistochemical screening for Lynch syndrome in colorectal cancer: a single centre experience of 486 patients.

Science.gov (United States)

Zumstein, Valentin; Vinzens, Fabrizio; Zettl, Andreas; Heinimann, Karl; Koeberle, Dieter; von Flüe, Markus; Bolli, Martin

2016-01-01

Germline mutations in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause autosomal dominantly inherited Lynch syndrome. Lynch syndrome patients and their families benefit from life-saving intensive cancer surveillance. Approximately one in 30 colorectal cancers arises in the setting of Lynch syndrome. The aim of this study was to assess the detection rate of Lynch syndrome at our institution after introduction of systematic immunohistochemical screening for MMR deficiency in colorectal cancers from 2011 to 2015. Following the recommendations by the Evaluation of Genomic Applications in Practice and Prevention working group all colorectal cancers were immunohistochemically stained for the presence of MMR proteins MLH1, PMS2, MSH2 and MSH6, independent of clinical criteria. In the case of loss of MLH1, the somatic BRAF mutation V600E was assessed with molecular testing and/or immunohistochemistry. Clinical follow-up of potential Lynch syndrome carriers (patients with tumours showing loss of MLH1 expression with absence of BRAFV600E, loss of PMS2, MSH2 or MSH6) was evaluated. Of all patients (n = 486), loss of MMR protein expression was found in 73 (15.0%) tumours. Twenty-eight (6.0%) were classified as potential Lynch syndrome carriers. Of the genetically tested potential Lynch syndrome carriers (10 out of 28 patients), 40% were first diagnosed with Lynch syndrome. Implementation of systematic immunohistochemistry screening for Lynch syndrome showed that 6% of colorectal cancers were potentially Lynch-syndrome related. Tumour board protocols should systematically contain information on MMR status of all colorectal cancers and, in MMR deficient cases, include clear recommendations for genetic counselling for all potential Lynch syndrome patients.

Genetics Home Reference: Lynch syndrome

Science.gov (United States)

... Genetic Changes Variations in the MLH1 , MSH2 , MSH6 , PMS2 , or EPCAM gene increase the risk of developing Lynch syndrome . The MLH1 , MSH2 , MSH6 , and PMS2 genes are involved in the repair of errors ...

Lynching Luther

DEFF Research Database (Denmark)

Backe, Hans-Joachim

2016-01-01

, cerebral detective – two character-types traditionally rather juxtaposed as irreconcilable opposites. In this fashion, the overall story arc meshes together elements from Thomas Harris-style serial killer fiction and intuitive detection in the tradition of George Simenon’s Maigret. Similarly......, the individual episodes oscillate between carefully plotted psychology and lurid plot-holes. In other words: taken at face value, Luther is as interesting as it is messy. This paper proposes a reading of Luther that reconciles its many inconsistencies by treating it as if it was a David Lynch movie. If one...

Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome.

Science.gov (United States)

Harper, Holly L; McKenney, Jesse K; Heald, Brandie; Stephenson, Andrew; Campbell, Steven C; Plesec, Thomas; Magi-Galluzzi, Cristina

2017-01-01

Increased risk for upper tract urothelial carcinoma is described in patients with Lynch syndrome, caused by germline mutations in mismatch repair genes. We aimed to identify the frequency of mismatch repair protein loss in upper tract urothelial carcinoma and its potential for identifying an association with Lynch syndrome. We queried our database to identify upper tract urothelial carcinomas. Patients were cross-referenced for history of colorectal carcinoma or other common Lynch syndrome-associated neoplasms to enrich for potential Lynch syndrome cases. Tumor histopathologic characteristics were reviewed and each case was analyzed for loss of mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2, by immunohistochemistry. Of 444 patients with upper tract urothelial carcinoma, a subset of 215 (encompassing 30 with upper tract urothelial carcinoma and another common Lynch syndrome-associated neoplasm) was analyzed for loss of mismatch repair protein expression. Of 30 patients with Lynch syndrome-associated neoplasms, six had documented Lynch syndrome, including two with Muir-Torre syndrome. Mismatch repair protein loss was identified in 7% of total upper tract urothelial carcinomas and 30% of patients with Lynch syndrome-associated neoplasms (including all patients with Lynch syndrome/Muir-Torre syndrome). Of patients without history of Lynch syndrome-associated neoplasms, 5 of 184 (2.7%) had loss of mismatch repair protein expression. Twelve cases with mismatch repair protein loss demonstrated loss of MSH2 and MSH6, and 2 had isolated loss of MSH6. MLH1 and PMS2 expression were consistently retained. Although increased intratumoral lymphocytes, inverted growth, pushing tumor-stromal interface, and lack of nuclear pleomorphism were more commonly seen in cases with mismatch repair protein loss, only intratumoral lymphocytes and presence of pushing borders were statistically significant. MLH1 and PMS2 testing appear to have little utility in upper tract urothelial

Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma.

Science.gov (United States)

Metcalfe, Michael J; Petros, Firas G; Rao, Priya; Mork, Maureen E; Xiao, Lianchun; Broaddus, Russell R; Matin, Surena F

2018-01-01

Patients with Lynch syndrome are at risk for upper tract urothelial carcinoma. We sought to identify the incidence and most reliable means of point of care screening for Lynch syndrome in patients with upper tract urothelial carcinoma. A total of 115 consecutive patients with upper tract urothelial carcinoma without a history of Lynch syndrome were universally screened during followup from January 2013 through July 2016. We evaluated patient and family history using AMS (Amsterdam criteria) I and II, and tumor immunohistochemistry for mismatch repair proteins and microsatellite instability. Patients who were positive for AMS I/II, microsatellite instability or immunohistochemistry were classified as potentially having Lynch syndrome and referred for clinical genetic analysis and counseling. Patients with known Lynch syndrome served as positive controls. Of the 115 patients 16 (13.9%) screened positive for potential Lynch syndrome. Of these patients 7.0% met AMS II criteria, 11.3% had loss of at least 1 mismatch repair protein and 6.0% had high microsatellite instability. All 16 patients were referred for germline testing, 9 completed genetic analysis and counseling, and 6 were confirmed to have Lynch syndrome. All 7 patients with upper tract urothelial carcinoma who had a known history of Lynch syndrome were positive for AMS II criteria and at least a single mismatch repair protein loss while 5 of 6 had high microsatellite instability. We identified 13.9% of upper tract urothelial carcinoma cases as potential Lynch syndrome and 5.2% as confirmed Lynch syndrome at the point of care. These findings have important implications for universal screening of upper tract urothelial carcinoma, representing one of the highest rates of undiagnosed genetic disease in a urological cancer. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of transmission parameters between Anopheles argyritarsis and Anopheles pseudopunctipennis in two ecologically different localities of Bolivia.

Science.gov (United States)

Lardeux, Frédéric; Aliaga, Claudia; Tejerina, Rosenka; Torrez, Libia

2013-08-13

Anopheles (Anopheles) pseudopunctipennis is a recognized malaria vector in the slopes of the Andes of Bolivia. There, other species might be involved in malaria transmission and one candidate could be Anopheles argyritarsis. Although it is generally admitted that this species is not a malaria vector in the neotropical region, its potential role in transmission is still controversial and this situation has to be cleared, at least for Bolivia. Comparing the vectorial efficiency of An. pseudopunctipennis with that of An. argyritarsis could solve the question. The two species were sampled throughout Bolivia to estimate their degree of co-existence in their distribution range. Vectorial efficiencies of the two species were compared in two ecologically different localities where the species were sympatric by analysing their vectorial capacities and components (i e, human biting rates, human biting index, survival, durations of the gonotrophic cycle and extrinsic cycle), and the entomological inoculation rates (EIR). Mosquitoes were sampled monthly during more than one year in the two localities. A monthly sample consisted in hourly captures in four houses (inside and outside) in each locality, during four consecutive nights. Climatic variables (temperature, humidity, potential evapo-transpiration and precipitations) were recorded to better understand variability in the entomological parameters. Relationships were analysed using multivariate methods. Anopheles pseudopunctipennis and An. argyritarsis are "altitude" species, sharing the same geographical distribution range in the Andes of Bolivia. No Plasmodium parasite was identified in An. argyritarsis and estimates of the vectorial capacity indicated that it is not a malaria vector in the two studied localities, unlike An. pseudopunctipennis which showed positive EIRs. This latter species, although not a very good malaria vector, exhibited better life traits values and better behavioural characteristics in favour of

Small-bowel cancer in Lynch syndrome : is it time for surveillance?

NARCIS (Netherlands)

Koornstra, Jan J.; Kleibeuker, Jan H.; Vasen, Hans F. A.

Small-bowel cancer is part of the tumour spectrum of Lynch syndrome. Lynch syndrome, or hereditary non-polyposis colorectal cancer, is caused by germline mutations in one of the mismatch repair genes. Mutation carriers have an estimated lifetime risk for the development of small-bowel cancer of

Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population

DEFF Research Database (Denmark)

Lagerstedt-Robinson, Kristina; Rohlin, Anna; Aravidis, Christos

2016-01-01

Lynch syndrome caused by constitutional mismatch‑repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e., MLH1, MSH2, MSH6 and PMS2...... Lynch syndrome families. These mutations affected MLH1 in 40%, MSH2 in 36%, MSH6 in 18% and PMS2 in 6% of the families. A large variety of mutations were identified with splice site mutations being the most common mutation type in MLH1 and frameshift mutations predominating in MSH2 and MSH6. Large...... deletions of one or several exons accounted for 21% of the mutations in MLH1 and MSH2 and 22% in PMS2, but were rare (4%) in MSH6. In 66% of the Lynch syndrome families the variants identified were private and the effect from founder mutations was limited and predominantly related to a Finnish founder...

Habitat Perkembangbiakan Spesifik Anopheles sp Di Tambang Emas Kura-Kura Banian (Perubahan Perilaku Anopheles sp

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Liestiana Indriyati, SKM

2016-12-01

Full Text Available The results of Health Research 2010, showed that malaria was an infectious disease that the sixth cause of death cause of the sixth of death in Indonesia. Kotabaru is a malaria endemic district, especially in Puskesmas Banian, Annual Parasite Incidence 241.19 in 2014 where the cases of malaria with occurring in illegal gold mines on the slopes of Banian Mountain. It’s needed to know the factors that affect the existence of malaria in these locations. This research was observational study doing by cross-sectional study and analyzed by descriptively. Research conducted at the Gold Mine Banian Buluh Kuning village, Sungai Durian subdistric, Kotabaru district, South Kalimantan Province in February and March, 2015. The activities were catching larva and adult mosquitoes, environmental and mosquito breeding habitats observation and Mass Blood Survey. It was found Anopheles maculatus and Anopheles leucosphyrus with very low densities in area with the number of malaria cases by 22.99%. It was found divers breeding habitats of Anopheles sp on a former gold wash, former drum and former plastic containers. This indicated a behavioral change of Anopheles breeding places because previous to this the Anopheles breed in puddles on the ground or direct contact with the ground.

100 years lynch syndrome

DEFF Research Database (Denmark)

Bleiker, Eveline M A; Esplen, Mary Jane; Meiser, Bettina

2013-01-01

In the care of patients with Lynch Syndrome (LS), a range of psychosocial issues are encountered, which significantly affect patient outcomes. A brief historical background of 'psycho-onco-genetics' (the domain where psychology, oncology and genetics meet) in relation to LS is presented, followed...

Current Hypotheses on How Microsatellite Instability Leads to Enhanced Survival of Lynch Syndrome Patients

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Kristen M. Drescher

2010-01-01

Full Text Available High levels of microsatellite instability (MSI-high are a cardinal feature of colorectal tumors from patients with Lynch Syndrome. Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS colorectal cancer. Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer. In this review we will present the current state of knowledge regarding the mechanisms that are utilized by the host to control colorectal cancer in Lynch Syndrome and why these same mechanisms fail in MSS colorectal cancers.

Current hypotheses on how microsatellite instability leads to enhanced survival of Lynch Syndrome patients.

Science.gov (United States)

Drescher, Kristen M; Sharma, Poonam; Lynch, Henry T

2010-01-01

High levels of microsatellite instability (MSI-high) are a cardinal feature of colorectal tumors from patients with Lynch Syndrome. Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS) colorectal cancer. Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer. In this review we will present the current state of knowledge regarding the mechanisms that are utilized by the host to control colorectal cancer in Lynch Syndrome and why these same mechanisms fail in MSS colorectal cancers.

Merrill Lynch kavandab äridelegatsiooni visiiti Eestisse

Index Scriptorium Estoniae

2000-01-01

Investeerimispanga Merrill Lynch eestvedamisel kavandatakse mais ärimeeste visiiti Eestisse, ütles Jüri Mõis, kes viibis New Yorgis toimunud Maailmapanga seminaril "Omavalitsused rahvusvahelistel kapitaliturgudel"

Colorectal choriocarcinoma in a patient with probable Lynch syndrome

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Viktor Hendrik Koelzer

2016-11-01

Full Text Available Background: Personalized therapy of colorectal cancer (CRC is influenced by morphological, molecular and host-related factors. Here we report the comprehensive clinicopathological and molecular analysis of a pure extra-gestational colorectal choriocarcinoma in a patient with probable Lynch syndrome.Case presentation: A 61 year old female with history of gastric cancer at age 36 presented with a transmurally invasive tumor of the right hemicolon and liver metastasis. A right hemicolectomy was performed. Histopathological analysis showed a mixed trophoblastic and syncytiotrophoblastic differentiation, consistent with choriocarcinoma. Disease progression was rapid under oxaliplatin, capecitabine, irinotecan (XELOXIRI and bevacizumab. Molecular phenotyping identified loss of the mismatch-repair (MMR protein PMS2, microsatellite instability, a lack of MLH1 promoter methylation and lack of of BRAF mutation suggestive of Lynch-Syndrome. Targeted next generation sequencing revealed an Ataxia Telangiectasia Mutated (ATM p.P604S missense mutation. A bleomycin, etoposide and cisplatin (BEP treatment protocol targeting germ-cell neoplasia lead to disease remission and prolonged survival of 34 months.Conclusions: Comprehensive immunohistochemical and genetic testing is essential to identify uncommon cancers possibly related to Lynch syndrome. For rare tumors, personalized therapeutic approaches should take both molecular and morphological information into account.Key words: Colorectal cancer, choriocarcinoma, histopathology, prognostic factors, Lynch syndrome, microsatellite instability, ataxia telangiectasia mutated, molecular pathology, next generation sequencing, personalized medicine

Thyroid cancer in a patient with Lynch syndrome - case report and literature review.

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Fazekas-Lavu, Monika; Parker, Andrew; Spigelman, Allan D; Scott, Rodney J; Epstein, Richard J; Jensen, Michael; Samaras, Katherine

2017-01-01

Lynch syndrome describes a familial cancer syndrome comprising germline mutations in one of four DNA mismatch repair genes, MLH1 , MSH2 , MSH6 , and PMS2 and is characterized by colorectal, endometrial, and other epithelial malignancies. Thyroid cancer is not usually considered to be part of the constellation of Lynch syndrome cancers nor have Lynch syndrome tumor gene mutations been reported in thyroid malignancies. This study reports a woman with Lynch syndrome (colonic cancer and a DNA mismatch repair mutation in the MSH2 gene) with a synchronous papillary thyroid cancer. Six years later, she developed metachronous breast cancer. Metastatic bone disease developed after 3 years, and the disease burden was due to both breast and thyroid diseases. Despite multiple interventions for both metastatic breast and thyroid diseases, the patient's metastatic burden progressed and she died of leptomeningeal metastatic disease. Two prior case reports suggested thyroid cancer may be an extraintestinal malignancy of the Lynch syndrome cancer group. Hence, this study examined the genetic relationship between the patient's known Lynch syndrome and her thyroid cancer. The thyroid cancer tissue showed normal expression of MSH2 , suggesting that the tumor was not due to the oncogenic mutation of Lynch syndrome, and molecular analysis confirmed BRAF V600E mutation. Although in this case the thyroid cancer was sporadic, it raises the importance of considering cancer genetics in familial cancer syndromes when other cancers do not fit the criteria of the syndrome. Careful documentation of other malignancies in patients with thyroid cancer and their families would assist in better understanding of any potential association. Appropriate genetic testing will clarify whether a common pathogenic mechanism links seemingly unrelated cancers.

The Course of Law: State Intervention in Southern Lynch Mob Violence 1882–1930

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Kinga Makovi

2016-09-01

Full Text Available Collective violence when framed by its perpetrators as "citizen" justice is inherently a challenge to state legitimacy. To properly account for such violence, it is necessary to consider an opportunity structure incorporating the actions of both vigilantes and agents of the state. The motivation and lethality of lynch mobs in the South cannot be understood without considering how the state reacted to the legitimacy challenges posed by lynching. We trace the shifting orientation of state agents to lynching attempts between the end of Reconstruction and the start of the Great Depression. Analyzing an inventory of more than 1,000 averted and completed lynching events in three Southern states, we model geographic and temporal patterns in the determinants of mob formation, state intervention, and intervention success. Opponents of lynching often pled with mobs to "let the law take its course." This article examines the course followed by the law itself, as state actors moved between encouraging, accommodating, and in many instances averting mob violence.

HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME PADA WANITA UMUR 16 TAHUN

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Asril Zahari

2011-09-01

Full Text Available AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC/Lynch

[Mosquitos of peri and extradomiciliary environments in the southern region of Brazil].

Science.gov (United States)

Teodoro, U; Guilherme, A L; Lozovei, A L; La Salvia Filho, V; Sampaio, A A; Spinosa, R P; Ferreira, M E; Barbosa, O C; de Lima, E M

1994-04-01

Mosquitoes were collected on Sonho Real farm, Querência do Norte county, Paraná State, Brazil, using human bait and Falcão traps between June 1989 and May 1990. The fauna composition, monthly density, hours of major density, human attraction and presence of mosquitoes in domestic animal shelters were investigated. 5,923 mosquitoes of the genera Aedes, Aedomyia, Anopheles, Coquillettidea, Culex, Mansonia, Psorophora, Sabethes and Uranotaenia were collected. 33 species of mosquitoes were identified and among them Aedes scapularis, Anopheles albitarsis, Aedomyia squamipennis, Coquillettidea lynchi, Mansonia titillans e Coquillettidea venezuelensis were predominant. All these species were captured mainly on human bait, except Aedomyia squamipennis that was captured in domestic animal shelters. With regard to all the mosquitoes captured (5,923), their major period of activity was between 18 and 19 hours and April was the month of greatest density.

A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome

DEFF Research Database (Denmark)

Clendenning, Mark; Senter, Leigha; Hampel, Heather

2008-01-01

BACKGROUND: When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within PMS2 has been limited (Lynch syndrome cases...... on immunohistochemical analysis. RESULTS: We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n=61). These individuals all display the rare allele (population...... and Swedish ancestry. We estimate that there are >10,000 carriers of this mutation in the United States alone. The identification of both the mutation and the common haplotype in one Swedish control sample (n = 225), along with evidence that Lynch syndrome associated cancers are rarer than expected...

Fertility and apparent genetic anticipation in Lynch syndrome.

Science.gov (United States)

Stupart, Douglas; Win, Aung Ko; Jenkins, Mark; Winship, Ingrid M; Goldberg, Paul; Ramesar, Rajkumar

2014-09-01

Genetic anticipation is the phenomenon in which age of onset of an inherited disorder decreases in successive generations. Inconsistent evidence suggests that this occurs in Lynch syndrome. A possible cause for apparent anticipation is fecundity bias, which occurs if the disease adversely affects fertility. The purpose of this study was to determine the effect of age of diagnosis of colorectal cancer (CRC) on lifetime fertility in Lynch syndrome, and whether this can falsely create the appearance of genetic anticipation. A computer model simulated age of diagnosis of CRC in hypothetical Lynch syndrome carriers and their offspring. The model assumed similar age distribution of CRC across generations (i.e. that there was no true anticipation). Age distribution of CRC diagnosis, and lifetime fertility rates (grouped by age of diagnosis of CRC) were determined from the Australasian Colorectal Cancer Family Registry (ACCFR). Apparent anticipation was calculated by comparing ages of diagnosis of CRC in affected parent-child pairs. A total of 1,088 patients with CRC were identified from the ACCFR. Total lifetime (cohort) fertility was related to age of diagnosis of CRC (correlation coefficient 0.13, P = 0.0001). In the simulation, apparent anticipation was 1.8 ± 0.54 years (P = 0.0044). Observed apparent anticipation in the ACCFR cohort was 4.8 ± 1.73 years (P = 0.0064). There was no difference in apparent anticipation between the simulate d and observed parent-child pairs (P = 0.89). The appearance of genetic anticipation in Lynch syndrome can be falsely created due to changes in fertility.

The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

Science.gov (United States)

Cohen, Stephanie A; Leininger, Anna

2014-01-01

Lynch syndrome is the most common cause of hereditary colon cancer, and accounts for as much as 3% of all colon and endometrial cancers. The identification and management of individuals with Lynch syndrome have evolved over the past 20 years, yet the syndrome remains vastly underdiagnosed. It is important for clinicians to recognize individuals and families who are at risk in order to be able to manage them appropriately and reduce their morbidity and mortality from this condition. This review will touch on the history of Lynch syndrome, the current knowledge of genotype–phenotype correlations, the cancers associated with Lynch syndrome, and management of individuals who are gene carriers. PMID:25161364

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease

NARCIS (Netherlands)

Derikx, L.A.A.P.; Smits, L.J.T.; Lent-van Vliet, S. van; Dekker, E.; Aalfs, C.M.; Kouwen, M.C.A. van; Nagengast, F.M.; Nagtegaal, I.D.; Hoogerbrugge, N.; Hoentjen, F.

2017-01-01

Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by

Man biting rate seasonal variation of malaria vectors in Roraima, Brazil

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Fábio Saito Monteiro de Barros

2007-06-01

Full Text Available Malaria control has been directed towards regional actions where more detailed knowledge of local determinants of transmission is of primary importance. This is a short report on range distribution and biting indices for Anopheles darlingi and An. albitarsis during the dry and rainy season that follows river level variation in a savanna/alluvial forest malaria system area in the Northern Amazon Basin. Distribution range and adult biting indices were at their highest during the rainy season for both An. darlingi and An. albitarsis. During the rainy season the neighboring alluvial forest was extensively flooded. This coincided with highest rates in malaria transmission with case clustering near the river. As the river receded, anopheline distribution range and density decreased. This decrease in distribution and density corresponded to a malaria decrease in the near area. An exponential regression function was derived to permit estimations of An. darlingi distribution over specified distances. Anopheline spatio-temporal variations lead to uneven malaria case distribution and are of important implications for control strategies.

Diagnosing lynch syndrome in absence of colorectal cancer.

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Lynch, Henry T; Knezetic, Joseph; Lanspa, Stephen

2012-11-01

There are many ways in which a diagnosis of Lynch syndrome can be made, most prominent of which is family history, presence of cancer, high microsatellite instability, immunohistochemistry, and a mismatch repair germline mutation. There are at least four molecular pathways for colorectal cancer carcinogenesis: 1) adenoma-carcinoma sequence; 2) hereditary microsatellite instability; 3) serrated pathway; 4) epidermal growth factor receptor. The answer to diagnosing Lynch syndrome in the absence of colorectal cancer may be partially based upon the phenotypic characteristics of the colonic polyps should they be identified at colonoscopy, specifically their phenotypic characteristics of location, size, histology, number, and age of polyp onset.

Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

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Erten, Mujde Z; Fernandez, Luca P; Ng, Hank K; McKinnon, Wendy C; Heald, Brandie; Koliba, Christopher J; Greenblatt, Marc S

2016-10-01

Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. We compared targeted versus universal screening of CRCs for Lynch syndrome. In 2010-2011, we employed targeted screening (age Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

Physico-chemical characteristics of Anopheles breeding sites ...

African Journals Online (AJOL)

ELO

analysis of the physicochemical parameters of the water samples was carried out in the Nigerian ... Key words: Malaria, Anopheles mosquitoes, breeding habitat, physico-chemical properties. ... Anopheles mosquito has been found to breed in.

[Colorectal Carcinoma with Suspected Lynch Syndrome: A Multidisciplinary Algorithm].

Science.gov (United States)

Schneider, R; Schneider, C; Büttner, R; Reinacher-Schick, A; Tannapfel, A; Fürst, A; Rüschoff, J; Jakobeit, C; Royer-Pokora, B; Möslein, G

2015-12-01

Lynch syndrome is the most frequent hereditary cancer syndrome, accounting for approximately 3-5 % of all colorectal cancers. In addition, it is the most frequent predisposing hereditary cause of endometrial cancer and is also associated with gastric cancer, ovarian cancer, cancer of the urinary tract as well as several other cancers. In clinical practise Lynch syndrome is frequently not detected and many clinicians admit uncertainties regarding diagnostic procedures. Also, counselling of patients is considered difficult regarding therapeutic - especially prophylactic surgical and chemopreventive options and recommendations. Based on a review of available literature we discuss optimized strategies for improved detection of suspected Lynch syndrome patients. The aim of this review is to establish a clinical algorithm of how to proceed on a diagnostic level and to discuss surgical options at the time of a colorectal cancer. In order to identify patients with Lynch syndrome, family history should be ascertained and evaluated in regards to fulfilment of the Amsterdam-II- and/or the revised Bethesda criteria. Subsequently immunohistochemical staining for the mismatch-repair-genes, BRAF testing for MLH1 loss of expression, as well as testing for microsatellite instability in some, followed by genetic counselling and mutation analysis when indicated, is recommended. Pathological identification of suspected Lynch syndrome is readily feasible and straightforward. However, the need of performing these analyses in the tumor biopsy at the time of (gastroenterological) diagnosis of CRC neoplasia is essential, in order to offer patients the option of a prophylactically extended surgery and - as recommended in the German S3 guidelines - to discuss the option of a merely prophylactical hysterectomy and oophorectomy (if postmenopausal) in women. Close cooperation between gastroenterologists, pathologists and surgeons is warranted, so that patients may benefit from options of

CTNNB1-mutant colorectal carcinomas with immediate invasive growth: a model of interval cancers in Lynch syndrome.

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Ahadova, Aysel; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

2016-10-01

The implementation of regular colonoscopy programs has significantly decreased the mortality associated with colorectal cancer (CRC) in Lynch syndrome patients. However, interval CRCs in Lynch syndrome that remain undetected by colonoscopy still represent a substantial problem in the management of the syndrome. One possible reason of interval cancers could be a non-polypous pathway of cancer development. To examine the possibility of a non-polypous pathway of CRC development in Lynch syndrome, we analyzed the histological appearance of 46 Lynch syndrome-associated CRCs and compared them to 34 sporadic microsatellite unstable cancers. We observed that 25 (62.5 %) out of 40 assessable Lynch syndrome-associated carcinomas lacked evidence of polypous growth, compared to 17 (50 %) out of 34 sporadic MSI-H cancers. We detected CTNNB1 mutations in 8 (17.4 %) out of 46 Lynch syndrome-associated cancers compared to 0 out of 34 sporadic MSI-H cancers (p = 0.01). The majority of CTNNB1-mutant cancers presented with a histological appearance suggesting immediate invasive growth. Our results suggest that a distinct subgroup of CRCs in Lynch syndrome may in fact emerge from a non-polypous precursor, thus potentially explaining the phenomenon of interval cancers. Such a non-polypous precursor may be the recently described mismatch repair-deficient crypt focus, which remains invisible for the examiner during colonoscopy. This calls for considering the implementation of active, primary preventive measures in the management of Lynch syndrome. Future studies on pathogenic pathways and precursor lesions in Lynch syndrome are strongly encouraged, and the clinical efficacy of new prevention approaches should be evaluated in prospective clinical trials.

Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations

DEFF Research Database (Denmark)

Nielsen, Sofie V,; Stein, Amelie; Dinitzen, Alexander B.

2017-01-01

selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than...... and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases....

Is there a role for prophylactic colectomy in Lynch syndrome patients with inflammatory bowel disease?

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McNamara, Kate L; Aronson, Melyssa D; Cohen, Zane

2016-01-01

Lynch syndrome and chronic inflammatory bowel disease are two important risk factors for colorectal cancer. It is unclear whether Lynch syndrome patients with inflammatory bowel disease are at sufficiently increased risk for colorectal cancer to warrant prophylactic colectomy. This study aims to identify all cases of Lynch syndrome and concurrent inflammatory bowel disease in a large familial gastrointestinal cancer registry, define incidence of colorectal cancer, and characterize mismatch repair protein gene mutation status and inflammatory bowel disease-associated colorectal cancer risk factors. We retrospectively identified and collected clinical data for all cases with confirmed diagnoses of Lynch syndrome and inflammatory bowel disease in the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital in Toronto, Canada. Twelve cases of confirmed Lynch syndrome, and concurrent inflammatory bowel disease were identified. Four cases developed colorectal cancer. An additional five cases had colectomy; one was performed for severe colitis, and four were performed for low-grade dysplasia. None of these surgical specimens contained malignancy or high-grade dysplasia. The presentation of Lynch syndrome with inflammatory bowel disease is uncommon and not well described in the literature. This small but important series of twelve cases is the largest reported to date. In this series, patients with Lynch syndrome and concurrent inflammatory bowel disease do not appear to have sufficiently increased risk for colorectal cancer to recommend prophylactic surgery. Therefore, the decision to surgery should continue to be guided by surgical indications for each disease. Further evaluation of this important area will require multi-institutional input.

Demasculinization of the Anopheles gambiae X chromosome

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Magnusson Kalle

2012-05-01

Full Text Available Abstract Background In a number of organisms sex-biased genes are non-randomly distributed between autosomes and the shared sex chromosome X (or Z. Studies on Anopheles gambiae have produced conflicting results regarding the underrepresentation of male-biased genes on the X chromosome and it is unclear to what extent sexual antagonism, dosage compensation or X-inactivation in the male germline, the evolutionary forces that have been suggested to affect the chromosomal distribution of sex-biased genes, are operational in Anopheles. Results We performed a meta-analysis of sex-biased gene expression in Anopheles gambiae which provides evidence for a general underrepresentation of male-biased genes on the X-chromosome that increased in significance with the observed degree of sex-bias. A phylogenomic comparison between Drosophila melanogaster, Aedes aegypti and Culex quinquefasciatus also indicates that the Anopheles X chromosome strongly disfavours the evolutionary conservation of male-biased expression and that novel male-biased genes are more likely to arise on autosomes. Finally, we demonstrate experimentally that transgenes situated on the Anopheles gambiae X chromosome are transcriptionally silenced in the male germline. Conclusion The data presented here support the hypothesis that the observed demasculinization of the Anopheles X chromosome is driven by X-chromosome inactivation in the male germline and by sexual antagonism. The demasculinization appears to be the consequence of a loss of male-biased expression, rather than a failure in the establishment or the extinction of male-biased genes.

Twenty hanging Dolls and a Lynching:

DEFF Research Database (Denmark)

Risør, Helene

2010-01-01

The article sets lynching of presumed criminals in the city of El Alto, Bolivia, in relation to both everyday experiences of insecurity about crime and violence and the enactment of neighborliness as a grounded notion of citizenship. Focusing on the experience and management of insecurity and its...

Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer.

Science.gov (United States)

Takeda, Takashi; Tsuji, Kosuke; Banno, Kouji; Yanokura, Megumi; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke

2018-05-01

Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM₅ were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM₅, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Targeted Screening With Combined Age- and Morphology-Based Criteria Enriches Detection of Lynch Syndrome in Endometrial Cancer.

Science.gov (United States)

Lin, Douglas I; Hecht, Jonathan L

2016-06-01

Endometrial cancer is associated with Lynch syndrome in 2% to 6% of cases. Adequate screening may prevent of a second cancer and incident cancers in family members via risk-reducing strategies. The goal of the study was to evaluate the detection rate of Lynch syndrome via a targeted screening approach. In 2009, we incorporated targeted Lynch syndrome screening via immunohistochemistry for MLH1, PMS2, MSH2, and MSH6, followed by MLH1 promoter hypermethylation, in select cases of endometrial carcinoma. Criteria for patient selection included (1) all patients Lynch syndrome. Therefore, targeted screening with combined age and morphology based criteria enriches detection of Lynch syndrome in endometrial cancer. However, the detection rate is lower than the rates from published series that offer universal screening. © The Author(s) 2016.

morphological identification of malaria vectors within anopheles

African Journals Online (AJOL)

DR. AMIN

Africa among the human population. Determination of risk of malaria transmission requires quick and accurate methods of identification of Anopheles mosquitoes especially when targeting vector control. (Maxwell, et al., 2003). Anopheles mosquito transmits malaria. The most important vectors of malaria are members of.

The identification of Lynch syndrome in Congolese colorectal cancer patients.

Science.gov (United States)

Poaty, Henriette; Aba Gandzion, Chandra; Soubeyran, Isabelle; Gassaye, Déby; Peko, Jean Félix; Nkoua Bon, Jean Bernard; Gombé Mbalawa, Charles

2017-10-01

We aimed to investigate the prevalence of Lynch syndrome as one of hereditary causes of colorectal cancer (CRC) among young Congolese individuals affected by the CRC, and to define methods for diagnosis in Congo Brazzaville. We conducted a transversal cohort study of 34 patients having a CRC with a family history for a period of eight years. They were selected among 89 CRCs of any type from the Bethesda guidelines criteria combined with pedigrees. Mismatch repair (MMR) genes alterations were researched by immunohistochemistry (IHC). We identified with the Bethesda criteria a total of 38.2% (34/89) patients having familial CRC with a confidence interval (CI) of 95%=[0.34-0.41]. Only 14.7% (5/34) 95% CI=[0.34-2.32] patients showed MMR immunodeficiency involving firstly MLH1 protein then MSH2 protein. These data account for 5.6% (5/89) 95% CI=[0.15-0.33] of patients affected by Lynch syndrome with an earlier median age of 35 years (range 20 to 47 years). The prevalence of Lynch syndrome found in Brazzaville is comparable to that is found in northern countries. The combined Bethesda guidelines, pedigree and IHC is an accessible and good alternative method for the positive diagnosis of Lynch syndrome in current practice in Congo. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Value-based healthcare in Lynch syndrome

NARCIS (Netherlands)

Hennink, Simone D; Hofland, N.; Gopie, J.P.; van der Kaa, C.; de Koning, K.; Nielsen, M.; Tops, C.; Morreau, H.; de Vos Tot Nederveen Cappel, W.H.; Langers, A.M.; Hardwick, J.C.; Gaarenstroom, K.N.; Tollenaar, R.A.; Veenendaal, R.A.; Tibben, A.; Wijnen, J.; van Heck, M.; van Asperen, C.; Roukema, J.A.; Hommes, D.W.; Hes, F.J.; Vasen, H.F.A.

2013-01-01

Lynch syndrome (LS), one of the most frequent forms of hereditary colorectal cancer (CRC), is caused by a defect in one of the mismatch repair (MMR) genes. Carriers of MMR defects have a strongly increased risk of developing CRC and endometrial cancer. Over the last few years, value-based healthcare

Biting behavior of Anopheles mosquitoes in Costa Marques, Rondonia, Brazil

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Terry A. Klein

1991-03-01

Full Text Available Mosquito collections were made in and near Costa Marques, Rondonia, Brazil, to determine anopheline anthropophilic/zoophilic behavior. Collections from a non-illuminated, bovine-baited trap and indoor and outdoor human-bait collections were compared. Anopheles darlingi and Anopheles deaneorum were more anthropophilic than the other anophelines collected. The remainder of the Anopheles species were collected much morefrequently in bovine-baited traps than in human-bait collections. Anopheles darlingi and An. deaneorum were more frequently collected inside houses than the other anopheline species. But, when collections were made in a house with numerous openings in the walls, there were few differences in the percentages of each species biting man indoors versus outdoors. Anopheles darlingi was the predominant mosquito collected, both inside and outside houses, and had the strongest anthropophilic feeding behavior of the anophelines present.Para determinar o comportamento antropofilico e zoofilico dos anofelinos, foram capturados mosquitos na periferia e na zona urbana de Costa Marques, Rondônia, Brasil. Foram comparadas as capturas feitas à noite, com iscas bovinas e humanas, dentro efora de casa. O Anopheles darlingi e o Anopheles deaneorumforam mais antropojilicos do que os outros anofelinos capturados. O restante das espécies anofelinas foi capturado mais freqüentemente nas iscas bovinas do que nas humanas. Anopheles darlingi e Anopheles deaneorumforam capturados dentro de casa com mais freqüência do que as outras espécies anofelinas. Porém, quando a captura foi feita em casas com muitas aberturas nas paredes houve pouca diferença nas porcentagens de cada espécie sugadora de humanos dentro efora de casa. Anopheles darlingi foi o mosquito capturado com mais freqüência, dentro e fora de casa, e apresentava maior antropofilia em relação aos outros anofelinos presentes.

BIONOMY OF Anopheles punctulatus GROUP (Anopheles farauti, Anopheles koliensis, Anopheles punctulatus MALARIA VECTOR IN PAPUA PROVINCE

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Semuel Sandy

2014-08-01

Full Text Available ABSTRAKMalaria merupakan masalah kesehatan utama di Provinsi Papua dengan angka Annual Parasite Incidence (API padatahun 2011 sebesar 58 per 1000 penduduk dan Annual Malaria Incidence (AMI sebesar 169 per 1000 penduduk. Vektormalaria Papua dilaporkan Anopheles farauti, An. punctulatus dan An. koliensis. Tiga spesies tersebut aktif menggigit padamalam hari (nokturnal, antropofilik dengan karakteristik tempat perkembangbiakan, aktifitas menggigit, dan tempatistirahat dilaporkan spesifik setiap spesies. Kajian ini untuk melihat beberapa aspek bionomi (tempat perkembangbiakan,aktifitas menggigit, dan tempat istirahat. Larva An. farauti memiliki habitat di daerah pantai, perairan payau (memilikitoleransi terhadap salinitas 4,6%, irigasi buatan atau alami. Nyamuk dewasa An. farauti betina bersifat nokturnal,eksofagik, eksofilik, dan antropofilik. Larva An. koliensis tidak ditemukan di perairan payau, banyak ditemukan di hutanrawa, hutan sagu, kolam semi permanen atau permanen yang dangkal dan terpapar sinar matahari langsung. Nyamukdewasa An. koliensis bersifat nokturnal, antropofilik (78% menggigit manusia, eksofagik, eksofilik sedangkan larva An.punctulatus tidak ditemukan di air payau, tetapi ditemukan pada kolam dengan air jernih atau keruh dengan vegetasi atautanpa vegetasi air. Larva An. punctulatus juga ditemukan di hutan sagu dan hutan rawa dengan paparan sinar mataharilangsung. Nyamuk dewasa An. punctulatus bersifat nokturnal, antropofilik (98% menggigit manusia, eksofagik, endofilik.Data dasar mengenai perilaku nyamuk Anopheles (bionomi sangat diperlukan dalam mengembangkan pola intervensi dankontrol vektor yang lebih efektif dan efisien.Kata kunci: vektor malaria, An. punctulatus group, bionomi, PapuaABSTRACTMalaria is a major health problem in Papua province with Annual Parasite Incidence (API was reported 58/1000population in 2011, and the Annual Malaria Incidence (AMI was 169/1000 population. The malaria vector in Papua wereAnopheles

Vector competence of Anopheles and Culex mosquitoes for Zika virus

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Brittany L. Dodson

2017-03-01

Full Text Available Zika virus is a newly emergent mosquito-borne flavivirus that has caused recent large outbreaks in the new world, leading to dramatic increases in serious disease pathology including Guillain-Barre syndrome, newborn microcephaly, and infant brain damage. Although Aedes mosquitoes are thought to be the primary mosquito species driving infection, the virus has been isolated from dozens of mosquito species, including Culex and Anopheles species, and we lack a thorough understanding of which mosquito species to target for vector control. We exposed Anopheles gambiae, Anopheles stephensi, and Culex quinquefasciatus mosquitoes to blood meals supplemented with two Zika virus strains. Mosquito bodies, legs, and saliva were collected five, seven, and 14 days post blood meal and tested for infectious virus by plaque assay. Regardless of titer, virus strain, or timepoint, Anopheles gambiae, Anopheles stephensi, and Culex quinquefasciatus mosquitoes were refractory to Zika virus infection. We conclude that Anopheles gambiae, Anopheles stephensi, and Culex quinquefasciatus mosquitoes likely do not contribute significantly to Zika virus transmission to humans. However, future studies should continue to explore the potential for other novel potential vectors to transmit the virus.

Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome

DEFF Research Database (Denmark)

Burn, John; Bishop, D Timothy; Mecklin, Jukka-Pekka

2008-01-01

BACKGROUND: Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect...... on the colon. METHODS: In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome...... on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.)...

Qualitative Study Of Anopheles Species In Konduga Lake Area Of ...

African Journals Online (AJOL)

The investigation on Anopheles species in Konduga lake area, Borno State of Nigeria, was carried out to identify various Anopheles species prevalent in the area and to determine their relative population densities. Six Anopheles species were recorded, namely, A. gambiae, A. funestus, A. ziemanni, A. squamosus, ...

What the physician needs to know about Lynch syndrome: an update.

Science.gov (United States)

Lynch, Henry T; Lynch, Jane F

2005-04-01

The Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), is the most common form of hereditary colorectal cancer (CRC), accounting for 2% to 7% of all CRC cases. The next most common hereditary CRC syndrome is familial adenomatous polyposis (FAP), which accounts for less than 1% of all CRC. Lynch syndrome is of crucial clinical importance due to the fact that it predicts the lifetime risk for CRC and a litany of extra-CRC cancers (of the endometrium, ovary, stomach, small bowel, hepatobiliary tract, upper uroepithelial tract, and brain) through assessment of a well-orchestrated family history. A Lynch syndrome diagnosis is almost certain when a mutation in a mismatch repair gene--most commonly MSH2, MLHI, or, to a lesser degree, MSH6--is identified. Once diagnosed, the potential for significant reduction in cancer-related morbidity and mortality through highly targeted surveillance may be profound. Particularly important is colonoscopy initiated at an early age (ie, 25 years) and repeated annually due to accelerated carcinogenesis. In women, endometrial aspiration biopsy and transvaginal ultrasound are important given the extraordinarily high risk for endometrial and ovarian carcinoma. These cancer control strategies have a major impact on at-risk family members once they have been counseled and educated thoroughly about Lynch syndrome's natural history and their own hereditary cancer risk.

Factors affecting fungus-induced larval mortality in Anopheles gambiae and Anopheles stephensi

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Takken Willem

2010-01-01

Full Text Available Abstract Background Entomopathogenic fungi have shown great potential for the control of adult malaria vectors. However, their ability to control aquatic stages of anopheline vectors remains largely unexplored. Therefore, how larval characteristics (Anopheles species, age and larval density, fungus (species and concentration and environmental effects (exposure duration and food availability influence larval mortality caused by fungus, was studied. Methods Laboratory bioassays were performed on the larval stages of Anopheles gambiae and Anopheles stephensi with spores of two fungus species, Metarhizium anisopliae and Beauveria bassiana. For various larval and fungal characteristics and environmental effects the time to death was determined and survival curves established. These curves were compared by Kaplan Meier and Cox regression analyses. Results Beauveria bassiana and Metarhizium anisopliae caused high mortality of An. gambiae and An. stephensi larvae. However, Beauveria bassiana was less effective (Hazard ratio (HR Metarhizium anisopliae. Anopheles stephensi and An. gambiae were equally susceptible to each fungus. Older larvae were less likely to die than young larvae (HR Conclusions This study shows that both fungus species have potential to kill mosquitoes in the larval stage, and that mortality rate depends on fungus species itself, larval stage targeted, larval density and amount of nutrients available to the larvae. Increasing the concentration of fungal spores or reducing the exposure time to spores did not show a proportional increase and decrease in mortality rate, respectively, because the spores clumped together. As a result spores did not provide uniform coverage over space and time. It is, therefore, necessary to develop a formulation that allows the spores to spread over the water surface. Apart from formulation appropriate delivery methods are also necessary to avoid exposing non-target organisms to fungus.

The B-Lynch uterine brace suture, and a bit of this and a bit of that...

Science.gov (United States)

Karoshi, Mahantesh

2010-03-01

The widespread application of the B-Lynch brace suture to control postpartum hemorrhage has sparked interest in a variety of adjunctive methods, used alone or in combination, to control uterine bleeding. Although the B-Lynch brace suture has been used with good results throughout the world, failures can and do occur in rare instances, especially when the suture is incorrectly placed for use for an inappropriate indication. Four reports of additional methods to control postpartum hemorrhage are published in this issue of IJGO. Three use the B-Lynch brace suture combined with other techniques. The need for additional techniques reminds the reader of the importance of proper suture application for proper indication. Potential reasons for failure of the B-Lynch suture are provided.

How does genetic risk information for Lynch syndrome translate to risk management behaviours?

Science.gov (United States)

Steel, Emma; Robbins, Andrew; Jenkins, Mark; Flander, Louisa; Gaff, Clara; Keogh, Louise

2017-01-01

There is limited research on why some individuals who have undergone predictive genetic testing for Lynch syndrome do not adhere to screening recommendations. This study aimed to explore qualitatively how Lynch syndrome non-carriers and carriers translate genetic risk information and advice to decisions about risk managment behaviours in the Australian healthcare system. Participants of the Australasian Colorectal Cancer Family Registry who had undergone predictive genetic testing for Lynch syndrome were interviewed on their risk management behaviours. Transcripts were analysed thematically using a comparative coding analysis. Thirty-three people were interviewed. Of the non-carriers ( n  = 16), 2 reported having apparently unnecessary colonoscopies, and 6 were unsure about what population-based colorectal cancer screening entails. Of the carriers ( n  = 17), 2 reported they had not had regular colonoscopies, and spoke about their discomfort with the screening process and a lack of faith in the procedure's ability to reduce their risk of developing colorectal cancer. Of the female carriers ( n  = 9), 2 could not recall being informed about the associated risk of gynaecological cancers. Non-carriers and female carriers of Lynch syndrome could benefit from further clarity and advice about appropriate risk management options. For those carriers who did not adhere to colonoscopy screening, a lack of faith in both genetic test results and screening were evident. It is essential that consistent advice is offered to both carriers and non-carriers of Lynch syndrome.

EKOLOGI Anopheles spp. DI KABUPATEN LOMBOK TENGAH

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Majematang Mading

2014-07-01

Full Text Available Malaria remains a public health problem in West Nusa Tenggara Province. Central Lombok District is one of the areas with high case of malaria. Annual Malaria Incidence (AMI was increased from 5.9 ‰ in 2006, 6.7‰ up to 8.1‰ in 2008. The objective of the study is to describe the ecological condition of Anopheles spp. through observation, measurement of environmental variables, larvae and adult collection. This research was an observational research with cross-sectional study. The population of this study is all mosquitos and breeding habitats of Anopheles spp. that exist in the research location. Ecological observations carried out on anopheles breeding habitats including acidity, salinity, shaded places and aquatic biota. Air temperature and humidity measured at the adult mosquitoes trapping sites. The result showed that pH values of water is around 9.00, salinity in the breeding habitats around 14 ppm, and water biota (i.e. moss, grass, shrimps, fishes, tadpoles and crabs surrounded by bushes with larvae density 0,1-28,8 each dipping. The air measurement at the time was between 23°-27° Celsius and 65%-84% humidity. This research concludes that ecology and environmental conditions were supporting the development of larvae and adult mosquito of Anopheles spp.Keywords: ecology, Anopheles spp., Central Lombok

The clinical phenotype of Lynch syndrome due to germline PMS2 mutations

Science.gov (United States)

Senter, Leigha; Clendenning, Mark; Sotamaa, Kaisa; Hampel, Heather; Green, Jane; Potter, John D.; Lindblom, Annika; Lagerstedt, Kristina; Thibodeau, Stephen N.; Lindor, Noralane M.; Young, Joanne; Winship, Ingrid; Dowty, James G.; White, Darren M.; Hopper, John L.; Baglietto, Laura; Jenkins, Mark A.; de la Chapelle, Albert

2009-01-01

Background and Aims Although the clinical phenotype of Lynch syndrome (also known as Hereditary Nonpolyposis Colorectal Cancer) has been well described, little is known about disease in PMS2 mutation carriers. Now that mutation detection methods can discern mutations in PMS2 from mutations in its pseudogenes, more mutation carriers have been identified. Information about the clinical significance of PMS2 mutations is crucial for appropriate counseling. Here, we report the clinical characteristics of a large series of PMS2 mutation carriers. Methods We performed PMS2 mutation analysis using long range PCR and MLPA for 99 probands diagnosed with Lynch syndrome-associated tumors showing isolated loss of PMS2 by immunohistochemistry. Penetrance was calculated using a modified segregation analysis adjusting for ascertainment. Results Germline PMS2 mutations were detected in 62% of probands (n = 55 monoallelic; 6 biallelic). Among families with monoallelic PMS2 mutations, 65.5% met revised Bethesda guidelines. Compared with the general population, in mutation carriers, the incidence of colorectal cancer was 5.2 fold higher and the incidence of endometrial cancer was 7.5 fold higher. In North America, this translates to a cumulative cancer risk to age 70 of 15–20% for colorectal cancer, 15% for endometrial cancer, and 25–32% for any Lynch syndrome-associated cancer. No elevated risk for non-Lynch syndrome-associated cancers was observed. Conclusions PMS2 mutations contribute significantly to Lynch syndrome but the penetrance for monoallelic mutation carriers appears to be lower than that for the other mismatch repair genes. Modified counseling and cancer surveillance guidelines for PMS2 mutation carriers are proposed. PMID:18602922

Strategies to Identify the Lynch Syndrome Among Patients With Colorectal Cancer

Science.gov (United States)

Ladabaum, Uri; Wang, Grace; Terdiman, Jonathan; Blanco, Amie; Kuppermann, Miriam; Boland, C. Richard; Ford, James; Elkin, Elena; Phillips, Kathryn A.

2013-01-01

Background Testing has been advocated for all persons with newly diagnosed colorectal cancer to identify families with the Lynch syndrome, an autosomal dominant cancer-predisposition syndrome that is a paradigm for personalized medicine. Objective To estimate the effectiveness and cost-effectiveness of strategies to identify the Lynch syndrome, with attention to sex, age at screening, and differential effects for probands and relatives. Design Markov model that incorporated risk for colorectal, endometrial, and ovarian cancers. Data Sources Published literature. Target Population All persons with newly diagnosed colorectal cancer and their relatives. Time Horizon Lifetime. Perspective Third-party payer. Intervention Strategies based on clinical criteria, prediction algorithms, tumor testing, or up-front germline mutation testing, followed by tailored screening and risk-reducing surgery. Outcome Measures Life-years, cancer cases and deaths, costs, and incremental cost-effectiveness ratios. Results of Base-Case Analysis The benefit of all strategies accrued primarily to relatives with a mutation associated with the Lynch syndrome, particularly women, whose life expectancy could increase by approximately 4 years with hysterectomy and salpingo-oophorectomy and adherence to colorectal cancer screening recommendations. At current rates of germline testing, screening, and prophylactic surgery, the strategies reduced deaths from colorectal cancer by 7% to 42% and deaths from endometrial and ovarian cancer by 1% to 6%. Among tumor-testing strategies, immunohistochemistry followed by BRAF mutation testing was preferred, with an incremental cost-effectiveness ratio of $36 200 per life-year gained. Results of Sensitivity Analysis The number of relatives tested per proband was a critical determinant of both effectiveness and cost-effectiveness, with testing of 3 to 4 relatives required for most strategies to meet a threshold of $50 000 per life-year gained. Immunohistochemistry

Mike Lynch

DEFF Research Database (Denmark)

Horst, Maja; Irwin, Alan

associated with this position and especially its relationship to STS traditions of policy relevance and engagement. What does it mean for STS to do its job? Or rather, what does it mean for us to do our jobs? Taking inspiration both from Lynch’s published work and the different ways he has performed his STS...... jobs, this presentation will discuss the relationship between vacation, work, professional ethos and personal contribution in the context of STS.......In ’Science as a vacation’, Michael Lynch argues that ’STS might aim for something other than the serious job of doing business’. In so doing, he makes a strong case for an STS that does not aim to be useful but instead does ‘its own job’. In our presentation, we will explore some of the challenges...

A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients.

Science.gov (United States)

Snowsill, Tristan; Huxley, Nicola; Hoyle, Martin; Jones-Hughes, Tracey; Coelho, Helen; Cooper, Chris; Frayling, Ian; Hyde, Chris

2015-04-25

Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost-utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could outweigh

Gain of chromosomal region 20q and loss of 18 discriminates between Lynch syndrome and familial colorectal cancer

DEFF Research Database (Denmark)

Therkildsen, Christina; Jönsson, Göran; Dominguez-Valentin, Mev

2013-01-01

Lynch syndrome and familial colorectal cancer type X, FCCTX, represent the two predominant colorectal cancer syndromes. Whereas Lynch syndrome is clinically and genetically well defined, the genetic cause of FCCTX is unknown and genomic differences between Lynch syndrome and FCCTX tumours...... are largely unknown. We applied array-based comparative genomic hybridisation to 23 colorectal cancers from FCCTX with comparison to 23 Lynch syndrome tumours and to 45 sporadic colorectal cancers. FCCTX tumours showed genomic complexity with frequent gains on chromosomes 20q, 19 and 17 and losses of 18, 8p...... and 15. Gain of genetic material in two separate regions encompassing, 20q12-13.12 and 20q13.2-13.32, was identified in 65% of the FCCTX tumours. Gain of material on chromosome 20q and loss on chromosome 18 significantly discriminated colorectal cancers associated with FCCTX from Lynch syndrome, which...

The mutational spectrum of Lynch syndrome in cyprus.

Directory of Open Access Journals (Sweden)

Maria A Loizidou

Full Text Available Lynch syndrome is the most common form of hereditary colorectal cancer and is caused by germline mutations in the mismatch repair (MMR genes MLH1, MSH2, MSH6 and PMS2. Mutation carriers have an increased lifetime risk of developing colorectal cancer as well as other extracolonic tumours. The aim of the current study was to evaluate the frequency and distribution of mutations in the MLH1, MSH2 and MSH6 genes within a cohort of Cypriot families that fulfilled the revised Bethesda guidelines. The study cohort included 77 patients who fulfilled at least one of the revised Bethesda guidelines. Mutational analysis revealed the presence of 4 pathogenic mutations, 3 in the MLH1 gene and 1 in the MSH2 gene, in 5 unrelated individuals. It is noted that out of the 4 pathogenic mutations detected, one is novel (c.1610delG in exon 14 of the MLH1 and has been detected for the first time in the Cypriot population. Overall, the pathogenic mutation detection rate in our patient cohort was 7%. This percentage is relatively low but could be explained by the fact that the sole criterion for genetic screening was compliance to the revised Bethesda guidelines. Larger numbers of Lynch syndrome families and screening of the two additional predisposition genes, PMS2 and EPCAM, are needed in order to decipher the full spectrum of mutations associated with Lynch syndrome predisposition in Cyprus.

Common mutations identified in the MLH1 gene in familial Lynch syndrome

OpenAIRE

Jisha Elias; Coral Karunakaran; Snigdha Majumder; Malini Manoharan; Rakshit Shah; Yogesh Mistry; Rajesh Ramanuj; Niraj Bhatt; Arati Khanna- Gupta

2017-01-01

Lynch syndrome (Hereditary Non Polyposis Colorectal Cancer, HNPCC) is one of the most common hereditary familial colorectal cancers (CRC) with an autosomal dominant pattern of inheritance. It accounts for 2-5% of the total CRCs reported worldwide. Although a lower incidence for CRCs have been observed in India, the last decade has shown a remarkable increase of CRC incidences (2-4 %). Features of Lynch syndrome associated colorectal cancer include early age of cancer onset, accelerated car...

General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: findings from a national survey.

Science.gov (United States)

Smith, Samuel G; Foy, Robbie; McGowan, Jennifer; Kobayashi, Lindsay C; Burn, John; Brown, Karen; Side, Lucy; Cuzick, Jack

2017-10-01

A dose non-inferiority study comparing 100 mg, 300 mg and 600 mg of aspirin for cancer prevention among Lynch Syndrome carriers is underway (Colorectal Adenoma/Carcinoma Prevention Programme trial 3, CaPP3). To guide implementation of the findings, we investigated general practitioner (GP) attitudes towards aspirin prescribing for Lynch Syndrome carriers. We surveyed 1007 UK GPs (9.6% response rate). Using a within-subjects design, GPs read a statement on harms and benefits of aspirin and indicated their willingness to prescribe aspirin at three doses (100 mg, 300 mg, 600 mg). Approximately two-thirds (70.8%) of GPs had heard of Lynch Syndrome or its associated names, and among those 46.7% were aware of the cancer preventive effects of aspirin among carriers. Two-thirds (68.1%) of GPs reported feeling comfortable discussing harms and benefits of aspirin with a Lynch Syndrome patient. Willingness to prescribe was 91.3% at 100 mg, and declined to 81.8% at 300 mg and 62.3% at 600 mg (p Lynch Syndrome patient in practice (OR 1.44, 95% CI 1.01-2.05, p = 0.045). GPs report limited awareness of Lynch Syndrome and the preventive effects of aspirin among carriers. To ensure the optimal dose identified in the CaPP3 trial is readily available to patients, prescribing guidance and strategies to educate GPs should be developed.

Ssk or Esw? -- the Bloor-Lynch Debate Revisited

Science.gov (United States)

Cheng, Kai-Yuan

2014-03-01

Philosophical discussions of rule-following in the later Wittgenstein (1953, 1967) are an important source of inspiration for the development of views on the social nature of scientific knowledge. Two major opposing views in this inquiry -- Bloor's sociology of scientific knowledge (SSK) (1983, 1991, 1992, 1997) and Lynch's (1992, 1993) ethnomethodological studies of work (ESW) -- represent two positions derived from two different readings of Wittgenstein's later writings on rule-following. The aim of this paper is two-fold. One is to re-examine the noted Bloor-Lynch debate by considering Kusch's (2004) recent discussion of this debate. Another is to show that a new semantic framework of rule-following ascriptions based on a cognitive approach to the study of generics can be provided such that SSK and ESW are compatible in it (Leslie, 2009; Cheng, 2011).

Limited impact on self-concept in individuals with Lynch syndrome; results from a national cohort study

DEFF Research Database (Denmark)

Petersen, Helle Vendel; Esplen, Mary Jane; Ladelund, Steen

2011-01-01

An increasing number of individuals seek genetic counseling and hereby learn about hereditary cancer in the family. Lynch syndrome is associated with an inherited high risk for colorectal and gynecological cancer, but knowledge about how family members at risk perceive their situation is limited....... We used the national Danish HNPCC register to collect data on self-concept from 413 individuals with Lynch syndrome. The recently developed Lynch syndrome self-concept scale contains 20 items within two subscales related to stigma-vulnerability and bowel symptom-related anxiety. Significantly higher...... more often reported by women (odds ratio 1.8) and by individuals with less education (OR 1.8). This study provides the first extended use of the Lynch syndrome self-concept scale and suggests that the majority of the Danish mutation carriers adapt well to the situation, though knowledge about...

Indsigter og udfordringer i danske Lynch-syndrom-familier

DEFF Research Database (Denmark)

Therkildsen, Christina; Timshel, Susanne; Nilbert, Mef

2008-01-01

identified 88 unique mutations in 164 Danish families delineated as Lynch syndrome families. Predictive genetic diagnostics enables the identification of high risk individuals, who are offered participation in surveillance programmes that effectively reduce morbidity and mortality in colorectal cancer....

Characterization of Anopheles gambiae s.l. and insecticide ...

African Journals Online (AJOL)

Malaria is endemic in Ghana as in most countries of sub-Saharan Africa. This study was conducted to characterize Anopheles gambiae s.l. and determine pyrethroid resistance profiles relative to physicochemical properties of breeding habitats in Accra, Ghana. Eight aquatic habitats containing Anopheles larvae were ...

Household-level and surrounding peri-domestic environmental characteristics associated with malaria vectors Anopheles arabiensis and Anopheles funestus along an urban-rural continuum in Blantyre, Malawi.

Science.gov (United States)

Dear, Nicole F; Kadangwe, Chifundo; Mzilahowa, Themba; Bauleni, Andy; Mathanga, Don P; Duster, Chifundo; Walker, Edward D; Wilson, Mark L

2018-06-08

Malaria is increasing in some recently urbanized areas that historically were considered lower risk. Understanding what drives urban transmission is hampered by inconsistencies in how "urban" contexts are defined. A dichotomized "urban-rural" approach, based on political boundaries may misclassify environments or fail to capture local drivers of risk. Small-scale agriculture in urban or peri-urban settings has been shown to be a major risk determinant. Household-level Anopheles abundance patterns in and around Malawi's commercial capital of Blantyre (~ 1.9 M pop.) were analysed. Clusters (N = 64) of five houses each located at 2.5 km intervals along eight transects radiating out from Blantyre city centre were sampled during rainy and dry seasons of 2015 and 2016. Mosquito densities were measured inside houses using aspirators to sample resting mosquitoes, and un-baited CDC light traps to sample host seeking mosquitoes. Of 38,895 mosquitoes captured, 91% were female and 87% were Culex spp. Anopheles females (N = 5058) were primarily captured in light traps (97%). Anopheles abundance was greater during rainy seasons. Anopheles funestus was more abundant than Anopheles arabiensis, but both were found on all transects, and had similar associations with environmental risk factors. Anopheles funestus and An. arabiensis females significantly increased with distance from the urban centre, but this trend was not consistent across all transects. Presence of small-scale agriculture was predictive of greater Anopheles spp. abundance, even after controlling for urbanicity, number of nets per person, number of under-5-year olds, years of education, and season. This study revealed how small-scale agriculture along a rural-to-urban transition was associated with An. arabiensis and An. funestus indoor abundances, and that indoor Anopheles density can be high within Blantyre city limits, particularly where agriculture is present. Typical rural areas with lower house

A model-based assessment of the cost–utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients

International Nuclear Information System (INIS)

Snowsill, Tristan; Huxley, Nicola; Hoyle, Martin; Jones-Hughes, Tracey; Coelho, Helen; Cooper, Chris; Frayling, Ian; Hyde, Chris

2015-01-01

Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost–utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could

Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome : a cohort study

NARCIS (Netherlands)

Kempers, Marlies J. E.; Kuiper, Roland P.; Ockeloen, Charlotte W.; Chappuis, Pierre O.; Hutter, Pierre; Rahner, Nils; Schackert, Hans K.; Steinke, Verena; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Buettner, Reinhard; Verwiel, Eugene T. P.; van Krieken, J. Han; Nagtegaal, Iris D.; Goossens, Monique; van der Post, Rachel S.; Niessen, Renee C.; Sijmons, Rolf H.; Kluijt, Irma; Hogervorst, Frans B. L.; Leter, Edward M.; Gille, Johan J. P.; Aalfs, Cora M.; Redeker, Egbert J. W.; Hes, Frederik J.; Tops, Carli M. J.; van Nesselrooij, Bernadette P. M.; van Gijn, Marielle E.; Garcia, Encarna B. Gomez; Eccles, Diana M.; Bunyan, David J.; Syngal, Sapna; Stoffel, Elena M.; Culver, Julie O.; Palomares, Melanie R.; Graham, Tracy; Velsher, Lea; Papp, Janos; Olah, Edith; Chan, Tsun L.; Leung, Suet Y.; van Kessel, Ad Geurts; Kiemeney, Lambertus A. L. M.; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J. L.

Background Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of

Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

Science.gov (United States)

Yurgelun, Matthew B; Allen, Brian; Kaldate, Rajesh R; Bowles, Karla R; Judkins, Thaddeus; Kaushik, Praveen; Roa, Benjamin B; Wenstrup, Richard J; Hartman, Anne-Renee; Syngal, Sapna

2015-09-01

Multigene panels are commercially available tools for hereditary cancer risk assessment that allow for next-generation sequencing of numerous genes in parallel. However, it is not clear if these panels offer advantages over traditional genetic testing. We investigated the number of cancer predisposition gene mutations identified by parallel sequencing in individuals with suspected Lynch syndrome. We performed germline analysis with a 25-gene, next-generation sequencing panel using DNA from 1260 individuals who underwent clinical genetic testing for Lynch syndrome from 2012 through 2013. All patients had a history of Lynch syndrome-associated cancer and/or polyps. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations and variants of uncertain clinical significance (VUS). We also analyzed data on patients' personal and family history of cancer, including fulfillment of clinical guidelines for genetic testing. Of the 1260 patients, 1112 met National Comprehensive Cancer Network (NCCN) criteria for Lynch syndrome testing (88%; 95% confidence interval [CI], 86%-90%). Multigene panel testing identified 114 probands with Lynch syndrome mutations (9.0%; 95% CI, 7.6%-10.8%) and 71 with mutations in other cancer predisposition genes (5.6%; 95% CI, 4.4%-7.1%). Fifteen individuals had mutations in BRCA1 or BRCA2; 93% of these met the NCCN criteria for Lynch syndrome testing and 33% met NCCN criteria for BRCA1 and BRCA2 analysis (P = .0017). An additional 9 individuals carried mutations in other genes linked to high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria for Lynch syndrome testing. A total of 479 individuals had 1 or more VUS (38%; 95% CI, 35%-41%). In individuals with suspected Lynch syndrome, multigene panel testing identified high-penetrance mutations in cancer predisposition genes, many

Identification of MSH2 inversion of exons 1-7 in clinical evaluation of families with suspected Lynch syndrome.

Science.gov (United States)

Mork, Maureen E; Rodriguez, Andrea; Taggart, Melissa W; Rodriguez-Bigas, Miguel A; Lynch, Patrick M; Bannon, Sarah A; You, Y Nancy; Vilar, Eduardo

2017-07-01

Traditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion of MSH2 exons 1-7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Four probands whose Lynch syndrome-associated tumors demonstrated absence of MSH2/MSH6 staining and who had negative MMR germline testing were evaluated for the MSH2 inversion of exons 1-7, offered during initial genetic workup or upon routine clinical follow-up. All four probands tested positive for the MSH2 inversion. Proband cancer diagnoses included colon and endometrial adenocarcinoma and sebaceous adenoma. A variety of Lynch syndrome-associated cancers were reported in the family histories, although only one family met Amsterdam II criteria. Thirteen at-risk relatives underwent predictive testing. MSH2 inversion of exons 1-7 was found in four probands previously suspected to have Lynch syndrome based on family history and tumor testing. This testing should be offered routinely to patients with tumors demonstrating loss of MSH2/MSH6 staining.

The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.

Science.gov (United States)

Senter, Leigha; Clendenning, Mark; Sotamaa, Kaisa; Hampel, Heather; Green, Jane; Potter, John D; Lindblom, Annika; Lagerstedt, Kristina; Thibodeau, Stephen N; Lindor, Noralane M; Young, Joanne; Winship, Ingrid; Dowty, James G; White, Darren M; Hopper, John L; Baglietto, Laura; Jenkins, Mark A; de la Chapelle, Albert

2008-08-01

Although the clinical phenotype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer) has been well described, little is known about disease in PMS2 mutation carriers. Now that mutation detection methods can discern mutations in PMS2 from mutations in its pseudogenes, more mutation carriers have been identified. Information about the clinical significance of PMS2 mutations is crucial for appropriate counseling. Here, we report the clinical characteristics of a large series of PMS2 mutation carriers. We performed PMS2 mutation analysis using long-range polymerase chain reaction and multiplex ligation-dependent probe amplification for 99 probands diagnosed with Lynch syndrome-associated tumors showing isolated loss of PMS2 by immunohistochemistry. Penetrance was calculated using a modified segregation analysis adjusting for ascertainment. Germ-line PMS2 mutations were detected in 62% of probands (n = 55 monoallelic; 6 biallelic). Among families with monoallelic PMS2 mutations, 65.5% met revised Bethesda guidelines. Compared with the general population, in mutation carriers, the incidence of colorectal cancer was 5.2-fold higher, and the incidence of endometrial cancer was 7.5-fold higher. In North America, this translates to a cumulative cancer risk to age 70 years of 15%-20% for colorectal cancer, 15% for endometrial cancer, and 25%-32% for any Lynch syndrome-associated cancer. No elevated risk for non-Lynch syndrome-associated cancers was observed. PMS2 mutations contribute significantly to Lynch syndrome, but the penetrance for monoallelic mutation carriers appears to be lower than that for the other mismatch repair genes. Modified counseling and cancer surveillance guidelines for PMS2 mutation carriers are proposed.

A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome

DEFF Research Database (Denmark)

Clendenning, Mark; Senter, Leigha; Hampel, Heather

2008-01-01

BACKGROUND: When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within PMS2 has been limited (Lynch syndrome cases...... on immunohistochemical analysis. RESULTS: We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n=61). These individuals all display the rare allele (population...... are caused by PMS2. This disparity is primarily due to complications in the study of this gene caused by interference from pseudogene sequences. METHODS: Using a recently developed method for detecting PMS2 specific mutations, we have screened 99 patients who are likely candidates for PMS2 mutations based...

Role of new endoscopic techniques in Lynch syndrome

NARCIS (Netherlands)

Haanstra, Jasmijn F.; Kleibeuker, Jan H.; Koornstra, Jan J.

Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is the most common hereditary condition predisposing for colorectal cancer. International guidelines recommend surveillance of the colorectum by colonoscopy every 1-2 years starting at the age of 20-25 years. This has been shown

Lynch Syndrome Caused by Germline PMS2 Mutations

DEFF Research Database (Denmark)

Ten Broeke, Sanne W; Brohet, Richard M; Tops, Carli M

2015-01-01

PURPOSE: The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. METHODS: Data were collected from 98...... PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks....... Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. RESULTS: The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52...

Efektivitas Bacillus thuringiensis dalam Pengendalian Larva Nyamuk Anopheles sp.

Directory of Open Access Journals (Sweden)

Citra Inneke Wibowo

2017-08-01

Full Text Available Nyamuk Anopheles sp adalah vektor penyakit malaria. Pengendalian vektor penyakit malaria dapat dilakukan secara biologis yaitu dengan menggunakan Bacillus thuringiensis. Tujuan penelitian adalah untuk mengetahui efektivitas konsentrasi Bacillus thuringiensis dalam pengendalian larva nyamuk Anopheles sp.Penelitian ini dilakukan secara eksperimental menggunakan Rancangan Acak Lengkap Faktorial (RAL Faktorial yang terdiri atas dua faktor yaitu konsentrasi Bacillus thuringiensis dan stadia larva Anopheles dengan pengulangan tiga kali.Perlakuan yang dicobakan adalahkonsentrasi Bacillus thuringiensis (A yang terdiri atas 5 taraf:A0: konsentrasi B.thuringiensis 0 CFU.mL-1, A1: konsentrasi B.thuringiensis 102 CFU.mL-1, A2: konsentrasi B.thuringiensis 104 CFU.mL-1, A3: konsentrasi B.thuringiensis 106CFU.mL-1, A4: konsentrasi B.thuringiensis 108CFU.mL-1. Perlakuan tahapan instar larva Anopheles sp. (B adalah sebagai berikut:B1: stadia larva instar I, B2: stadia larva instar II, B3: stadia larva instar III, B4: stadia larva instar IVsehingga terdapat 60 satuan percobaan. Hasil penelitian  menunjukkan konsentrasi B. thuringiensis isolat CK dan IPB CC yang paling berpengaruh dalam pengendalian larva Anopheles sp adalah 108 CFU.mL-1 . Instar larva yang paling peka terhadap B. thuringiensis isolat IPB CC adalah instar I dan II sedangkan instar yang peka terhadap isolat CK adalah instar II, Perlakuan konsentrasi isolat B. thuringiensis dan tingkat instar larva yang paling baik dalam pengendalian larva Anopheles sp. adalah 108 CFU.mL-1, dan instar I dan II.

A review of statistical methods for testing genetic anticipation: looking for an answer in Lynch syndrome

DEFF Research Database (Denmark)

Boonstra, Philip S; Gruber, Stephen B; Raymond, Victoria M

2010-01-01

the issue of multiplex ascertainment and its effect on the different methods. We then focus on exploring genetic anticipation in Lynch syndrome and analyze new data on the age of onset in affected parent-child pairs from families seen at the University of Michigan Cancer Genetics clinic with a mutation...... in one of the three main mismatch repair (MMR) genes. In contrast to the clinic-based population, we re-analyze data on a population-based Lynch syndrome cohort, derived from the Danish HNPCC-register. Both datasets indicate evidence of genetic anticipation in Lynch syndrome. We then expand our review...

Microbial Pre-exposure and Vectorial Competence of Anopheles Mosquitoes

Directory of Open Access Journals (Sweden)

Constentin Dieme

2017-12-01

Full Text Available Anopheles female mosquitoes can transmit Plasmodium, the malaria parasite. During their aquatic life, wild Anopheles mosquito larvae are exposed to a huge diversity of microbes present in their breeding sites. Later, adult females often take successive blood meals that might also carry different micro-organisms, including parasites, bacteria, and viruses. Therefore, prior to Plasmodium ingestion, the mosquito biology could be modulated at different life stages by a suite of microbes present in larval breeding sites, as well as in the adult environment. In this article, we highlight several naturally relevant scenarios of Anopheles microbial pre-exposure that we assume might impact mosquito vectorial competence for the malaria parasite: (i larval microbial exposures; (ii protist co-infections; (iii virus co-infections; and (iv pathogenic bacteria co-infections. In addition, significant behavioral changes in African Anopheles vectors have been associated with increasing insecticide resistance. We discuss how these ethological modifications may also increase the repertoire of microbes to which mosquitoes could be exposed, and that might also influence their vectorial competence. Studying Plasmodium–Anopheles interactions in natural microbial environments would efficiently contribute to refining the transmission risks.

Using Social Media Data to Understand the Impact of Promotional Information on Laypeople's Discussions: A Case Study of Lynch Syndrome.

Science.gov (United States)

Bian, Jiang; Zhao, Yunpeng; Salloum, Ramzi G; Guo, Yi; Wang, Mo; Prosperi, Mattia; Zhang, Hansi; Du, Xinsong; Ramirez-Diaz, Laura J; He, Zhe; Sun, Yuan

2017-12-13

Social media is being used by various stakeholders among pharmaceutical companies, government agencies, health care organizations, professionals, and news media as a way of engaging audiences to raise disease awareness and ultimately to improve public health. Nevertheless, it is unclear what effects this health information has on laypeople. This study aimed to provide a detailed examination of how promotional health information related to Lynch syndrome impacts laypeople's discussions on a social media platform (Twitter) in terms of topic awareness and attitudes. We used topic modeling and sentiment analysis techniques on Lynch syndrome-related tweets to answer the following research questions (RQs): (1) what are the most discussed topics in Lynch syndrome-related tweets?; (2) how promotional Lynch syndrome-related information on Twitter affects laypeople's discussions?; and (3) what impact do the Lynch syndrome awareness activities in the Colon Cancer Awareness Month and Lynch Syndrome Awareness Day have on laypeople's discussions and their attitudes? In particular, we used a set of keywords to collect Lynch syndrome-related tweets from October 26, 2016 to August 11, 2017 (289 days) through the Twitter public search application programming interface (API). We experimented with two different classification methods to categorize tweets into the following three classes: (1) irrelevant, (2) promotional health information, and (3) laypeople's discussions. We applied a topic modeling method to discover the themes in these Lynch syndrome-related tweets and conducted sentiment analysis on each layperson's tweet to gauge the writer's attitude (ie, positive, negative, and neutral) toward Lynch syndrome. The topic modeling and sentiment analysis results were elaborated to answer the three RQs. Of all tweets (N=16,667), 87.38% (14,564/16,667) were related to Lynch syndrome. Of the Lynch syndrome-related tweets, 81.43% (11,860/14,564) were classified as promotional and 18

Capacidad entomocida de cepas nativas de Beauveria sp. sobre Schistocerca piceifrons peruviana (Lynch Arribalzaga, 1903

Directory of Open Access Journals (Sweden)

Nicolaza Pariona

2013-04-01

Full Text Available Cuatro cepas de Beauveria sp. (ABvPr11, ABvPr8, ABvPr3 y ABvSr4, fueron aisladas y caracterizadas de ejemplares de la langosta Schistocerca piceifrons peruviana procedentes de la Provincia de Huamanga del Departamento de Ayacucho. La capacidad entomocida de las 4 cepas fue evaluada en la langosta Schistocerca piceifrons peruviana. Los resultados muestran que todas las cepas, en soluciones de 108 conidias/mL, producen un 100% de mortalidad. El tiempo que se necesitó para eliminar el 100% de las langostas, para las cepas ABvPr11, ABvPr8, ABvSr4 y ABvPr3 fue de 12, 14 y 16 días respectivamente. Al décimo día se observó diferencias significativas respecto a la mortalidad, entre la cepa ABvPr11(90% y la cepas ABvSr4(74%, ABvPr8(72% y ABvPr3(64.6%. Posteriormente se determinó el tiempo de letalidad al 50% (TL50 de la población de langostas, con un intervalo de 8,38 a 9,16 días y el tiempo de letalidad al 80% (TL80 fue de 9,6 a 11,5 días. La cepa ABvPr11 presentó la mayor actividad entomocida para el control de Schistocerca piceifrons peruviana L.A.

Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance : first report from the prospective Lynch syndrome database

NARCIS (Netherlands)

Moller, Pal; Seppala, Toni; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Evans, D. Gareth; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind; Rodland, Einar Andreas; Tharmaratnam, Kukatharmini; Cappel, Wouter H. de Vos Tot Nederveen; Hill, James; Wijnen, Juul; Green, Kate; Lalloo, Fiona; Sunde, Lone; Mints, Miriam; Bertario, Lucio; Pineda, Marta; Navarro, Matilde; Morak, Monika; Renkonen-Sinisalo, Laura; Frayling, Ian M.; Plazzer, John-Paul; Pylvanainen, Kirsi; Sampson, Julian R.; Capella, Gabriel; Mecklin, Jukka-Pekka; Moslein, Gabriela

Objective Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. Design We undertook a multicentre

Using Social Media Data to Understand the Impact of Promotional Information on Laypeople’s Discussions: A Case Study of Lynch Syndrome

Science.gov (United States)

Salloum, Ramzi G; Guo, Yi; Wang, Mo; Prosperi, Mattia; Zhang, Hansi; Du, Xinsong; Ramirez-Diaz, Laura J; He, Zhe

2017-01-01

Background Social media is being used by various stakeholders among pharmaceutical companies, government agencies, health care organizations, professionals, and news media as a way of engaging audiences to raise disease awareness and ultimately to improve public health. Nevertheless, it is unclear what effects this health information has on laypeople. Objective This study aimed to provide a detailed examination of how promotional health information related to Lynch syndrome impacts laypeople’s discussions on a social media platform (Twitter) in terms of topic awareness and attitudes. Methods We used topic modeling and sentiment analysis techniques on Lynch syndrome–related tweets to answer the following research questions (RQs): (1) what are the most discussed topics in Lynch syndrome–related tweets?; (2) how promotional Lynch syndrome–related information on Twitter affects laypeople’s discussions?; and (3) what impact do the Lynch syndrome awareness activities in the Colon Cancer Awareness Month and Lynch Syndrome Awareness Day have on laypeople’s discussions and their attitudes? In particular, we used a set of keywords to collect Lynch syndrome–related tweets from October 26, 2016 to August 11, 2017 (289 days) through the Twitter public search application programming interface (API). We experimented with two different classification methods to categorize tweets into the following three classes: (1) irrelevant, (2) promotional health information, and (3) laypeople’s discussions. We applied a topic modeling method to discover the themes in these Lynch syndrome–related tweets and conducted sentiment analysis on each layperson’s tweet to gauge the writer’s attitude (ie, positive, negative, and neutral) toward Lynch syndrome. The topic modeling and sentiment analysis results were elaborated to answer the three RQs. Results Of all tweets (N=16,667), 87.38% (14,564/16,667) were related to Lynch syndrome. Of the Lynch syndrome–related tweets, 81

Surveillance for urinary tract cancer in Lynch syndrome

DEFF Research Database (Denmark)

Bernstein, Inge Thomsen; Myrhøj, Torben

2013-01-01

Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited multiorgan cancer syndrome, which when caused by a germline mutation in the mismatch repair (MMR) genes is known as Lynch syndrome (LS). Mutation carriers are at risk for developing cancers primarily in the colon, rectum...

Structural divergence of chromosomes between malaria vectors Anopheles lesteri and Anopheles sinensis

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Jiangtao Liang

2016-11-01

Full Text Available Abstract Background Anopheles lesteri and Anopheles sinensis are two major malaria vectors in China and Southeast Asia. They are dramatically different in terms of geographical distribution, host preference, resting habitats, and other traits associated with ecological adaptation and malaria transmission. Both species belong to the Anopheles hyrcanus group, but the extent of genetic differences between them is not well understood. To provide an effective way to differentiate between species and to find useful markers for population genetics studies, we performed a comparative cytogenetic analysis of these two malaria vectors. Results Presented here is a standard cytogenetic map for An. lesteri, and a comparative analysis of chromosome structure and gene order between An. lesteri and An. sinensis. Our results demonstrate that much of the gene order on chromosomes X and 2 was reshuffled between the two species. However, the banding pattern and the gene order on chromosome 3 appeared to be conserved. We also found two new polymorphic inversions, 2Lc and 3Rb, in An. lesteri, and we mapped the breakpoints of these two inversions on polytene chromosomes. Conclusions Our results demonstrate the extent of structural divergence of chromosomes between An. lesteri and An. sinensis, and provide a new taxonomic cytogenetic tool to distinguish between these two species. Polymorphic inversions of An. lesteri could serve as markers for studies of the population structure and ecological adaptations of this major malaria vector.

Distinct Gene Expression Signatures in Lynch Syndrome and Familial Colorectal Cancer Type X

DEFF Research Database (Denmark)

Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas

2013-01-01

Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....

Factors affecting fungus-induced larval mortality in Anopheles gambiae and Anopheles stephensi

NARCIS (Netherlands)

Bukhari, S.T.; Middelman, A.; Koenraadt, C.J.M.; Takken, W.; Knols, B.G.J.

2010-01-01

Background Entomopathogenic fungi have shown great potential for the control of adult malaria vectors. However, their ability to control aquatic stages of anopheline vectors remains largely unexplored. Therefore, how larval characteristics (Anopheles species, age and larval density), fungus (species

Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.

Science.gov (United States)

Wagner, David G; Gatalica, Zoran; Lynch, Henry T; Kohl, Shane; Johansson, Sonny L; Lele, Subodh M

2010-12-01

Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

Resurrection of Anopheles goeldii from synonymy with Anopheles nuneztovari (Diptera, Culicidae and a new record for Anopheles dunhami in the Brazilian Amazon

Directory of Open Access Journals (Sweden)

Daniéla C Calado

2008-12-01

Full Text Available Nucleotide sequences of the internal transcribed spacer 2 (ITS2 rDNA and partial sequences of the cytochrome coxidase subunit I (COI mtDNA and white gene nDNA were obtained from specimens of Anopheles nuneztovari A collected in Macapá (state of Amapá, Óbidos, Prainha and Almeirim (state of Pará, Itacoatiara and Parintins (state of Amazonas, Brazil, and compared with previously published sequences of A. nuneztovari s.l. Results of the Bayesian phylogenetic analyses performed using either COI or combined ITS2, COI and white gene sequences suggest that An. nuneztovari B/C is distinct from specimens obtained in the Amazonas/Solimões River basin. Anopheles goeldii, currently in synonymy with An. nuneztovari, was described from individuals collected in Belterra (= Fordlândia in the Tapajós River, state of Pará, Southern Amazonas River. Morphological comparisons of the characteristics of the male genitalia indicated that An. nuneztovari A and An. goeldii are similar but distinct from An. nuneztovariB/C by the apex of the aedeagus. In considering the results of the phylogenetic analyses and morphological comparisons, An. goeldii is resurrected from synonymy with An. nuneztovari. Additionally, Anopheles dunhamiis reported for the first time in Parintins. This species can be distinguished from An. goeldiiby characters of the male genitalia and molecular data.

Utility of MLH1 methylation analysis in the clinical evaluation of Lynch Syndrome in women with endometrial cancer.

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Bruegl, Amanda S; Djordjevic, Bojana; Urbauer, Diana L; Westin, Shannon N; Soliman, Pamela T; Lu, Karen H; Luthra, Rajyalakshmi; Broaddus, Russell R

2014-01-01

Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.

Lynch syndrome: barriers to and facilitators of screening and disease management.

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Watkins, Kathy E; Way, Christine Y; Fiander, Jacqueline J; Meadus, Robert J; Esplen, Mary Jane; Green, Jane S; Ludlow, Valerie C; Etchegary, Holly A; Parfrey, Patrick S

2011-09-07

Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health.

Lynch syndrome: barriers to and facilitators of screening and disease management

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Watkins Kathy E

2011-09-01

Full Text Available Abstract Background Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. Methods The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23 were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. Results Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. Conclusions Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health.

Same MSH2 Gene Mutation But Variable Phenotypes in 2 Families With Lynch Syndrome: Two Case Reports and Review of Genotype-Phenotype Correlation.

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Liccardo, Raffaella; De Rosa, Marina; Duraturo, Francesca

2018-01-01

Lynch syndrome is an autosomal dominant syndrome that can be subdivided into Lynch syndrome I, or site-specific colonic cancer, and Lynch syndrome II, or extracolonic cancers, particularly carcinomas of the stomach, endometrium, biliary and pancreatic systems, and urinary tract. Lynch syndrome is associated with point mutations and large rearrangements in DNA MisMatch Repair ( MMR ) genes. This syndrome shows a variable phenotypic expression in people who carry pathogenetic mutations. So far, a correlation in genotype-phenotype has not been definitely established. In this study, we describe 2 Lynch syndrome cases presenting with the same genotype but different phenotypes and discuss possible reasons for this.

Diversification of the Genus Anopheles and a Neotropical Clade from the Late Cretaceous.

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Lucas A Freitas

Full Text Available The Anopheles genus is a member of the Culicidae family and consists of approximately 460 recognized species. The genus is composed of 7 subgenera with diverse geographical distributions. Despite its huge medical importance, a consensus has not been reached on the phylogenetic relationships among Anopheles subgenera. We assembled a comprehensive dataset comprising the COI, COII and 5.8S rRNA genes and used maximum likelihood and Bayesian inference to estimate the phylogeny and divergence times of six out of the seven Anopheles subgenera. Our analysis reveals a monophyletic group composed of the three exclusively Neotropical subgenera, Stethomyia, Kerteszia and Nyssorhynchus, which began to diversify in the Late Cretaceous, at approximately 90 Ma. The inferred age of the last common ancestor of the Anopheles genus was ca. 110 Ma. The monophyly of all Anopheles subgenera was supported, although we failed to recover a significant level of statistical support for the monophyly of the Anopheles genus. The ages of the last common ancestors of the Neotropical clade and the Anopheles and Cellia subgenera were inferred to be at the Late Cretaceous (ca. 90 Ma. Our analysis failed to statistically support the monophyly of the Anopheles genus because of an unresolved polytomy between Bironella and A. squamifemur.

Laboratory studies on the olfactory behaviour of Anopheles quadriannulatus

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Pates, H.V.; Takken, W.; Curtis, C.F.

2005-01-01

The host preference of Anopheles quadriannulatus Theobald (Diptera: Culicidae), the zoophilic member of the malaria mosquito complex Anopheles gambiae Giles, was investigated in a dual-choice olfactometer. Naïve female mosquitoes were exposed to CO2, acetone, 1-octen-3-ol, and skin emanations from

Variability and genetic differentiation among Anopheles (Ano. intermedius Chagas, 1908 and Anopheles (Ano. mattogrossensis Lutz & Neiva, 1911 (Diptera: Culicidae from the Brazilian Amazon

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Joselita Maria Mendes dos Santos

2005-10-01

Full Text Available Anopheles (Anopheles intermedius and Anopheles (Ano. mattogrossensis are Brazilian anopheline species belonging to the scarcely studied Anopheles subgenus. Few studies have been done on the genetic differentiation of these species. Both species have been found infected by Plasmodium and are sympatric with other anopheline species from the Nyssorhynchus subgenus. Eighteen enzymatic loci were analyzed in larval specimens of An. intermedius and An. mattogrossensis aiming to estimate the variability and genetic differentiation between these species. An. mattogrossensis population showed higher genetic variability (P = 44.4 and Ho = 0.081 ± 0.031 than that of An. intermedius (P = 33.3 and Ho = 0.048 ± 0.021. Most analyzed loci showed genotypic frequencies according to Hardy-Weinberg equilibrium, except for LAP1 and LAP2 in An. intermedius, and EST1 and PGM loci in An. mattogrossensis. The genetic distance between these species (D = 0.683 was consistent with the inter-specific values reported for Anopheles subgenus. We verified that the polymorphism and heterozygosity percentile values found in both species and compared to those in the literature, showed no relation between the level of isozyme variability and geographical distribution. The low variability found in these two species is probably more related to the niche they occupy than to their geographic distribution.

Genetic screens to identify pathogenic gene variants in the common cancer predisposition Lynch syndrome

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Drost, Mark; Lützen, Anne; van Hees, Sandrine

2013-01-01

In many individuals suspected of the common cancer predisposition Lynch syndrome, variants of unclear significance (VUS), rather than an obviously pathogenic mutations, are identified in one of the DNA mismatch repair (MMR) genes. The uncertainty of whether such VUS inactivate MMR, and therefore...... function. When a residue identified as mutated in an individual suspected of Lynch syndrome is listed as critical in such a reverse diagnosis catalog, there is a high probability that the corresponding human VUS is pathogenic. To investigate the applicability of this approach, we have generated....... Nearly half of these critical residues match with VUS previously identified in individuals suspected of Lynch syndrome. This aids in the assignment of pathogenicity to these human VUS and validates the approach described here as a diagnostic tool. In a wider perspective, this work provides a model...

Worldwide Practice Patterns in Lynch Syndrome Diagnosis and Management, Based on Data From the International Mismatch Repair Consortium.

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Pan, Jennifer Y; Haile, Robert W; Templeton, Allyson; Macrae, Finlay; Qin, FeiFei; Sundaram, Vandana; Ladabaum, Uri

2018-04-24

Families with a history of Lynch syndrome often do not adhere to guidelines for genetic testing and screening. We investigated practice patterns related to Lynch syndrome worldwide, to ascertain potential targets for research and public policy efforts. We collected data from the International Mismatch Repair Consortium (IMRC), which comprises major research and clinical groups engaged in the care of families with Lynch syndrome worldwide. IMRC institutions were invited to complete a questionnaire to characterize diagnoses of Lynch syndrome and management practice patterns. Fifty-five providers, representing 63 of 128 member institutions (49%) in 21 countries, completed the questionnaire. For case finding, 55% of respondents reported participating in routine widespread population tumor testing among persons with newly diagnosed Lynch syndrome-associated cancers, whereas 27% reported relying on clinical criteria with selective tumor and/or germline analyses. Most respondents (64%) reported using multigene panels for germline analysis, and only 28% reported testing tumors for biallelic mutations for cases in which suspected pathogenic mutations were not confirmed by germline analysis. Respondents reported relying on passive dissemination of information to at-risk family members, and there was variation in follow through of genetic testing recommendations. Reported risk management practices varied-nearly all programs (98%) recommended colonoscopy every 1 to 2 years, but only 35% recommended chemoprevention with aspirin. There is widespread heterogeneity in management practices for Lynch syndrome worldwide among IMRC member institutions. This may reflect the rapid pace of emerging technology, regional differences in resources, and the lack of definitive data for many clinical questions. Future efforts should focus on the large numbers of high-risk patients without access to state-of-the-art Lynch syndrome management. Copyright © 2018 AGA Institute. Published by

Thyroid cancer in a patient with Lynch syndrome – case report and literature review

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Fazekas-Lavu M

2017-07-01

Full Text Available Monika Fazekas-Lavu,1 Andrew Parker,2 Allan D Spigelman,3,4 Rodney J Scott,5 Richard J Epstein,6 Michael Jensen,7 Katherine Samaras1,8 1Department of Endocrinology, 2Department of Pathology, St Vincent’s Hospital, Darlinghurst, NSW, Australia; 3Hereditary Cancer Clinic, St Vincent’s Cancer Genetics Service, Darlinghurst, NSW, Australia; 4University of NSW, St Vincent’s Clinical School, Darlinghurst, NSW, Australia; 5Division of Molecular Medicine, Pathology North, John Hunter Hospital and The Hunter Medical Research Institute, Newcastle, NSW, Australia; 6Department of Oncology, 7Department of Oncological Surgery/General Surgery, St Vincent’s Hospital, Darlinghurst, NSW, Australia; 8Diabetes and Metabolism Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia Abstract: Lynch syndrome describes a familial cancer syndrome comprising germline mutations in one of four DNA mismatch repair genes, MLH1, MSH2, MSH6, and PMS2 and is characterized by colorectal, endometrial, and other epithelial malignancies. Thyroid cancer is not usually considered to be part of the constellation of Lynch syndrome cancers nor have Lynch syndrome tumor gene mutations been reported in thyroid malignancies. This study reports a woman with Lynch syndrome (colonic cancer and a DNA mismatch repair mutation in the MSH2 gene with a synchronous papillary thyroid cancer. Six years later, she developed metachronous breast cancer. Metastatic bone disease developed after 3 years, and the disease burden was due to both breast and thyroid diseases. Despite multiple interventions for both metastatic breast and thyroid diseases, the patient’s metastatic burden progressed and she died of leptomeningeal metastatic disease. Two prior case reports suggested thyroid cancer may be an extraintestinal malignancy of the Lynch syndrome cancer group. Hence, this study examined the genetic relationship between the patient’s known Lynch syndrome and her

Differential expression of CK20, β-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X.

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Haraldsson, Stefan; Klarskov, Louise; Nilbert, Mef; Bernstein, Inge; Bonde, Jesper; Holck, Susanne

2017-01-01

Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other than MMR proteins. We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX. Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch syndrome ( p  Lynch syndrome tumors compared with FCCTX tumors ( p  = 0.001, Lynch syndrome with a more sporadic-like profile in the former group and a more distinct profile with frequent MUC6 positivity in the latter group.

The effectiveness of the double B-lynch suture as a modification in the treatment of intractable postpartum haemorrhage.

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Şahin, Hanifi; Soylu Karapınar, Oya; Şahin, Eda Adeviye; Dolapçıoğlu, Kenan; Baloğlu, Ali

2018-03-20

A broader range of more effective compression techniques are needed in the patients who have an intractable postpartum haemorrhage due to uterine atony despite medical treatment and B-Lynch sutures. The aim of this study was to report the outcome of a series of patients with haemorrhage who were managed by double B-Lynch suture. Fourteen patients who were treated in a tertiary hospital between July 2010 and February 2015 were included in the study. The intractable haemorrhage rate was 0.35% over 5 years (14/4000 births). Bleeding was controlled in all the patients with a double B-Lynch suture. The mean age of the patients was 24 ± 3.4 years. The mean estimated blood loss was 1696 ± 272.075 mL, and the mean transfusion rate was 4.2 ± 2.5 units. Pregnancy was observed in five patients at follow up. The double B-Lynch suture seems to be an effective and reliable solution to an intractable postpartum haemorrhage resulting from uterine atony and has no unfavourable impacts on fertility. It should be considered before the use of any aggressive surgical techniques such as a hypogastric artery ligation or a hysterectomy. This the first study to investigate the effectiveness of the double B-Lynch suture, and we showed that the hysterectomy and/or hypogastric artery ligation rate can be decreased by adding a second B-Lynch suture in cases where the medical treatment or a single B-Lynch has failed. Impact statement What is already known on the subject? Uterine atony is the most common cause of a primary postpartum haemorrhage. When a simple massage of the uterus and medication failed to manage this condition, various surgical solutions have been sought, including uterine compression sutures, uterine artery ligation, devascularisation of the uterus, internal iliac artery ligation and, ultimately, a hysterectomy. The B-Lynch suturing technique is particularly useful because of its simplicity of application, life-saving potential, relative safety and capacity

BEBERAPA ASPEK PERILAKU NYAMUK Anopheles barbirostris DI KABUPATEN SUMBA TENGAH TAHUN 2011

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Monika Noshirma

2013-02-01

Full Text Available Abstract Some aspects of Anopheles barbirostris behavior in Central Sumba Regency was conducted in July– October in District Umbu Ratu Nggai (Village Padira Tana which represents in mountain ecology and the district of Mamboro (Manu Wollu Village representing the coastal ecology. Both villages are selected to have high malaria cases during the past year. The objective of the study is to determine Some aspect of Anopheles barbirostris behavior in Central Sumba Regency. The result showed that the characteristics of  breeding habitats of Anopheles barbirostris in the padira tana village is in fields (both in use, not use or ready for planting and in kobakan. in Manu Wolu Village the breeding habitats are in former ponds, puddles an kobakan. The bitting activity of Anopheles barbirostris the in Padira Tana Village highest in July (MBR = 0.08 outside the house,  while in Manu Wolu Village bite out of the house in July and October (MBR = 0.04. in the Padira Tana Village and Manu Wollu village the Anopheles barbirostris is most prevalent in the cage with peak hours 11.00 pm to 04.00 am. Keyword: some aspect of vector behavior, Anopheles barbirostris Abstrak Studi beberapa aspek perilaku vektor malaria Anopheles barbirostris di Kabupaten Sumba Tengah dilaksanakan pada bulan Juli – Oktober di 2 Kecamatan yaitu Kecamatan Umbu Ratu (Desa Padira Tana yang mewakili ekologi pegunungan dan Kecamatan Mamboro (Desa Manu Wolu yang mewakili ekologi pantai. Kedua desa yang dipilih mempunyai kasus malaria tinggi selama satu tahun terakhir. Tujuan penelitian ini untuk mengetahui beberapa aspek perilaku vektor Anopheles barbirostris di Kabupaten Sumba Tengah. Hasil penelitian menunjukan bahwa karakteristik habitat perkembangbiakan Anopheles barbirostris di desa Padira Tana adalah sawah (baik yang terpakai, tidak dipakai maupun siap tanam dan di kobakan. Sedangkan di desa Manu Wolu ditemukan di bekas kolam, kubangan dan kobakan.    Kepadatan nyamuk An

Sense of coherence and self-concept in Lynch syndrome

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Petersen, Helle Vendel; Ladelund, Steen; Carlsson, Christina

2013-01-01

Most individuals who learn about hereditary cancer manage well, but identification of subgroups who find this knowledge burdening would allow psychosocial intervention. The objective of the study was to assess sense of coherence (SOC) in individuals with Lynch syndrome with comparison to a general...

Fas Ligand Expression in Lynch Syndrome-Associated Colorectal Tumours

NARCIS (Netherlands)

Koornstra, Jan J.; de Jong, Steven; Boersma-van Eck, Wietske; Zwart, Nynke; Hollema, Harry; de Vries, Elisabeth G. E.; Kleibeuker, Jan H.

Fas Ligand (FasL) expression by cancer cells may contribute to tumour immune escape via the Fas counterattack against tumour-infiltrating lymphocytes (TILs). Whether this plays a role in colorectal carcinogenesis in Lynch syndrome was examined studying FasL expression, tumour cell apoptosis and

SEASONAL DISTRIBUTION OF MALARIA VECTORS (DIPTERA: CULICIDAE IN RURAL LOCALITIES OF PORTO VELHO, RONDÔNIA, BRAZILIAN AMAZON

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Luiz Herman Soares GIL

2015-06-01

Full Text Available We conducted a survey of the malaria vectors in an area where a power line had been constructed, between the municipalities of Porto Velho and Rio Branco, in the states of Rondônia and Acre, respectively. The present paper relates to the results of the survey of Anopheles fauna conducted in the state of Rondônia. Mosquito field collections were performed in six villages along the federal highway BR 364 in the municipality of Porto Velho, namely Porto Velho, Jaci Paraná, Mutum Paraná, Vila Abunã, Vista Alegre do Abunã, and Extrema. Mosquito captures were performed at three distinct sites in each locality during the months of February, July, and October 2011 using a protected human-landing catch method; outdoor and indoor captures were conducted simultaneously at each site for six hours. In the six sampled areas, we captured 2,185 mosquitoes belonging to seven Anopheles species. Of these specimens, 95.1% consisted of Anopheles darlingi, 1.8% An. triannulatus l.s., 1.7% An. deaneorum, 0.8% An. konderi l.s., 0.4 An. braziliensis, 0.1% An. albitarsis l.s., and 0.1% An. benarrochi. An. darlingi was the only species found in all localities; the remaining species occurred in sites with specific characteristics.

LYNCHING IN RUSSIAN COUNTRYSIDE (late XIX-early XX

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Vladimir Borisovich Bezgin

2013-08-01

Full Text Available Research actuality is due to the frequent attempts of extrajudicial killings of criminals in the country as a result of the citizens' law enforcement distrust, their doubt of deserved retribution.Such phenomenon of legal life of the Russian countryside as a lynch mob is studied in the article on the basis of a wide range of archival and ethnographic sources. The author analyzes the crimes for which the perpetrators are arbitrarily subjected to massacre in the village. The role of the peasant community in the punishment implementation of criminals was found out. The causes of the stability of this tradition in rural society were set.Lynching played an effective means of suppression of unlawful acts of the peasants. The collective nature of the spontaneously created killings of criminals was the result of mutual responsibility of community members and rural solidarity preservation condition. According to farmers gathering verdict gave legal force to massacre and left no doubt about the justice of the decision.DOI: http://dx.doi.org/10.12731/2218-7405-2013-8-1

Universal tumor screening for Lynch syndrome: Assessment of the perspectives of patients with colorectal cancer regarding benefits and barriers.

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Hunter, Jessica Ezzell; Zepp, Jamilyn M; Gilmore, Mari J; Davis, James V; Esterberg, Elizabeth J; Muessig, Kristin R; Peterson, Susan K; Syngal, Sapna; Acheson, Louise S; Wiesner, Georgia L; Reiss, Jacob A; Goddard, Katrina A B

2015-09-15

Universal tumor screening for Lynch syndrome, the most common form of hereditary colorectal cancer (CRC), has been recommended among all patients newly diagnosed with CRC. However, there is limited literature regarding patient perspectives of tumor screening for Lynch syndrome among patients with CRC who are not selected for screening based on family history criteria. A total of 145 patients aged 39 to 87 years were administered surveys assessing perceived risk, patient perspectives, and potential benefits of and barriers to tumor screening for Lynch syndrome. Associations between patient-specific and cancer-specific factors and survey responses were analyzed. The majority of participants perceived their risk of developing Lynch syndrome as being low, with 9 participants (6.2%) anticipating an abnormal screening result. However, most participants endorsed the potential benefits of screening for themselves and their families, with 84.8% endorsing ≥6 benefits and 50.3% endorsing all 8 benefits. Participants also endorsed few potential barriers to screening, with 89.4% endorsing ≤4 of 9 potential barriers. A common barrier was worry about the cost of additional testing and surveillance, which was endorsed by 54.5% of participants. The level of distress associated with tumor screening for Lynch syndrome, which was very low, was not associated with age or CRC stage. The results of the current study indicate that patients with CRC overall have a positive attitude toward tumor screening for Lynch syndrome, endorse the benefits of screening, and experience low levels of distress. These findings provide insight into patient attitudes toward tumor screening for Lynch syndrome among unselected patients with CRC to inform educational approaches that assist in patient decision-making and guide the successful implementation of screening programs. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Sebaran Nyamuk Anopheles pada Topografi Wilayah yang Berbeda di Provinsi Jambi

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Yulian Taviv

2015-09-01

Full Text Available Penularan penyakit tular vektor seperti malaria dipengaruhi oleh banyak faktor. Salah satu faktor yangtelah diketahui memiliki asosiasi dengan malaria adalah topograf wilayah yang erat hubungannya denganpola penularan. Berdasarkan tempat atau lokasi terhadap penyakit yang ditularkan oleh vektor makaperlu diperhatikan pembagian zoogeografi dimana jenis-jenis nyamuk di setiap lokasi akan dipengaruhifaktor-faktor lingkungan di setiap daerah yang berbeda. Penelitian ini bertujuan untuk mengetahui jenisAnopheles serta habitat perkembangbiakannya pada dua wilayah dengan topograf yang berbeda diProvinsi Jambi. Kegiatan yang dilakukan adalah penangkapan nyamuk dewasa dengan metode humanlanding collection dan survei habitat perkembangbiakan Anopheles. Penangkapan nyamuk dilakukanselama 12 jam dimulai dari jam 18.00 WIB hingga jam 06.00 WIB. Larva Anopheles yang berhasilditangkap selanjutnya dibawa ke laboratorium dan dipelihara hingga dewasa dan selanjutnya diidentifiasijenisnya. Hasil penangkapan nyamuk Anopheles di Desa Nipah Panjang Kabupaten Tanjung JabungTimur (dataran rendah adalah An. separatus, An. sinensis, An. tesselatus dan An. letifer. Anophelesletifer memiliki angka tertinggi untuk nilai kekerapan 3,33, kelimpahan nisbi 40, dominansi 133,33 danMan Bitting Rate (MBR 0,07. Penangkapan nyamuk Anopheles di Desa Teluk Rendak KabupatenSarolangun (dataran tinggi meliputi An. nigerrimus, An. annularis, An. letifer, An. maculatus dan An.barbumbrosus. Anopheles nigerrimus memiliki angka tertinggi untuk nilai kekerapan 21,67, kelimpahannisbi 60,98, dominansi 1321,14 dan MBR 0,63.

The resting sites and blood-meal sources of Anopheles minimus in Taiwan.

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Chang, Mei-Chun; Teng, Hwa-Jen; Chen, Chen-Fu; Chen, Yung-Chen; Jeng, Chian-Ren

2008-06-09

The WHO declared Taiwan free from malaria in 1965, but in 2003 the reporting of two introduced cases in a rural area suggested a possible local transmission of this disease. Therefore, understanding the resting sites and the blood sources of Anopheles minimus is crucial in order to provide information for implementing vector control strategies. During a two-year survey, mosquitoes were collected in houses and their surrounding areas and at the bank of larval habitats by backpack aspirators in 17 villages in rural areas of southern and eastern Taiwan for 1 hr. On the same day, blacklight traps were hung downward overnight. Blood-fed mosquito samples were analysed by PCR. Of the 195 total households surveyed by backpack aspirators, no Anopheles adults were collected inside the houses, while a single Anopheles minimus and a single Anopheles maculatus were collected outside of the houses. On the same day, 23 An. minimus, two An. maculatus, two Anopheles ludlowae, two Anopheles sinensis, and one Anopheles tessellatus were collected along the bank of larval habitats. In blacklight traps hung outside of the houses in the villages, 69 An. minimus, 62 An. ludlowae, 31 An. sinensis, and 19 An. maculatus were collected. In larval habitats, 98 An. ludlowae, 64 An. minimus, 49 An. sinensis, and 14 An. maculatus were collected. Of a total of 10 blood-fed samples, An. minimus fed on four animals including bovine (60%), dogs (20%), pig (10%), and non-chicken avian (10%). Anopheles minimus, an opportunist feeder in Taiwan, was not collected inside the houses, but was found outside of the houses in villages and surrounding larval habitats. Therefore, an outdoor transmission of malaria is likely to occur and, thus, the bed nets, which are favoured for controlling the late biting of An. minimus, should be a very efficient and effective method for those local residents who sleep outdoors. Additionally, space spray of insecticides for Anopheles at night, as well as residual spray inside

Laboratory Assays in Evaluation of Lynch Syndrome in Patients with Endometrial Carcinoma.

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Djordjevic, Bojana; Broaddus, Russell R

2016-06-01

This article reviews the main tissue testing modalities for Lynch Syndrome in the pathology laboratory, such as immunohistochemistry and PCR based analyses, and discusses their routine application, interpretation pitfalls, and troubleshooting of common technical performance issues. Discrepancies between laboratory and genetic testing may arise, and are examined in the context of the complexity of molecular abnormalities associated with Lynch Syndrome. The merits of targeted versus universal screening in a changing healthcare climate are addressed. In the absence of comprehensive screening programs, specific tumor topography and histological features that may prompt pathologist-initiated molecular tumor testing are outlined. Copyright © 2016 Elsevier Inc. All rights reserved.

Ecology of Anopheles spp. in Central Lombok Regency

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Majematang Mading

2014-06-01

Full Text Available Malaria remains a public health problem in West Nusa Tenggara Province. Central Lombok District is one of the areas with high case of malaria. Annual Malaria Incidence (AMI was increased from 5.9 ‰ in 2006, 6.7‰ up to 8.1‰ in 2008. The objective of the study is to describe the ecological condition of Anopheles spp. through observation, measurement of environmental variables, larvae and adult collection. This research was an observational research with cross-sectional study. The population of this study is all mosquitos and breeding habitats of Anopheles spp. that exist in the research location. Ecological observations carried out on anopheles breeding habitats including acidity, salinity, shaded places and aquatic biota. Air temperature and humidity measured at the adult mosquitoes trapping sites. The result showed that pH values of water is around 9.00, salinity in the breeding habitats around 14 ppm, and water biota (i.e. moss, grass, shrimps, fishes, tadpoles and crabs surrounded by bushes with larvae density 0,1-28,8 each dipping. The air measurement at the time was between 23°-27° Celsius and 65%-84% humidity. This research concludes that ecology and environmental conditions were supporting the development of larvae and adult mosquito of Anopheles spp.

Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch syndrome founder mutation

DEFF Research Database (Denmark)

Therkildsen, Christina; Isinger-Ekstrand, Anna; Ladelund, Steen

2012-01-01

Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register...... to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation families with comparison to 47 other MLH1 mutant families. The founder mutation conferred comparable risks for colorectal cancer (relative risks, RR, of 0.99 for males and 0.79 for females) and lower risks...... in 68 % with extensive inter-tumor variability despite the same underlying germline mutation. In conclusion, the Danish MLH1 founder mutation that accounts for a significant proportion of Lynch syndrome and is associated with a lower risk for extracolonic cancers....

Physico-chemical characteristics of Anopheles culicifacies and Anopheles varuna breeding water in a dry zone stream in Sri Lanka

DEFF Research Database (Denmark)

Piyaratne, M K; Amerasinghe, F P; Amerasinghe, P H

2005-01-01

BACKGROUND & OBJECTIVES: Selected physico-chemical characteristics of flowing and pooled water in a stream that generated two malaria vectors, Anopheles culicifacies s.l. Giles and Anopheles varuna Iyengar, were investigated during August-September 1997 and July 1998 at the Upper Yan Oya watershed.......5% of 151 samples analysed were mosquito-positive. Logistic regression was used for statistical analysis. RESULTS: Among physico-chemical parameters, An. culicifacies (the major malaria vector in the country) was positively related only to temperature, and An. varuna (a secondary malaria vector) to calcium...

Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry.

Science.gov (United States)

Pande, Mala; Wei, Chongjuan; Chen, Jinyun; Amos, Christopher I; Lynch, Patrick M; Lu, Karen H; Lucio, Laura A; Boyd-Rogers, Stephanie G; Bannon, Sarah A; Mork, Maureen E; Frazier, Marsha L

2012-09-01

The spectrum of cancers seen in a hospital based Lynch syndrome registry of mismatch repair gene mutation carriers was examined to determine the distribution of cancers and examine excess cancer risk. Overall there were 504 cancers recorded in 368 mutation carriers from 176 families. These included 236 (46.8 %) colorectal and 268 (53.2 %) extracolonic cancers. MLH1 mutation carriers had a higher frequency of colorectal cancers whereas MSH2, MSH6 and PMS2 mutation carriers had more extracolonic cancers although these differences were not statistically significant. Men had fewer extracolonic cancers than colorectal (45.3 vs. 54.7 %), whereas women had more extracolonic than colorectal cancers (59.0 vs. 41.0 %). The mean age at diagnosis overall for extracolonic cancers was older than for colorectal, 49.1 versus 44.8 years (P ≤ 0.001). As expected, the index cancer was colorectal in 58.1 % of patients and among the extracolonic index cancers, endometrial was the most common (13.8 %). A significant number of non-Lynch syndrome index cancers were recorded including breast (n = 5) prostate (n = 3), thyroid (n = 3), cervix (n = 3), melanoma (n = 3), and 1 case each of thymoma, sinus cavity, and adenocarcinoma of the lung. However, standardized incidence ratios calculated to assess excess cancer risk showed that only those cancers known to be associated with Lynch syndrome were significant in our sample. We found that Lynch syndrome patients can often present with cancers that are not considered part of Lynch syndrome. This has clinical relevance both for diagnosis of Lynch syndrome and surveillance for cancers of different sites during follow-up of these patients.

Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance.

Science.gov (United States)

Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

2018-03-27

Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2.

Science.gov (United States)

Haraldsdottir, Sigurdis; Rafnar, Thorunn; Frankel, Wendy L; Einarsdottir, Sylvia; Sigurdsson, Asgeir; Hampel, Heather; Snaebjornsson, Petur; Masson, Gisli; Weng, Daniel; Arngrimsson, Reynir; Kehr, Birte; Yilmaz, Ahmet; Haraldsson, Stefan; Sulem, Patrick; Stefansson, Tryggvi; Shields, Peter G; Sigurdsson, Fridbjorn; Bekaii-Saab, Tanios; Moller, Pall H; Steinarsdottir, Margret; Alexiusdottir, Kristin; Hitchins, Megan; Pritchard, Colin C; de la Chapelle, Albert; Jonasson, Jon G; Goldberg, Richard M; Stefansson, Kari

2017-05-03

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.

(AIT) AGAINST ANOPHELES GAMBIAE

African Journals Online (AJOL)

USER

These extracts were tested for repellence against Anopheles gambiae using the human-bait technique ... Synthetic chemicals and insecticides used for control of vectors are causing ... basil, for use as topical repellents against both diurnal and nocturnal .... The physical properties of Euphorbia balsamifera. (Table 1) reveal ...

Differential expression of CK20, β-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X

DEFF Research Database (Denmark)

Haraldsson, Stefan; Klarskov, Louise; Nilbert, Mef

2017-01-01

BACKGROUND: Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other...... than MMR proteins. METHODS: We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX. RESULTS: Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch...... syndrome (p Lynch syndrome tumors compared with FCCTX tumors (p = 0.001,

Achieving behaviour change for detection of Lynch syndrome using the Theoretical Domains Framework Implementation (TDFI) approach: a study protocol.

Science.gov (United States)

Taylor, Natalie; Long, Janet C; Debono, Deborah; Williams, Rachel; Salisbury, Elizabeth; O'Neill, Sharron; Eykman, Elizabeth; Braithwaite, Jeffrey; Chin, Melvin

2016-03-12

Lynch syndrome is an inherited disorder associated with a range of cancers, and found in 2-5 % of colorectal cancers. Lynch syndrome is diagnosed through a combination of significant family and clinical history and pathology. The definitive diagnostic germline test requires formal patient consent after genetic counselling. If diagnosed early, carriers of Lynch syndrome can undergo increased surveillance for cancers, which in turn can prevent late stage cancers, optimise treatment and decrease mortality for themselves and their relatives. However, over the past decade, international studies have reported that only a small proportion of individuals with suspected Lynch syndrome were referred for genetic consultation and possible genetic testing. The aim of this project is to use behaviour change theory and implementation science approaches to increase the number and speed of healthcare professional referrals of colorectal cancer patients with a high-likelihood risk of Lynch syndrome to appropriate genetic counselling services. The six-step Theoretical Domains Framework Implementation (TDFI) approach will be used at two large, metropolitan hospitals treating colorectal cancer patients. Steps are: 1) form local multidisciplinary teams to map current referral processes; 2) identify target behaviours that may lead to increased referrals using discussion supported by a retrospective audit; 3) identify barriers to those behaviours using the validated Influences on Patient Safety Behaviours Questionnaire and TDFI guided focus groups; 4) co-design interventions to address barriers using focus groups; 5) co-implement interventions; and 6) evaluate intervention impact. Chi square analysis will be used to test the difference in the proportion of high-likelihood risk Lynch syndrome patients being referred for genetic testing before and after intervention implementation. A paired t-test will be used to assess the mean time from the pathology test results to referral for high

The bionomics of Anopheles merus (Diptera: Culicidae along the Kenyan coast

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Kipyab Pamela C

2013-02-01

Full Text Available Abstract Background Anopheles merus, a sibling species of the Anopheles gambiae complex occurs along the East African coast but its biology and role in malaria transmission in this region is poorly understood. We evaluated the blood feeding pattern and the role of this species in malaria transmission in Malindi district, Coastal Kenya. Methods Adult mosquitoes were collected indoors by CDC light traps and Pyrethrum Spray Catch and outdoors by CDC light traps. Anopheles females were identified to species by morphological characteristics and sibling species of An. gambiae complex distinguished by rDNA polymerase chain reaction (PCR. Screening for host blood meal sources and presence or absence of Plasmodium falciparum circumsporozoite proteins was achieved by Enzyme Linked Immunosorbent Assays (ELISA. Results Anopheles merus comprised 77.8% of the 387 Anopheles gambiae s.l adults that were collected. Other sibling species of Anopheles gambiae s.l identified in the study site included An. arabiensis(3.6%, and An. gambiae s.s. (8%. The human blood index for An. merus was 0.12, while the sporozoite rate was 0.3%. Conclusion These findings suggest that An. merus can play a minor role in malaria transmission along the Kenyan Coast and should be a target for vector control which in turn could be applied in designing and implementing mosquito control programmes targeting marsh-breeding mosquitoes; with the ultimate goal being to reduce the transmission of malaria associated with these vectors.

Quality colonoscopy and risk of interval cancer in Lynch syndrome

NARCIS (Netherlands)

Haanstra, J. F.; Vasen, H. F. A.; Sanduleanu, S.; van der Wouden, E. J.; Koornstra, J. J.; Kleibeuker, J. H.; Cappel, W. H. de Vos Tot Nederveen

2013-01-01

Despite colonoscopic surveillance, Lynch syndrome patients develop colorectal cancer (CRC). Identification of modifiable factors has the potential to improve outcome of surveillance. The aims of this study were to determine (1) characteristics of patients with CRC, (2) endoscopic and histological

Physical activity and the risk of colorectal cancer in Lynch syndrome.

Science.gov (United States)

Dashti, S Ghazaleh; Win, Aung Ko; Hardikar, Sheetal S; Glombicki, Stephen E; Mallenahalli, Sheila; Thirumurthi, Selvi; Peterson, Susan K; You, Y Nancy; Buchanan, Daniel D; Figueiredo, Jane C; Campbell, Peter T; Gallinger, Steven; Newcomb, Polly A; Potter, John D; Lindor, Noralane M; Le Marchand, Loic; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Basen-Engquist, Karen M; Lynch, Patrick M; Pande, Mala

2018-06-14

Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk for people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n=807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49, and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-h/week) during the age-period of cancer diagnosis or censoring (near-term exposure), and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. Lynch syndrome, however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk for people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk. This article is protected by copyright. All rights reserved. © 2018 UICC.

Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome.

Science.gov (United States)

Medina-Arana, V; Delgado, L; González, L; Bravo, A; Díaz, H; Salido, E; Riverol, D; González-Aguilera, J J; Fernández-Peralta, A M

2011-06-01

Lynch syndrome (LS) is an autosomal dominant condition that predisposes to colorectal cancer and specific other tumors. Extracolonic tumors occur mainly in the endometrium, stomach, ovary, small intestine and urinary tract. The presence of rare tumors in patients belonging to families who have Lynch syndrome is always interesting, because the question arises whether these tumors should be considered as a coincidence or are related with the syndrome. In this last case, they are also the result of the defect in the mismatch repair system, opening the possibility of extending the tumor spectrum associated with the syndrome. Here we describe a patient from a Lynch syndrome family with a germline mutation c.2063T>G (p.M688R) in the MSH2 gene, who developed an adrenal cortical carcinoma, a tumor not usually associated with LS. We analyzed the adrenocortical tumour for microsatellite instability (MSI), LOH and the presence of the germline c.2063T>G (M688R) mutation. The adrenal cortical carcinoma showed the MSH2 mutation, loss of heterozygosity of the normal allele in the MSH2 gene and loss of immunohistochemical expression for MSH2 protein, but no microsatellite instability. Additionally, the adrenal cortical carcinoma did not harbour a TP53 mutation. The molecular study indicates that this adrenal cortical cancer is probably due to the mismatch repair defect.

Abundance, composition and natural infection of Anopheles mosquitoes from two malaria-endemic regions of Colombia

OpenAIRE

Carolina Montoya; Priscila Bascuñán; Julián Rodríguez-Zabala; Margarita M. Correa

2017-01-01

Introduction: In Colombia there are three Anopheles species implicated in malaria transmission as primary vectors; however, the local role of some Anopheles species must still be defined. Objective: To determine the abundance, composition and natural infection rates for Anopheles mosquitoes with Plasmodium spp. in two malaria-endemic regions of Colombia. Materials and methods: Anopheles mosquitoes were collected using the human-landing catches and while resting in livestock corrals in n...

The resting sites and blood-meal sources of Anopheles minimus in Taiwan

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Chen Yung-Chen

2008-06-01

Full Text Available Abstract Background The WHO declared Taiwan free from malaria in 1965, but in 2003 the reporting of two introduced cases in a rural area suggested a possible local transmission of this disease. Therefore, understanding the resting sites and the blood sources of Anopheles minimus is crucial in order to provide information for implementing vector control strategies. Methods During a two-year survey, mosquitoes were collected in houses and their surrounding areas and at the bank of larval habitats by backpack aspirators in 17 villages in rural areas of southern and eastern Taiwan for 1 hr. On the same day, blacklight traps were hung downward overnight. Blood-fed mosquito samples were analysed by PCR. Results Of the 195 total households surveyed by backpack aspirators, no Anopheles adults were collected inside the houses, while a single Anopheles minimus and a single Anopheles maculatus were collected outside of the houses. On the same day, 23 An. minimus, two An. maculatus, two Anopheles ludlowae, two Anopheles sinensis, and one Anopheles tessellatus were collected along the bank of larval habitats. In blacklight traps hung outside of the houses in the villages, 69 An. minimus, 62 An. ludlowae, 31 An. sinensis, and 19 An. maculatus were collected. In larval habitats, 98 An. ludlowae, 64 An. minimus, 49 An. sinensis, and 14 An. maculatus were collected. Of a total of 10 blood-fed samples, An. minimus fed on four animals including bovine (60%, dogs (20%, pig (10%, and non-chicken avian (10%. Conclusion Anopheles minimus, an opportunist feeder in Taiwan, was not collected inside the houses, but was found outside of the houses in villages and surrounding larval habitats. Therefore, an outdoor transmission of malaria is likely to occur and, thus, the bed nets, which are favoured for controlling the late biting of An. minimus, should be a very efficient and effective method for those local residents who sleep outdoors. Additionally, space spray of

Pain evaluation during gynaecological surveillance in women with Lynch syndrome

NARCIS (Netherlands)

Helder-Woolderink, Jorien; de Bock, Geertruida; Hollema, Harry; van Oven, Magda; Mourits, Marian

To evaluate perceived pain during repetitive annual endometrial sampling at gynaecologic surveillance in asymptomatic women with Lynch syndrome (LS) over time and in addition to symptomatic women without LS, undergoing single endometrial sampling. In this prospective study, 52 women with LS or first

Pathological assessment of mismatch repair gene variants in Lynch syndrome

DEFF Research Database (Denmark)

Rasmussen, Lene Juel; Heinen, Christopher D; Royer-Pokora, Brigitte

2012-01-01

Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose...

Anopheles Vectors in Mainland China While Approaching Malaria Elimination.

Science.gov (United States)

Zhang, Shaosen; Guo, Shaohua; Feng, Xinyu; Afelt, Aneta; Frutos, Roger; Zhou, Shuisen; Manguin, Sylvie

2017-11-01

China is approaching malaria elimination; however, well-documented information on malaria vectors is still missing, which could hinder the development of appropriate surveillance strategies and WHO certification. This review summarizes the nationwide distribution of malaria vectors, their bionomic characteristics, control measures, and related studies. After several years of effort, the area of distribution of the principal malaria vectors was reduced, in particular for Anopheles lesteri (synonym: An. anthropophagus) and Anopheles dirus s.l., which nearly disappeared from their former endemic regions. Anopheles sinensis is becoming the predominant species in southwestern China. The bionomic characteristics of these species have changed, and resistance to insecticides was reported. There is a need to update surveillance tools and investigate the role of secondary vectors in malaria transmission. Copyright © 2017 Elsevier Ltd. All rights reserved.

Confirmation of Anopheles (Anopheles calderoni Wilkerson, 1991 (Diptera: Culicidae in Colombia and Ecuador through molecular and morphological correlation with topotypic material

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Ranulfo González

2010-12-01

Full Text Available The morphologically similar taxa Anopheles calderoni, Anopheles punctimacula, Anopheles malefactor and Anopheles guarao are commonly misidentified. Isofamilies collected in Valle de Cauca, Colombia, showed morphological characters most similar to An. calderoni, a species which has never previously been reported in Colombia. Although discontinuity of the postsubcostal pale spots on the costa (C and first radial (R1 wing veins is purportedly diagnostic for An. calderoni, the degree of overlap of the distal postsubcostal spot on C and R1 were variable in Colombian specimens (0.003-0.024. In addition, in 98.2% of larvae, seta 1-X was located off the saddle and seta 3-C had 4-7 branches in 86.7% of specimens examined. Correlation of DNA sequences of the second internal transcribed spacer and mtDNA cytochrome c oxidase subunit I gene (COI barcodes (658 bp of the COI gene generated from Colombian progeny material and wild-caught mosquitoes from Ecuador with those from the Peruvian type series of An. calderoni confirmed new country records. DNA barcodes generated for the closely related taxa, An. malefactor and An. punctimacula are also presented for the first time. Examination of museum specimens at the University of the Valle, Colombia, revealed the presence of An. calderoni in inland localities across Colombia and at elevations up to 1113 m.

Limited impact on self-concept in individuals with Lynch syndrome; results from a national cohort study

DEFF Research Database (Denmark)

Petersen, Helle Vendel; Esplen, Mary Jane; Ladelund, Steen

2011-01-01

. We used the national Danish HNPCC register to collect data on self-concept from 413 individuals with Lynch syndrome. The recently developed Lynch syndrome self-concept scale contains 20 items within two subscales related to stigma-vulnerability and bowel symptom-related anxiety. Significantly higher...... total scores, indicating a greater impact on self-concept, were reported by females and by individuals with experience from cancer in close relatives, whereas individuals with less formal education scored significantly higher on the stigma and vulnerability subscale. Scores in the upper quartile were...... more often reported by women (odds ratio 1.8) and by individuals with less education (OR 1.8). This study provides the first extended use of the Lynch syndrome self-concept scale and suggests that the majority of the Danish mutation carriers adapt well to the situation, though knowledge about...

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2

Science.gov (United States)

Haraldsdottir, Sigurdis; Rafnar, Thorunn; Frankel, Wendy L.; Einarsdottir, Sylvia; Sigurdsson, Asgeir; Hampel, Heather; Snaebjornsson, Petur; Masson, Gisli; Weng, Daniel; Arngrimsson, Reynir; Kehr, Birte; Yilmaz, Ahmet; Haraldsson, Stefan; Sulem, Patrick; Stefansson, Tryggvi; Shields, Peter G.; Sigurdsson, Fridbjorn; Bekaii-Saab, Tanios; Moller, Pall H.; Steinarsdottir, Margret; Alexiusdottir, Kristin; Hitchins, Megan; Pritchard, Colin C.; de la Chapelle, Albert; Jonasson, Jon G.; Goldberg, Richard M.; Stefansson, Kari

2017-01-01

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000–2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations. PMID:28466842

A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome.

Science.gov (United States)

Clendenning, M; Senter, L; Hampel, H; Robinson, K Lagerstedt; Sun, S; Buchanan, D; Walsh, M D; Nilbert, M; Green, J; Potter, J; Lindblom, A; de la Chapelle, A

2008-06-01

When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within PMS2 has been limited (PMS2. This disparity is primarily due to complications in the study of this gene caused by interference from pseudogene sequences. Using a recently developed method for detecting PMS2 specific mutations, we have screened 99 patients who are likely candidates for PMS2 mutations based on immunohistochemical analysis. We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n = 61). These individuals all display the rare allele (population frequency 10 000 carriers of this mutation in the USA alone. The identification of both the mutation and the common haplotype in one Swedish control sample (n = 225), along with evidence that Lynch syndrome associated cancers are rarer than expected in the probands' families, would suggest that this is a prevalent mutation with reduced penetrance.

Freshwater and Saline Loads of Dissolved Inorganic Nitrogen to Hood Canal and Lynch Cove, Western Washington

Science.gov (United States)

Paulson, Anthony J.; Konrad, Christopher P.; Frans, Lonna M.; Noble, Marlene; Kendall, Carol; Josberger, Edward G.; Huffman, Raegan L.; Olsen, Theresa D.

2006-01-01

Hood Canal is a long (110 kilometers), deep (175 meters) and narrow (2 to 4 kilometers wide) fjord of Puget Sound in western Washington. The stratification of a less dense, fresh upper layer of the water column causes the cold, saltier lower layer of the water column to be isolated from the atmosphere in the late summer and autumn, which limits reaeration of the lower layer. In the upper layer of Hood Canal, the production of organic matter that settles and consumes dissolved oxygen in the lower layer appears to be limited by the load of dissolved inorganic nitrogen (DIN): nitrate, nitrite, and ammonia. Freshwater and saline loads of DIN to Hood Canal were estimated from available historical data. The freshwater load of DIN to the upper layer of Hood Canal, which could be taken up by phytoplankton, came mostly from surface and ground water from subbasins, which accounts for 92 percent of total load of DIN to the upper layer of Hood Canal. Although DIN in rain falling on land surfaces amounts to about one-half of the DIN entering Hood Canal from subbasins, rain falling directly on the surface of marine waters contributed only 4 percent of the load to the upper layer. Point-source discharges and subsurface flow from shallow shoreline septic systems contributed less than 4 percent of the DIN load to the upper layer. DIN in saline water flowing over the sill into Hood Canal from Admiralty Inlet was at least 17 times the total load to the upper layer of Hood Canal. In September and October 2004, field data were collected to estimate DIN loads to Lynch Cove - the most inland marine waters of Hood Canal that routinely contain low dissolved-oxygen waters. Based on measured streamflow and DIN concentrations, surface discharge was estimated to have contributed about one-fourth of DIN loads to the upper layer of Lynch Cove. Ground-water flow from subbasins was estimated to have contributed about one-half of total DIN loads to the upper layer. In autumn 2004, the relative

Elisa Alicia Lynch: a Dama de Aço do Paraguai * Elisa Alicia Lynch: the Steel ‘S Lady of Paraguay

OpenAIRE

Frota, Luciara Silveira de Aragão e

2015-01-01

Este trabalho mostra uma nova visão da irlandesa Elisa Alicia Lynch, longe da figura de prostituta manipuladora que incitou o Marechal Solano López no começo da Guerra do Paraguai. Dentro de uma corrente revisionista histórica, apoiada em Marc Bloch, propõe uma nova análise de seu papel na vida de Solano López e do Paraguai, comentando a literatura sobre o assunto.

Distinct population structure for co-occurring Anopheles goeldii and Anopheles triannulatus in Amazonian Brazil

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Sascha Naomi McKeon

2013-08-01

Full Text Available To evaluate whether environmental heterogeneity contributes to the genetic heterogeneity in Anopheles triannulatus, larval habitat characteristics across the Brazilian states of Roraima and Pará and genetic sequences were examined. A comparison with Anopheles goeldii was utilised to determine whether high genetic diversity was unique to An. triannulatus. Student t test and analysis of variance found no differences in habitat characteristics between the species. Analysis of population structure of An. triannulatus and An. goeldii revealed distinct demographic histories in a largely overlapping geographic range. Cytochrome oxidase I sequence parsimony networks found geographic clustering for both species; however nuclear marker networks depicted An. triannulatus with a more complex history of fragmentation, secondary contact and recent divergence. Evidence of Pleistocene expansions suggests both species are more likely to be genetically structured by geographic and ecological barriers than demography. We hypothesise that niche partitioning is a driving force for diversity, particularly in An. triannulatus.

Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review.

Science.gov (United States)

Yokoyama, Takanori; Takehara, Kazuhiro; Sugimoto, Nao; Kaneko, Keika; Fujimoto, Etsuko; Okazawa-Sakai, Mika; Okame, Shinichi; Shiroyama, Yuko; Yokoyama, Takashi; Teramoto, Norihiro; Ohsumi, Shozo; Saito, Shinya; Imai, Kazuho; Sugano, Kokichi

2018-05-21

Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer. Here we report a woman who developed endometrial cancer at the age of 49 years. She had a family history of colorectal cancer (first-degree relative aged 52 years) and stomach cancer (second-degree relative with the age of onset unknown). No other family history was present, and she failed to meet the Amsterdam II criteria for the diagnosis of Lynch syndrome. Losses of MLH1 and PMS2, but not MSH2 and MSH6, proteins were observed by IHC in endometrial cancer tissues. Because MLH1 promoter hypermethylation was detected in endometrial cancer tissue samples, the epigenetic silencing of MLH1 was suspected as the cause of the protein loss. However, because of the early onset of endometrial cancer and the positive family history, a diagnosis of Lynch syndrome was also suspected. Therefore, we provided her with genetic counseling. After obtaining her consent, MLH1 promoter methylation testing and genetic testing of peripheral blood were performed. MLH1 promoter methylation was not observed in peripheral blood. However, genetic testing revealed a large deletion of exon 5 in MLH1; thus, we diagnosed the presence of Lynch syndrome. Both MLH1 germline mutation and MLH1 promoter hypermethylation may be observed in endometrial cancer. Therefore, even if MLH1 promoter hypermethylation is detected, a diagnosis of Lynch syndrome cannot be excluded.

Small bowel endoscopy in familial adenomatous polyposis and Lynch syndrome

NARCIS (Netherlands)

Koornstra, Jan Jacob

Patients with familial adenomatous polyposis (FAP) and patients with Lynch syndrome have an increased risk of developing small intestinal neoplasia. In both conditions, the lifetime risk to develop small bowel cancer is estimated to be around 5%. In FAP, this risk is associated with the degree of

Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome).

Science.gov (United States)

Buchanan, Daniel D; Rosty, Christophe; Clendenning, Mark; Spurdle, Amanda B; Win, Aung Ko

2014-01-01

Carriers of a germline mutation in one of the DNA mismatch repair (MMR) genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome). MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening) is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification) and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the data from published studies are combined, 59% (95% confidence interval [CI]: 55% to 64%) of colorectal cancers and 52% (95% CI: 41% to 62%) of endometrial cancers with MMR deficiency were identified as suspected Lynch syndrome. Recent studies estimated that colorectal cancer risk for relatives of suspected Lynch syndrome cases is lower than for relatives of those with MMR gene mutations, but higher than for relatives of those with tumor MMR deficiency resulting from methylation of the MLH1 gene promoter. The cause of tumor MMR deficiency in suspected Lynch syndrome cases is likely due to either unidentified germline MMR gene mutations, somatic cell mosaicism, or biallelic somatic

Genetic anticipation in Swedish Lynch syndrome families

OpenAIRE

von Salomé, Jenny; Boonstra, Philip S.; Karimi, Masoud; Silander, Gustav; Stenmark-Askmalm, Marie; Gebre-Medhin, Samuel; Aravidis, Christos; Nilbert, Mef; Lindblom, Annika; Lagerstedt-Robinson, Kristina

2017-01-01

Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS) caused by mutations in DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have an earlier onset compared to the general population. However, age at first primary cancer varies within families and genetic anticipation, i.e. decreasing age at onset in successive generations, ha...

Assessing Genetic Variants of Uncertain Significance: The Example of Lynch Syndrome

DEFF Research Database (Denmark)

Rasmussen, Lene Juel; Heinen, Christopher D.

2014-01-01

cancer syndrome, Lynch syndrome, is used as an example. This challenge is addressed by illustrating the importance of combining genetic and functional data in future strategies to assess VUS. The proposed strategies combine clinical genetic, analytical, functional and in silico approaches....

Barriers and Motivators for Referral of Patients with Suspected Lynch Syndrome to Cancer Genetic Services: A Qualitative Study

Science.gov (United States)

Tan, Yen Y.; Fitzgerald, Lisa J.

2014-01-01

This article explores the views of general practitioners and specialists on their referral of patients with suspected Lynch syndrome to cancer genetic services. Using a purposive maximum variation sampling strategy, we conducted semi-structured interviews face-to-face with 28 general practitioners and specialists in public or private hospitals and specialist clinics between March and August 2011. General practitioners and specialists were recruited in a major metropolitan area in Australia. Interview transcripts were reviewed by two independent researchers, and thematic analysis was performed using NVivo10 software. The main barriers and motivators identified were: (1) clinician-related (e.g., familiarity with Lynch syndrome and family history knowledge); (2) patient-related (e.g., patients’ interests and personal experience with cancer); and (3) organizational-related (e.g., access to services, guidelines and referral pathway). Referral of patients with suspected Lynch syndrome to cancer genetic services is motivated and hindered by a range of individual, interpersonal and organizational factors. In order to improve the care and quality of life of patients and family with suspected Lynch syndrome, further research is needed to develop supportive tools for clinicians. PMID:25562140

Barriers and Motivators for Referral of Patients with Suspected Lynch Syndrome to Cancer Genetic Services: A Qualitative Study

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Yen Y. Tan

2014-02-01

Full Text Available This article explores the views of general practitioners and specialists on their referral of patients with suspected Lynch syndrome to cancer genetic services. Using a purposive maximum variation sampling strategy, we conducted semi-structured interviews face-to-face with 28 general practitioners and specialists in public or private hospitals and specialist clinics between March and August 2011. General practitioners and specialists were recruited in a major metropolitan area in Australia. Interview transcripts were reviewed by two independent researchers, and thematic analysis was performed using NVivo10 software. The main barriers and motivators identified were: (1 clinician-related (e.g., familiarity with Lynch syndrome and family history knowledge; (2 patient-related (e.g., patients’ interests and personal experience with cancer; and (3 organizational-related (e.g., access to services, guidelines and referral pathway. Referral of patients with suspected Lynch syndrome to cancer genetic services is motivated and hindered by a range of individual, interpersonal and organizational factors. In order to improve the care and quality of life of patients and family with suspected Lynch syndrome, further research is needed to develop supportive tools for clinicians.

Urban agriculture and Anopheles habitats in Dar es Salaam, Tanzania.

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Dongus, Stefan; Nyika, Dickson; Kannady, Khadija; Mtasiwa, Deo; Mshinda, Hassan; Gosoniu, Laura; Drescher, Axel W; Fillinger, Ulrike; Tanner, Marcel; Killeen, Gerry F; Castro, Marcia C

2009-05-01

A cross-sectional survey of agricultural areas, combined with routinely monitored mosquito larval information, was conducted in urban Dar es Salaam, Tanzania, to investigate how agricultural and geographical features may influence the presence of Anopheles larvae. Data were integrated into a geographical information systems framework, and predictors of the presence of Anopheles larvae in farming areas were assessed using multivariate logistic regression with independent random effects. It was found that more than 5% of the study area (total size 16.8 km2) was used for farming in backyard gardens and larger open spaces. The proportion of habitats containing Anopheles larvae was 1.7 times higher in agricultural areas compared to other areas (95% confidence interval = 1.56-1.92). Significant geographic predictors of the presence of Anopheles larvae in gardens included location in lowland areas, proximity to river, and relatively impermeable soils. Agriculture-related predictors comprised specific seedbed types, mid-sized gardens, irrigation by wells, as well as cultivation of sugar cane or leafy vegetables. Negative predictors included small garden size, irrigation by tap water, rainfed production and cultivation of leguminous crops or fruit trees. Although there was an increased chance of finding Anopheles larvae in agricultural sites, it was found that breeding sites originated by urban agriculture account for less than a fifth of all breeding sites of malaria vectors in Dar es Salaam. It is suggested that strategies comprising an integrated malaria control effort in malaria-endemic African cities include participatory involvement of farmers by planting shade trees near larval habitats.

Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome.

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Reuschenbach, Miriam; Kloor, Matthias; Morak, Monika; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Tariverdian, Mirjam; Findeisen, Peter; Neumaier, Michael; Holinski-Feder, Elke; von Knebel Doeberitz, Magnus

2010-06-01

High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n = 69), healthy Lynch syndrome mutation carriers (n = 31) and healthy controls (n = 52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (P = 0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients.

Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome

Science.gov (United States)

Reuschenbach, Miriam; Kloor, Matthias; Morak, Monika; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Tariverdian, Mirjam; Findeisen, Peter; Neumaier, Michael; Holinski-Feder, Elke; Doeberitz, Magnus von Knebel

2014-01-01

High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer (HNPCC) or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites (cMS) and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n=69), healthy Lynch syndrome mutation carriers (n=31) and healthy controls (n=52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (p=0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients. PMID:19957108

Revised guidelines for the clinical management of Lynch syndrome (HNPCC)

DEFF Research Database (Denmark)

Vasen, Hans F A; Blanco, Ignacio; Aktan-Collan, Katja

2013-01-01

Lynch syndrome (LS) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. In 2007, a group of European experts (the Mallorca group) published guidelines...

BIONOMIK VEKTOR MALARIA NYAMUK Anopheles sundaicus dan Anopheles letifer DI KECAMATAN BELAKANG PADANG , BATAM, KEPULAUAN RIAU

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Shinta Shinta

2012-11-01

Full Text Available Abstract Malaria continues to be a public health problem in the malaria endemic areas in Indonesia and often cause an outbreak. Batam municipality is the priority for development area in the Riau island Province, nevertheless malaria is still a public health problem. The national government and district office government have been committed to have a program for eliminating malaria at Batam area in year 2015. One of the malaria control program is the vector control measure. The failure of vector control is partly due to a lack of understanding of vector behavior in its epidemiological setting. The understanding of  malaria vector species and its behavior will be useful to plan the vector control intervention.  The study of bio-ecology of malaria vector is very important factor to  understand its behavior and to formulate the vector control strtegy in Batam area. This study was carried out at Belakang Padang, Batam in 2008 using breeding habitat survey of Anopheles spp, measuring the pH, salinity and observation of breeding characteristics, mapping of breeding sites distribution using GPS and human landing collection inside as well as outside houses and ELISA for circumsporozoite.  The results of the study revealed that, in the Belakang padang areas were found five natural breeding habitat of Anopheles spp. e.i: marshy areas, marshy with mangrove tree in the peripher, creek, mud-hole and water reservoir (water dam. Larvae of  An. letifer and An sundaicus were found relatively higher number in the marshy areas, with characteristis of pH: 5-7,5,  temperature 28-330C and salinity was 0-28 ‰.  Only one species of anopheline An. sundaicus  was found in the adult stage in Belakang Padang area, though An. letifer was found only in the larva stage.  The biting activities of An. sundaicus throughout the night both indoors and outdoors, though the biting peak occured at 02.00-03.00 am.  Both  An sundaicus and An. letifer at  Belakang Padang

Novel Implications in Molecular Diagnosis of Lynch Syndrome

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Raffaella Liccardo

2017-01-01

Full Text Available About 10% of total colorectal cancers are associated with known Mendelian inheritance, as Familial Adenomatous Polyposis (FAP and Lynch syndrome (LS. In these cancer types the clinical manifestations of disease are due to mutations in high-risk alleles, with a penetrance at least of 70%. The LS is associated with germline mutations in the DNA mismatch repair (MMR genes. However, the mutation detection analysis of these genes does not always provide informative results for genetic counseling of LS patients. Very often, the molecular analysis reveals the presence of variants of unknown significance (VUSs whose interpretation is not easy and requires the combination of different analytical strategies to get a proper assessment of their pathogenicity. In some cases, these VUSs may make a more substantial overall contribution to cancer risk than the well-assessed severe Mendelian variants. Moreover, it could also be possible that the simultaneous presence of these genetic variants in several MMR genes that behave as low risk alleles might contribute in a cooperative manner to increase the risk of hereditary cancer. In this paper, through a review of the recent literature, we have speculated a novel inheritance model in the Lynch syndrome; this could pave the way toward new diagnostic perspectives.

A reliable morphological method to assess the age of male Anopheles gambiae

NARCIS (Netherlands)

Huho, B.J.; Ng'habi, K.R.; Killeen, G.F.; Nkwengulila, G.; Knols, B.G.J.; Ferguson, H.M.

2006-01-01

Background - Release of genetically-modified (GM) or sterile male mosquitoes for malaria control is hampered by inability to assess the age and mating history of free-living male Anopheles. Methods - Age and mating-related changes in the reproductive system of male Anopheles gambiae were quantified

Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum.

Science.gov (United States)

Yamaguchi, Tatsuro; Furukawa, Yoichi; Nakamura, Yusuke; Matsubara, Nagahide; Ishikawa, Hideki; Arai, Masami; Tomita, Naohiro; Tamura, Kazuo; Sugano, Kokichi; Ishioka, Chikashi; Yoshida, Teruhiko; Moriya, Yoshihiro; Ishida, Hideyuki; Watanabe, Toshiaki; Sugihara, Kenichi

2015-02-01

The characteristics of familial colorectal cancer type X are poorly defined. Here we aimed to clarify the differences in clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients. We performed germline mutation analyses of mismatch repair genes in 125 patients. Patients who met the Amsterdam Criteria I but lacked mismatch repair gene mutations were diagnosed with suspected familial colorectal cancer type X. We identified 69 patients with Lynch syndrome and 25 with suspected familial colorectal cancer type X. The frequencies of gastric and extracolonic Lynch syndrome-associated cancers were lower with suspected familial colorectal cancer type X than with Lynch syndrome. The number of organs with Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. The cumulative incidence of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. We estimated that the median cancer risk in 60-year-old patients with Lynch syndrome was 89, 36 and 24% for colorectal, endometrial and gastric cancers, respectively. Analyses of family members, including probands, revealed that the median age at diagnosis of extracolonic Lynch syndrome-associated cancer was significantly older with suspected familial colorectal cancer type X than with Lynch syndrome. The frequency of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. A significant difference in extracolonic Lynch syndrome-associated cancer was evident between suspected familial colorectal cancer type X and Lynch syndrome. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

BIONOMIK NYAMUK MANSONIA DAN ANOPHELES DI DESA KARYA MAKMUR, KABUPATEN OKU TIMUR

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Yanelza Supranelfy

2016-09-01

Full Text Available Abstract Lymphatic filariasis is still become the health problem in Indonesia, the disease almost found inthe entire area with fairly high level endemicity. Karya Makmur Village, Madang Suku III District, EastOgan Komering Ulu Regency, South Sumatera Province in 2007 has micofilariae rate of 1,05% based fromblood survey. The aims of the research is to identify vector and the breeding habitat. This research has beenconducted in Karya Makmur Village from May to November 2011. This type of research is noninterventionstudy with spot survey research design. Mosquitoes collection using human landing andresting collection methods, while mosquito larvae were collected from breeding sites. This research found14 species of Mansonia and Anopheles were collected and the species were Mansonia uniformis, Ma.annulata, Ma. indiana, Ma. dives, Ma. bonneae, Ma. annulifera, Anopheles nigerrimus , An. annularis, An.maculatus, An. letifer, An. vagus, An. barbumbrosus, An. barbirostris and An. tesselatus. Mansoniauniformis and Anopheles nigerrimus was confirmed as filariasis vector but none containing microfilariae.Breeding habitat of Anopheles have water temperature 280C — 300C and pH 7 with vegetation (grass andEichhornia crassipes / water hyacinth and predator (Oreochromis niloticus / nile tilapia and Aplocheiluspanchax / fish head lead. Thus the community are expected to behave positively, especially avoidmosquito bites and manipulate the environment that potentially as mosquito larvae breeding habitat.Keywords: Mansonia, Anopheles, filariasis, Karya Makmur Village AbstrakFilariasis limfatik masih merupakan masalah kesehatandi Indonesia, penyebaran penyakit ini hampirdi seluruh wilayah dan dibeberapa daerah dengan tingkatendemic yang cukup tinggi. Desa Karya Makmur, Kecamatan Madang SukuIII, Kabupaten Ogan KomeringUlu Timur, Propinsi Sumatera Selatan pada tahun2007, mikrofilariarate sebesar1,05% berdasarkansurvey darah jari. Tujuan penelitian untuk mengetahui

The Germline MLH1 K618A Variant and Susceptibility to Lynch Syndrome-Associated Tumors

Science.gov (United States)

Medeiros, Fabiola; Lindor, Noralane M.; Couch, Fergus J.; Highsmith, W. Edward

2013-01-01

Missense variants discovered during sequencing of cancer susceptibility genes can be problematic for clinical interpretation. MLH1 K618A, which results from a 2-bp alteration (AAG→GCG) leading to a substitution of lysine to alanine in codon 618, has variously been interpreted as a pathogenic mutation, a variant of unknown significance, and a benign polymorphism. We evaluated the role of MLH1 K618A in predisposition to cancer by genotyping 1512 control subjects to assess its frequency in the general population. We also reviewed the literature concerning MLH1 K618A in families with colorectal cancer. The measured allele frequency of the K618A variant was 0.40%, which is remarkably close to the 0.44% summarized from 2491 control subjects in the literature. K618A was over-represented in families with suspected Lynch syndrome. In 1366 families, the allele frequency was 0.88% (OR = 2.1, 95% CI = 1.3 to 3.5; P = 0.006). In studies of sporadic cancers of the type associated with Lynch syndrome, K618A was over-represented in 1742 cases (allele frequency of 0.83) (OR = 2.0, 95% CI = 1.2 to 3.2; P = 0.008). We conclude that MLH1 K618A is not a fully penetrant Lynch syndrome mutation, although it is not without effect, appearing to increase the risk of Lynch syndrome-associated tumors approximately twofold. Our systematic assessment approach may be useful for variants in other genes. PMID:22426235

Factors influencing the spatial distribution of Anopheles larvae in Coimbatore District, Tamil Nadu, India.

Science.gov (United States)

Arjunan, Naresh Kumar; Kadarkarai, Murugan; Kumar, Shobana; Pari, Madhiyazhagan; Thiyagarajan, Nataraj; Vincent, C Thomas; Barnard, Donald R

2015-12-01

Malaria causes extensive morbidity and mortality in humans and results in significant economic losses in India. The distribution of immature malaria-transmitting Anopheles mosquitoes was studied in 17 villages in Coimbatore District as a prelude to the development and implementation of vector control strategies that are intended to reduce the risk of human exposure to potentially infectious mosquitoes. Eight Anopheles species were recorded. The most numerous species were Anopheles vagus, Anopheles subpictus, and Anopheles hyrcanus. The location of mosquito development sites and the density of larvae in each village was evaluated for correlation with selected demographic, biologic, and land use parameters using remote sensing and geographic information systems (GIS) technology. We found the number of mosquito development sites in a village and the density of larvae in such sites to be positively correlated with human population density but not the surface area (km(2)) of the village. The number of mosquito development sites and the density of larvae in each site were not correlated. Data from this study are being used to construct a GIS-based mapping system that will enable the location of aquatic habitats with Anopheles larvae in the Coimbatore District, Tamil Nadu, India as target sites for the application of vector control. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic variants in the cell cycle control pathways contribute to early onset colorectal cancer in Lynch syndrome.

Science.gov (United States)

Chen, Jinyun; Etzel, Carol J; Amos, Christopher I; Zhang, Qing; Viscofsky, Nancy; Lindor, Noralane M; Lynch, Patrick M; Frazier, Marsha L

2009-11-01

Lynch syndrome is an autosomal dominant syndrome of familial malignancies resulting from germ line mutations in DNA mismatch repair (MMR) genes. Our goal was to take a pathway-based approach to investigate the influence of polymorphisms in cell cycle-related genes on age of onset for Lynch syndrome using a tree model. We evaluated polymorphisms in a panel of cell cycle-related genes (AURKA, CDKN2A, TP53, E2F2, CCND1, TP73, MDM2, IGF1, and CDKN2B) in 220 MMR gene mutation carriers from 129 families. We applied a novel statistical approach, tree modeling (Classification and Regression Tree), to the analysis of data on patients with Lynch syndrome to identify individuals with a higher probability of developing colorectal cancer at an early age and explore the gene-gene interactions between polymorphisms in cell cycle genes. We found that the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 variant genotype, AURKA wild-type genotype, and CCND1 variant genotype had the youngest age of onset, with a 45-year median onset age, while the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 wild-type genotype, and AURKA variant genotype had the latest median age of onset, which was 70 years. Furthermore, we found evidence of a possible gene-gene interaction between E2F2 and AURKA genes related to CRC age of onset. Polymorphisms in these cell cycle-related genes work together to modify the age at the onset of CRC in patients with Lynch syndrome. These studies provide an important part of the foundation for development of a model for stratifying age of onset risk among those with Lynch syndrome.

Patient-reported disease knowledge and educational needs in Lynch syndrome: findings of an interactive multidisciplinary patient conference.

Science.gov (United States)

Bannon, Sarah A; Mork, Maureen; Vilar, Eduardo; Peterson, Susan K; Lu, Karen; Lynch, Patrick M; Rodriguez-Bigas, Miguel A; You, Yiqian Nancy

2014-02-05

Patients with Lynch Syndrome, the most common hereditary colorectal cancer syndrome, benefit from genetic education and family counseling regarding diagnostic testing and cancer surveillance/prevention recommendations. Although genetic counseling is currently the most common venue where such education and counseling takes place, little is known about the level of disease knowledge and education needs as directly reported by patients and families with Lynch Syndrome. Furthermore, experiences with forums for larger-scale knowledge transfer have been limited in the current literature. We conducted a one-day interactive multidisciplinary patient conference, designed to complement individual genetic counseling for updating disease knowledge, supportive networking and needs assessment among Lynch Syndrome patients and their family members. The patient conference was designed utilizing the conceptual framework of action research. Paired pre- and post-conference surveys were administered to 44 conference participants anonymously to assess patient-reported disease knowledge and education needs. A multidisciplinary team of expert providers utilized a variety of educational formats during the one-day conference. Four main focus areas were: genetic testing, surveillance/prevention, living with Lynch Syndrome, and update on research. Thirty-two participants (73%) completed the pre-conference, and 28 (64%) participants completed the post-conference surveys. Nineteen respondents were affected and the remaining were unaffected. The scores of the disease-knowledge items significantly increased from 84% pre- to 92% post-conference (p = 0.012). Patients reported a high level of satisfaction and identified further knowledge needs in nutrition (71%), surveillance/prevention options (71%), support groups (36%), cancer risk assessment (32%), active role in medical care (32%), and research opportunities (5%). Our experience with a dedicated patient education conference focused on

Lynch syndrome associated with two MLH1 promoter variants and allelic imbalance of MLH1 expression.

Science.gov (United States)

Hesson, Luke B; Packham, Deborah; Kwok, Chau-To; Nunez, Andrea C; Ng, Benedict; Schmidt, Christa; Fields, Michael; Wong, Jason W H; Sloane, Mathew A; Ward, Robyn L

2015-06-01

Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) within the MLH1 5'untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expression and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A>G and c.-7C>T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5'UTR in the pathogenesis of Lynch syndrome. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

The Failure of Lehman Brothers and Merril Lynch: A Lesson for the ...

African Journals Online (AJOL)

DR Nneka

the United State America treasury securities market. Ahimie (2008) ... Thus, the above school of thought considered a bank failure as not when it ceases .... Lynch had further confirmed the historical fact that, no bank or financial institution is.

Thyroid cancer in a patient with a germline MSH2 mutation. Case report and review of the Lynch syndrome expanding tumour spectrum

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Stulp Rein P

2008-02-01

Full Text Available Abstract Lynch syndrome (HNPCC is a dominantly inherited disorder characterized by germline defects in DNA mismatch repair (MMR genes and the development of a variety of cancers, predominantly colorectal and endometrial. We present a 44-year-old woman who was shown to carry the truncating MSH2 gene mutation that had previously been identified in her family. Recently, she had been diagnosed with an undifferentiated carcinoma of the thyroid and an adenoma of her coecum. Although the thyroid carcinoma was not MSI-high (1 out of 5 microsatellites instable, it did show complete loss of immunohistochemical expression for the MSH2 protein, suggesting that this tumour was not coincidental. Although the risks for some tumour types, including breast cancer, soft tissue sarcoma and prostate cancer, are not significantly increased in Lynch syndrome, MMR deficiency in the presence of a corresponding germline defect has been demonstrated in incidental cases of a growing range of tumour types, which is reviewed in this paper. Interestingly, the MSH2-associated tumour spectrum appears to be wider than that of MLH1 and generally the risk for most extra-colonic cancers appears to be higher for MSH2 than for MLH1 mutation carriers. Together with a previously reported case, our findings show that anaplastic thyroid carcinoma can develop in the setting of Lynch syndrome. Uncommon Lynch syndrome-associated tumour types might be useful in the genetic analysis of a Lynch syndrome suspected family if samples from typical Lynch syndrome tumours are unavailable.

Surveillance colonoscopy practice in Lynch syndrome in the Netherlands : A nationwide survey

NARCIS (Netherlands)

Koornstra, Jan J.; Vasen, Hans Fa

2007-01-01

Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is the most common genetic disorder predisposing to colorectal cancer. As regular colonoscopic surveillance has been shown to reduce the incidence of colorectal cancer, this strategy is recommended worldwide. Recently, several

Community Practice Implementation of a Self-administered Version of PREMM1,2,6 to Assess Risk for Lynch Syndrome.

Science.gov (United States)

Luba, Daniel G; DiSario, James A; Rock, Colleen; Saraiya, Devki; Moyes, Kelsey; Brown, Krystal; Rushton, Kristen; Ogara, Maydeen M; Raphael, Mona; Zimmerman, Dayna; Garrido, Kimmie; Silguero, Evelyn; Nelson, Jonathan; Yurgelun, Matthew B; Kastrinos, Fay; Wenstrup, Richard J; Syngal, Sapna

2018-01-01

Lynch syndrome is a genetic disorder that greatly increases risk for colorectal and other cancers, although it is underdiagnosed. Prediction of MLH1, MSH2, and MSH6 (PREMM 1,2,6 ) is a web-based tool that analyzes individuals' personal/family histories of cancer to quantify their likelihood of carrying a germline mutation associated with Lynch syndrome. We investigated the feasibility of systematic risk assessment for Lynch syndrome in a community gastroenterology practice using a patient-completed version of PREMM 1,2,6 . PREMM 1,2,6 was adapted into a computer tablet version designed for self-administration by patients. Individuals presenting to a community gastroenterology office and endoscopy facility in California completed the PREMM 1,2,6 assessment before their visit (n = 3134). The total study duration (8 months) comprised a 2-month initiation period (May 1-June 30, 2013) and a 6-month study period (July 1-December 31, 2013). Genetic counseling and germline analysis for mutations in genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM) were offered to individuals with PREMM 1,2,6 scores of 5% or higher. Patients and providers completed surveys to evaluate the feasibility and satisfaction with the process. Of the 3134 individuals assessed by PREMM 1,2,6 during the 6-month study period, 177 individuals (5.6%) had scores of 5% or higher. Of these, 146 individuals underwent genetic testing, along with 28 additional participants recruited nonconsecutively during the initiation period. Mutations associated with Lynch syndrome were detected in 3 of the 146 individuals (2.1%) with PREMM 1,2,6 scores of 5% or higher who underwent germline testing, and 3 of the 28 patients (10.7%) recruited during study initiation with PREMM 1,2,6 scores of 5% or higher. Of the participants who underwent genetic analysis, 98.6% stated that they understood the information provided to them. All of the surveyed providers stated that they were satisfied with the

Initiation of universal tumor screening for Lynch syndrome in colorectal cancer patients as a model for the implementation of genetic information into clinical oncology practice.

Science.gov (United States)

Cohen, Stacey A; Laurino, Mercy; Bowen, Deborah J; Upton, Melissa P; Pritchard, Colin; Hisama, Fuki; Jarvik, Gail; Fichera, Alessandro; Sjoding, Britta; Bennett, Robin L; Naylor, Lorraine; Jacobson, Angela; Burke, Wylie; Grady, William M

2016-02-01

Lynch syndrome confers a hereditary predisposition to colorectal and other cancers. Universal tumor screening (UTS) for Lynch syndrome is recommended by several professional societies, but the implementation can be complex. This article describes the evaluation, process development, and initiation of Lynch syndrome UTS at a tertiary referral cancer center. A multidisciplinary team developed the new process design. Issues in 5 themes were noted: timing, funding, second-opinion patients, result processing, and the role of genetics providers. A committee approach was used to examine each issue for process-improvement development. The issues related to testing were addressed individually for the successful implementation of UTS at the institutional level. In the conventional-care period, 9 of 30 cases (30%) received Lynch syndrome screening, and 4 cases were referred to medical genetics. During the 6 months following the implementation of UTS, 32 of 44 patients (73%) received Lynch syndrome screening. The 13 unscreened patients all had identified reasons for nonscreening (eg, financial limitations). Ten patients were referred to medical genetics, which identified no new cases of Lynch syndrome, but a low-risk adenomatous polyposis coli (APC) variant was detected in 1 individual. The implementation of effective Lynch syndrome UTS can feasibly alter practice at the institutional level. This experience with the assessment and management of issues relevant to the successful implementation of a new clinical care paradigm based on emerging technology has implications for the uptake of advances across molecular oncology into clinical practice, and this is highly relevant in the current era of rapidly evolving genomic technology. © 2015 American Cancer Society.

Dietary patterns and colorectal adenomas in Lynch syndrome: the GEOLynch cohort study

NARCIS (Netherlands)

Botma, A.; Vasen, H.F.; Duijnhoven, F.J.B. van; Kleibeuker, J.H.; Nagengast, F.M.; Kampman, E.

2013-01-01

BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

Dietary Patterns and Colorectal Adenomas in Lynch Syndrome: The GEOLynch Cohort Study

NARCIS (Netherlands)

Botma, A.; Vasen, H.F.; Duijnhoven, van F.J.B.; Kleibeuker, J.H.; Nagengast, F.M.; Kampman, E.

2013-01-01

BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

Dietary Patterns and Colorectal Adenomas in Lynch Syndrome The GEOLynch Cohort Study

NARCIS (Netherlands)

Botma, Akke; Vasen, Hans F. A.; van Duijnhoven, Franzel J. B.; Kleibeuker, Jan H.; Nagengast, Fokko M.; Kampman, Ellen

2013-01-01

BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

Sessile serrated polyps of the colorectum are rare in patients with Lynch syndrome and in familial colorectal cancer families

DEFF Research Database (Denmark)

Andersen, S H; Lykke, E; Folker, M B

2008-01-01

Whereas the generally accepted carcinogenesis pathway of the microsatellite instabile high (MSI-H) colorectal carcinoma (CRC) involves the traditional adenoma in patients with Lynch syndrome, a serrate pathway involving serrate adenomas (SA) and sessile serrate polyps (SSP) characterize...... the sporadic MSI-H counterpart. Recent studies have, however, challenged such simple one-pathway models, inviting the consideration of alternative, unexpected pathways. Here, the issue as to the possible role of SSP, primarily in the context of Lynch syndrome, but also in subjects from familial CRC families...... (FCF) is addressed. Polyps coded as hyperplastic polyps (HP) from subjects with Lynch syndrome and FCF enrolled in the HNPCC-register at the Hvidovre University Hospital as well as adenomas from this population were retrieved and reviewed for features of SSP. Ninety-eight polyps coded as HP and 41...

Development of a DNA-Based Method for Distinguishing the Malaria Vectors, Anopheles gambiae From Anopheles arabiensis.

Science.gov (United States)

1986-06-01

our preliminary studies hybridization with the Droso- phila actin probe required such low stringency conditions that the signal to noise ratio made...Balabacensis complex of Southeast Asia (Diptera: Culicidae). Genetica 57:81-86. (14) Mahon RJ and PM Miethke. 1982. Anopheles farauti No. 3, a hitherto un

Endoscopic detection rate of sessile serrated lesions in Lynch syndrome patients is comparable with an age- and gender-matched control population: case-control study with expert pathology review.

Science.gov (United States)

Vleugels, Jasper L A; Sahin, Husna; Hazewinkel, Yark; Koens, Lianne; van den Berg, Jose G; van Leerdam, Monique E; Dekker, Evelien

2018-05-01

Carcinogenesis in Lynch syndrome involves fast progression of adenomas to colorectal cancer (CRC) because of microsatellite instability. The role of sessile serrated lesions (SSLs) and the serrated neoplasia pathway in these patients is unknown. The aim of this matched case-control study was to compare endoscopic detection rates and distribution of SSLs in Lynch syndrome patients with a matched control population. We collected data of Lynch syndrome patients with a proven germline mutation who underwent colonoscopy between January 2011 and April 2016 in 2 tertiary referral hospitals. Control subjects undergoing elective colonoscopy from 2011 and onward for symptoms or surveillance were selected from a prospectively collected database. Patients were matched 1:1 for age, gender, and index versus surveillance colonoscopy. An expert pathology review of serrated polyps was performed. The primary outcomes included the detection rates and distribution of SSLs. We identified 321 patients with Lynch syndrome who underwent at least 1 colonoscopy. Of these, 223 Lynch syndrome patients (mean age, 49.3; 59% women; index colonoscopy, 56%) were matched to 223 control subjects. SSLs were detected in 7.6% (95% confidence interval, 4.8-11.9) of colonoscopies performed in Lynch syndrome patients and in 6.7% (95% confidence interval, 4.1-10.8) of control subjects (P = .86). None of the detected SSLs in Lynch syndrome patients contained dysplasia. The detection rate of SSLs in Lynch syndrome patients undergoing colonoscopy is comparable with a matched population. These findings suggest that the role of the serrated neoplasia pathway in CRC development in Lynch syndrome seems to be comparable with that in the general population. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Indsigter og udfordringer i danske Lynch-syndrom-familier

DEFF Research Database (Denmark)

Therkildsen, Christina; Timshel, Susanne; Nilbert, Mef

2008-01-01

The Danish Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Register is a national resource that registers families with hereditary colorectal cancer. HNPCC is the most common type of hereditary colorectal cancer and carries an increased risk of other tumor types. Genetic diagnostics has...... identified 88 unique mutations in 164 Danish families delineated as Lynch syndrome families. Predictive genetic diagnostics enables the identification of high risk individuals, who are offered participation in surveillance programmes that effectively reduce morbidity and mortality in colorectal cancer....

Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients.

Science.gov (United States)

Jóri, Balazs; Kamps, Rick; Xanthoulea, Sofia; Delvoux, Bert; Blok, Marinus J; Van de Vijver, Koen K; de Koning, Bart; Oei, Felicia Trups; Tops, Carli M; Speel, Ernst Jm; Kruitwagen, Roy F; Gomez-Garcia, Encarna B; Romano, Andrea

2015-12-01

The risk to develop colorectal and endometrial cancers among subjects testing positive for a pathogenic Lynch syndrome mutation varies, making the risk prediction difficult. Genetic risk modifiers alter the risk conferred by inherited Lynch syndrome mutations, and their identification can improve genetic counseling. We aimed at identifying rare genetic modifiers of the risk of Lynch syndrome endometrial cancer. A family based approach was used to assess the presence of genetic risk modifiers among 35 Lynch syndrome mutation carriers having either a poor clinical phenotype (early age of endometrial cancer diagnosis or multiple cancers) or a neutral clinical phenotype. Putative genetic risk modifiers were identified by Next Generation Sequencing among a panel of 154 genes involved in endometrial physiology and carcinogenesis. A simple pipeline, based on an allele frequency lower than 0.001 and on predicted non-conservative amino-acid substitutions returned 54 variants that were considered putative risk modifiers. The presence of two or more risk modifying variants in women carrying a pathogenic Lynch syndrome mutation was associated with a poor clinical phenotype. A gene-panel is proposed that comprehends genes that can carry variants with putative modifying effects on the risk of Lynch syndrome endometrial cancer. Validation in further studies is warranted before considering the possible use of this tool in genetic counseling.

“Silencio”: hearing loss in David Lynch's Mulholland Drive

Directory of Open Access Journals (Sweden)

Allister Mactaggart

2014-11-01

Full Text Available In a filmmaking career replete with extraordinary images and sounds, David Lynch's Mulholland Drive (2001 stands out for attention as a striking and seemingly inexhaustible resource for analysis. In this article, this film is used to examine the specific ways in which Lynch uses pre-existing pop songs to wrap the spectator within the filmic soundscape. Nowhere is the complexity and uncanniness of pop music made more explicit than in Rebekah Del Rio's stunning performance of “Llorando (Crying” in the Club Silencio scene. The split between the singer's powerful performance and her subsequent collapse with the sound of the voice left hanging in the air marks a pivotal point in the film. This scene, coupled with other examples of feminine jouissance, is contrasted with the deadening roar of the master's voice, which solely demands obedience but is deaf to any reply. At the core of this article is an analysis of the status of the voice (and the gaze as examples of the Lacanian object a and its relationship to Marx's concept of surplus value. Mulholland Drive provides a powerful demonstration of how these concepts can be seen, heard, and felt in relation to film, and how sound can reverberate into the spaces and silences beyond the screen.

Paridade de Anopheles cruzii em Floresta Ombrófila Densa no Sul do Brasil Anopheles cruzii parity in dense rain forest in Southern Brazil

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Ana Caroline Dalla Bona

2006-12-01

Full Text Available OBJETIVO: Conhecer a paridade e desenvolvimento ovariano da espécie Anopheles cruzii, durante os períodos estacionais. MÉTODOS: As capturas foram realizadas quinzenalmente, no período matutino, de abril/2004 a abril/2005, no Parque Estadual do Palmito, município de Paranaguá litoral do Estado do Paraná. Mosquitos adultos foram capturados usando a técnica pouso homem. As dissecções foram feitas utilizando-se a técnica de Detinova e de Polovodova e a avaliação do desenvolvimento folicular, segundo os critérios de Christophers e Mer. RESULTADOS: Foram dissecadas 208 fêmeas de Anopheles cruzii. A maioria das fêmeas dissecadas nas estações eram nulíparas. Sendo que 14,4% eram nulíparas com folículo além do estádio II de Christophers & Mer, o que evidencia o exercício da hematofagia previamente à primeira oviposição. Observou-se que as populações de Anopheles cruzii são constituídas de indivíduos jovens, talvez em razão da alta mortalidade de fêmeas paridas. CONCLUSÕES: A provável discordância gonotrófica das fêmeas dissecadas é importante do ponto de vista epidemiológico, considerando que a fêmea pode procurar mais de um hospedeiro para completar a maturação dos seus ovos.OBJECTIVE: To determine the parity and ovarian development of Anopheles cruzii species during the seasons. METHODS: Collections were carried out fortnightly in the morning in the Palmito State Park in the municipality of Paranaguá, Southern Brazil, between April 2004 and April 2005. Adult mosquitoes were captured using human landing rate. Dissections were performed using Detinova's and Polovodova's methods and follicular development was assessed following Christophers and Mer's criteria. RESULTS: A total of 208 specimens of Anopheles cruzii were dissected. Most females dissected were nulliparous in the seasons; 14.4% of them were found to be nulliparous above Christophers and Mer's stage II, which shows previous blood meal prior to the

Seasonal abundance and blood feeding activity of Anopheles minimus Theobald (Diptera: Culicidae) in Thailand.

Science.gov (United States)

Chareonviriyaphap, Theeraphap; Prabaripai, Atchariya; Bangs, Michael J; Aum-Aung, Boonserm

2003-11-01

Anopheline mosquito larvae and adults were sampled at Ban Pu Teuy, Tri-Yok District, Kanchanaburi Province, western Thailand, from January 2000 to December 2001. Over the period of 2 yr, Anopheles minimus sensu lato was the most commonly collected species, followed by Anopheles swadiwongporni and Anopheles dirus sensu lato; all three species are important vectors of malaria in Thailand. Attempted blood feeding by An. minimus occurred throughout the night, with two distinct feeding peaks: strong activity immediately after sunset (1800-2100 hours), followed by a second, less pronounced, rise before sunrise (0300-0600 hours). Anopheles minimus were more abundant during the wet season compared with the dry and hot seasons, although nocturnal adult feeding patterns were similar. Anopheles minimus fed readily on humans inside and outside of houses, showing a slight preference for exophagy. The human-biting peak of An. minimus in our study area differed from other localities sampled in Thailand, indicating the possible existence of site-specific populations of An. minimus exhibiting different host-seeking behavior. These results underscore the importance of conducting site-specific studies to accurately determine vector larval habitats and adult activity patterns and linking their importance in malaria transmission in a given area.

The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome

DEFF Research Database (Denmark)

Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka

2008-01-01

Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention...

Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

Directory of Open Access Journals (Sweden)

Buchanan DD

2014-10-01

Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

Prospective Study of Combined Colon and Endometrial Cancer Screening in Women With Lynch Syndrome: A Patient-Centered Approach

Science.gov (United States)

Huang, Marilyn; Sun, Charlotte; Boyd-Rogers, Stephanie; Burzawa, Jennifer; Milbourne, Andrea; Keeler, Elizabeth; Yzquierdo, Rebecca; Lynch, Patrick; Peterson, Susan K.; Lu, Karen

2011-01-01

Background: Endometrial and colorectal cancers are the most common cancers in Lynch syndrome. Consensus guidelines recommend annual endometrial biopsy (EMB) and regular colonoscopies. We assessed the feasibility of concurrently performing EMB and colonoscopy and evaluated women's perception of pain, satisfaction, and acceptability. Methods: From July 2002 to December 2009, women who had a gene mutation for Lynch syndrome, met the Amsterdam II criteria, or had a high-risk situation that required screening were prospectively enrolled. After conscious sedation, the procedures were sequentially performed. Patients completed pre- and postprocedure questionnaires assessing pain, level of satisfaction, and acceptability. The Wilcoxon rank test and Mann-Whitney test were used to compare pain scores. Results: Forty-two women completed the study. Median age was 37 years (range, 25 to 73). Nineteen had previously had an EMB in the office setting. Women reported significantly lower median levels of pain in the combined procedure compared with previous office setting biopsies (P Lynch syndrome screening recommendations. PMID:21532810

History, genetics, and strategies for cancer prevention in Lynch syndrome.

Science.gov (United States)

Kastrinos, Fay; Stoffel, Elena M

2014-05-01

Colorectal cancer (CRC) is the most common gastrointestinal malignancy and the third cause of cancer death in men and women in the United States. The majority of CRC cases diagnosed annually are due to sporadic events, but up to 6% are attributed to known monogenic disorders that confer a markedly increased risk for the development of CRC and multiple extracolonic malignancies. Lynch syndrome is the most common inherited CRC syndrome and is associated with mutations in DNA mismatch repair genes, mainly MLH1 and MSH2 but also MSH6, PMS2, and EPCAM. Although the risk of CRC and endometrial cancer may approach near 75% and 50%, respectively, in gene mutation carriers, the identification of these individuals and at-risk family members through predictive genetic testing provides opportunities for cancer prevention including specialized cancer screening, intensified surveillance, and/or prophylactic surgeries. This article will provide a review of the major advances in risk assessment, molecular genetics, DNA mutational analyses, and cancer prevention and management made since Lynch syndrome was first described 100 years ago. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk

NARCIS (Netherlands)

Broeke, S.W. ten; Brohet, R.M.; Tops, C.M.; Klift, H.M. van der; Velthuizen, M.E.; Bernstein, I.; Capella Munar, G.; Garcia, E.; Hoogerbrugge, N.; Letteboer, T.G.; Menko, F.H.; Lindblom, A.; Mensenkamp, A.R.; Moller, P.; Os, T.A. van; Rahner, N.; Redeker, B.J.; Sijmons, R.H.; Spruijt, L.; Suerink, M.; Vos, Y.J.; Wagner, A.; Hes, F.J.; Vasen, H.F.A.; Nielsen, M.; Wijnen, J.T.

2015-01-01

PURPOSE: The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. METHODS: Data were collected from 98

RNF43 is mutated less frequently in Lynch Syndrome compared with sporadic microsatellite unstable colorectal cancers.

Science.gov (United States)

Fennell, Lochlan J; Clendenning, Mark; McKeone, Diane M; Jamieson, Saara H; Balachandran, Samanthy; Borowsky, Jennifer; Liu, John; Kawamata, Futoshi; Bond, Catherine E; Rosty, Christophe; Burge, Matthew E; Buchanan, Daniel D; Leggett, Barbara A; Whitehall, Vicki L J

2018-01-01

The WNT signaling pathway is commonly altered during colorectal cancer development. The E3 ubiquitin ligase, RNF43, negatively regulates the WNT signal through increased ubiquitination and subsequent degradation of the Frizzled receptor. RNF43 has recently been reported to harbor frequent truncating frameshift mutations in sporadic microsatellite unstable (MSI) colorectal cancers. This study assesses the relative frequency of RNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region of RNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, was BRAF wild type at V600E, were under 60 years of age at diagnosis, and demonstrated no promoter region methylation for MLH1 in tumor DNA. A validation cohort of 44 colorectal cancers from mismatch repair germline mutation carriers from the Australasian Colorectal Cancer Family Registry (ACCFR) were sequenced for the most common truncating mutation hotspots (X117 and X659). RNF43 mutations were found in 9 of 24 (37.5%) Lynch syndrome colorectal cancers. The majority of mutations were frameshift deletions in the G659 G7 repeat tract (29%); 2 cancers (2/24, 8%) from the one patient harbored frameshift mutations at codon R117 (C6 repeat tract) within exon 3. In the ACCFR validation cohort, RNF43 hotspot mutations were identified in 19/44 (43.2%) of samples, which was not significantly different to the initial series. The proportion of mutant RNF43 in Lynch syndrome related colorectal cancers is significantly lower than the previously reported mutation rate found in sporadic MSI colorectal cancers. These findings identify further genetic differences between sporadic and hereditary colorectal cancers. This may be because Lynch Syndrome cancers

Finding the needle in a haystack: identification of cases of Lynch syndrome with MLH1 epimutation.

Science.gov (United States)

Hitchins, Megan P

2016-07-01

Constitutional epimutation of the DNA mismatch repair gene, MLH1, represents a minor cause of Lynch syndrome. MLH1 epimutations are characterized by the soma-wide distribution of methylation of a single allele of the MLH1 promoter accompanied by constitutive allelic loss of transcription. 'Primary' MLH1 epimutations, considered pure epigenetic defects, tend to arise de novo in patients without a family history or any apparent genetic mutation. These demonstrate non-Mendelian inheritance. 'Secondary' MLH1 epimutations have a genetic basis and have been linked to non-coding genetic alterations in the vicinity of MLH1. These demonstrate autosomal dominant inheritance. Despite convincing evidence of their role in causing Lynch-type cancers, routine screening for MLH1 epimutations has not been widely adopted. Complicating factors may include: the need to perform additional methylation-based testing beyond the standard genetic screening for a germline mutation; the lack of a consensus algorithm for the selection of patients warranting MLH1 epimutation testing; overlapping molecular pathology features of MLH1 methylation and loss of MLH1 expression with more prevalent sporadic MSI cancers; the rarity of MLH1 epimutation; the variable inter-generational inheritance patterns; and the cost-effectiveness of screening. Nevertheless, a positive molecular diagnosis of MLH1 epimutation is clinically important because carriers have a high personal risk of developing metachronous Lynch-type cancers, and their relatives may also be at risk of carriage. Extending existing universal and clinic-based screening algorithms for Lynch syndrome to include an additional arm of selection criteria for cases warranting MLH1 epimutation testing could provide a cost-effective means of diagnosing these cases.

Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability.

Science.gov (United States)

Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide

2009-06-01

It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

Informing family members of individuals with Lynch syndrome: a guideline for clinical geneticists

NARCIS (Netherlands)

Menko, Fred H.; Aalfs, Cora M.; Henneman, Lidewij; Stol, Yrrah; Wijdenes, Miranda; Otten, Ellen; Ploegmakers, Marleen M. J.; Legemaate, Johan; Smets, Ellen M. A.; de Wert, Guido M. W. R.; Tibben, Aad

2013-01-01

The diagnosis of Lynch syndrome can lead to the prevention of colorectal cancer through periodic colonoscopies and removal of premalignant lesions in susceptible individuals. Therefore, predisposed individuals identified by mutation analysis are advised to inform their at-risk relatives about the

Informing family members of individuals with Lynch syndrome : a guideline for clinical geneticists

NARCIS (Netherlands)

Menko, Fred H.; Aalfs, Cora M.; Henneman, Lidewij; Stol, Yrrah; Wijdenes, Miranda; Otten, Ellen; Ploegmakers, Marleen M. J.; Legemaate, Johan; Smets, Ellen M. A.; de Wert, Guido M. W. R.; Tibben, Aad

The diagnosis of Lynch syndrome can lead to the prevention of colorectal cancer through periodic colonoscopies and removal of premalignant lesions in susceptible individuals. Therefore, predisposed individuals identified by mutation analysis are advised to inform their at-risk relatives about the

1 SHORT COMMUNICATION Resting behaviour of Anopheles ...

African Journals Online (AJOL)

2011-10-04

Oct 4, 2011 ... Resting behaviour of Anopheles gambiae s.l. and its implication on malaria .... nature) were requested to sleep under the double mosquito net trap (one ... designed from the DNA sequences of the intergenic spacer region of ...

Identification of Spiroplasma insolitum symbionts in Anopheles gambiae [version 1; referees: 2 approved, 1 not approved

Directory of Open Access Journals (Sweden)

Sharon T. Chepkemoi

2017-09-01

Full Text Available Background: Insect symbionts have the potential to block the transmission of vector-borne diseases by their hosts. The advancement of a symbiont-based transmission blocking strategy for malaria requires the identification and study of Anopheles symbionts. Methods: High throughput 16S amplicon sequencing was used to profile the bacteria associated with Anopheles gambiae sensu lato and identify potential symbionts. The polymerase chain reaction (PCR with specific primers were subsequently used to monitor symbiont prevalence in field populations, as well as symbiont transmission patterns. Results: We report the discovery of the bacterial symbiont, Spiroplasma, in Anopheles gambiae in Kenya. We determine that geographically dispersed Anopheles gambiae populations in Kenya are infected with Spiroplasma at low prevalence levels. Molecular phylogenetics indicates that this Anopheles gambiae associated Spiroplasma is a member of the insolitum clade. We demonstrate that this symbiont is stably maternally transmitted across at least two generations and does not significantly affect the fecundity or egg to adult survival of its host. Conclusions: In diverse insect species, Spiroplasma has been found to render their host resistant to infection by pathogens. The identification of a maternally transmitted strain of Spiroplasma in Anopheles gambiae may therefore open new lines of investigation for the development of symbiont-based strategies for blocking malaria transmission.

Comparative Studies on the Stenogamous and Eurygamous Behavior of Eight Anopheles Species of the Hyrcanus Group (Diptera: Culicidae in Thailand

Directory of Open Access Journals (Sweden)

Adulsak Wijit

2016-03-01

Full Text Available Establishment of laboratory colony is essential for mosquito-borne-disease research. Mating behavior of stenogamous Anopheles peditaeniatus and seven eurygamous species (Anopheles argyropus, Anopheles crawfordi, Anopheles nigerrimus, Anopheles nitidus, Anopheles paraliae (=An. lesteri, Anopheles pursati and Anopheles sinensis, were investigated and compared in this study. The self-mating success of adult mosquitoes in different size cages at two density resting surface (DRS values, 3.6 and 7.2, was statistically significant between stenogamous and eurygamous species. The results obtained from comparative measurements of specific characters in adult females (maxillary palpomere and antennal sensilla characters and males (wing and genitalia indicate those characters might influence the mating success of An. peditaeniatus in a small cage. The gonostylus of An. peditaeniatus was shorter than the eurygamous species. Additionally, the lower frequency of clasper movement and shorter mating time could be important mechanisms that control the stenogamous behavior of An. peditaeniatus. Interestingly, for the first time, a cluster of large sensilla coeloconica was recorded on the antenna of An. argyropus and An. peditaeniatus females. There was no statistically significant difference in the mean number per female of those large antennal sensilla coeloconica among six of the eurygamous species.

Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk

NARCIS (Netherlands)

ten Broeke, Sanne W.; Brohet, Richard M.; Tops, Carli M.; van der Klift, Heleen M.; Velthuizen, Mary E.; Bernstein, Inge; Capellá Munar, Gabriel; Gomez Garcia, Encarna; Hoogerbrugge, Nicoline; Letteboer, Tom G. W.; Menko, Fred H.; Lindblom, Annika; Mensenkamp, Arjen R.; Moller, Pal; van Os, Theo A.; Rahner, Nils; Redeker, Bert J. W.; Sijmons, Rolf H.; Spruijt, Liesbeth; Suerink, Manon; Vos, Yvonne J.; Wagner, Anja; Hes, Frederik J.; Vasen, Hans F.; Nielsen, Maartje; Wijnen, Juul T.

2015-01-01

Purpose The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Methods Data were collected from 98 PMS2

Lynch Syndrome Caused by Germline PMS2 Mutations : Delineating the Cancer Risk

NARCIS (Netherlands)

ten Broeke, Sanne W.; Brohet, Richard M.; Tops, Carli M.; van der Klift, Heleen M.; Velthuizen, Mary E.; Bernstein, Inge; Capella Munar, Gabriel; Garcia, Encarna Gomez; Hoogerbrugge, Nicoline; Letteboer, Tom G. W.; Menko, Fred H.; Lindblom, Annika; Mensenkamp, Arjen R.; Moller, Pal; Van Os, Theo A.; Rahner, Nils; Redeker, Bert J. W.; Sijmons, Rolf H.; Spruijt, Liesbeth; Suerink, Manon; Vos, Yvonne J.; Wagner, Anja; Hes, Frederik J.; Vasen, Hans F.; Nielsen, Maartje; Wijnen, Juul T.

2015-01-01

Purpose The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Methods Data were collected from 98 PMS2

Efficacy of b-lynch brace suture in postpartum haemorrhage

International Nuclear Information System (INIS)

Tarique, S.; Wazir, S.; Moeen, G.

2011-01-01

Massive uncontrolled haemorrhage after childbirth is the leading cause of maternal death in developing countries. Postpartum haemorrhage is traditionally defined as blood loss of more than 500 ml after vaginal delivery and more than 1000 ml after caesarean section, but intraoperative estimation of blood loss is inaccurate. Uterine atony alone accounts for 75 - 90% of PPH. To estimate the effectiveness and safety of B-Lynch brace Suture in the management of primary postpartum haemorrhage (PPH). (author)

Cryptic species Anopheles daciae (Diptera: Culicidae) found in the Czech Republic and Slovakia.

Science.gov (United States)

Blažejová, Hana; Šebesta, Oldřich; Rettich, František; Mendel, Jan; Čabanová, Viktória; Miterpáková, Martina; Betášová, Lenka; Peško, Juraj; Hubálek, Zdeněk; Kampen, Helge; Rudolf, Ivo

2018-01-01

We report the distribution of mosquitoes of the maculipennis complex in two distinct areas of the Czech Republic (Bohemia and South Moravia) and in one locality of neighbouring Slovakia with emphasis on the detection of the newly described cryptic species Anopheles daciae (Linton, Nicolescu & Harbach, 2004). A total of 691 mosquitoes were analysed using a species-specific multiplex PCR assay to differentiate between the members of the maculipennis complex. In the Czech Republic, we found Anopheles maculipennis (with a prevalence rate of 1.4%), Anopheles messeae (49.0%) and Anopheles daciae (49.6%). In Slovakia, only An. messeae (52.1%) and An. daciae (47.9%) were detected. In this study, An. daciae was documented for the first time in the two countries where it represented a markedly higher proportion of maculipennis complex species (with an overall prevalence almost reaching 50%) in comparison to previous reports from Germany, Romania and Poland. The determination of the differential distribution of maculipennis complex species will contribute to assessing risks of mosquito-borne diseases such as malaria or dirofilariasis.

Brachiola gambiae sp n. the microsporidian parasite of Anopheles gambiae and A-melas in Liberia

Czech Academy of Sciences Publication Activity Database

Weiser, Jaroslav; Žižka, Zdeněk

2004-01-01

Roč. 43, č. 1 (2004), s. 73-80 ISSN 0065-1583 Institutional research plan: CEZ:AV0Z5007907 Keywords : Anopheles gambiae * Anopheles melas * Brachiola gambiae Subject RIV: EG - Zoology Impact factor: 0.986, year: 2004

Diagnostic Strategies for Early Lynch Syndrome Detection: From Molecular Testing to Economic Evaluation

NARCIS (Netherlands)

C.H.M. Leenen (Celine)

2015-01-01

markdownabstract__Abstract__ Lynch syndrome (LS) is an autosomal dominant inherited syndrome that predisposes to multiple malignancies, in particular colorectal cancer (CRC) and endometrial cancer (EC). The lifetime risk of developing CRC for a LS mutation carrier is 25 to 70%, while women

Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy

NARCIS (Netherlands)

Haanstra, Jasmijn F.; Al-Toma, Abdul; Dekker, Evelien; Vanhoutvin, Steven A. L. W.; Nagengast, Fokko M.; Mathus-Vliegen, Elisabeth M.; van Leerdam, Monique E.; Cappel, Wouter H. de Vos tot Nederveen; Sanduleanu, Silvia; Veenendaal, Roeland A.; Cats, Annemieke; Vasen, Hans F. A.; Kleibeuker, Jan H.; Koornstra, Jan J.

2015-01-01

Objective The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). Design After obtaining informed consent, asymptomatic proven gene mutation carriers aged 3570 years were included in this prospective

Exploring clinicians' attitudes about using aspirin for risk reduction in people with Lynch Syndrome with no personal diagnosis of colorectal cancer.

Science.gov (United States)

Chen, Yanni; Peate, Michelle; Kaur, Rajneesh; Meiser, Bettina; Wong, Tim; Kirk, Judy; Ward, Robyn L; Goodwin, Annabel; Macrae, Finlay; Hiller, Janet; Trainer, Alison H; Mitchell, Gillian

2017-01-01

Recent research has shown that aspirin reduces the risk of cancers associated with Lynch Syndrome. However, uncertainty exists around the optimal dosage, treatment duration and whether the benefits of aspirin as a risk-reducing medication (RRM) outweigh adverse medication related side-effects. Little is known about clinicians' attitudes, current practice, and perceived barriers to recommending aspirin as a RRM. To explore the attitudes of clinicians who discuss risk management options with patients with Lynch Syndrome towards using aspirin as a RRM. Clinicians were invited through professional organisations to complete an online survey. Topics included their clinical experience with Lynch Syndrome, views and practice of recommending aspirin as a RRM, and knowledge about clinical risk management guidelines for Lynch Syndrome. Comparison of attitudes was made between three professional groups. 181 respondents were included in the analysis: 59 genetics professionals (genetic counsellors and clinical geneticists, medical oncologists with specialist training in familial cancer), 49 gastroenterologists and 73 colorectal surgeons. Most clinicians (76 %) considered aspirin to be an effective RRM and most (72 %) were confident about discussing it. In all professional categories, those who were confident about discussing aspirin with patients perceived it to be an effective RRM (OR = 2.8 [95 % CI = 1.8-4.2], p Lynch Syndrome patients compared to 69 % of gastroenterologists and 68 % of colorectal surgeons. Those who considered aspirin as an effective RRM or who felt confident in their knowledge of the aspirin literature were more likely (OR = 10 [95 % CI = 1.5-65], p = 0.010, OR = 6 [95 % CI = 2.2-16], p Lynch Syndrome per year were more likely to be confident in their knowledge of the aspirin literature and discussing it with patients (OR = 4.1 [95 % CI = 1.6-10.2], p = 0.003). Explicit recommendations to take aspirin, was reported by 65

Blood-feeding patterns of Anopheles mosquitoes in a malaria-endemic area of Bangladesh

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Bashar Kabirul

2012-02-01

Full Text Available Abstract Background Blood-feeding patterns of mosquitoes are crucial for incriminating malaria vectors. However, little information is available on the host preferences of Anopheles mosquitoes in Bangladesh. Therefore, the objective of the present study was to determine the hematophagic tendencies of the anophelines inhabiting a malaria-endemic area of Bangladesh. Methods Adult Anopheles mosquitoes were collected using light traps (LTs, pyrethrum spray (PS, and human bait (HB from a malaria-endemic village (Kumari, Bandarban, Bangladesh during the peak months of malaria transmission (August-September. Enzyme-linked immunosorbent assay (ELISA and polymerase chain reaction (PCR were performed to identify the host blood meals of Anopheles mosquitoes. Results In total, 2456 female anopheline mosquitoes representing 21 species were collected from the study area. Anopheles vagus Doenitz (35.71% was the dominant species followed by An. philippinensis Ludlow (26.67% and An. minimus s.l. Theobald (5.78%. All species were collected by LTs set indoors (n = 1094, 19 species were from outdoors (n = 784, whereas, six by PS (n = 549 and four species by HB (n = 29. Anopheline species composition significantly differed between every possible combination of the three collection methods (χ2 test, P Anopheles samples belonging to 17 species. Values of the human blood index (HBI of anophelines collected from indoors and outdoors were 6.96% and 11.73%, respectively. The highest values of HBI were found in An. baimai Baimaii (80%, followed by An. minimus s.l. (43.64% and An. annularis Van den Wulp (37.50%. Anopheles baimai (Bi = 0.63 and An. minimus s.l. (Bi = 0.24 showed strong relative preferences (Bi for humans among all hosts (human, bovine, goats/sheep, and others. Anopheles annularis, An. maculatus s.l. Theobald, and An. pallidus Theobald exhibited opportunistic blood-feeding behavior, in that they fed on either humans or animals, depending on whichever was

Haematuria in association with Lynch syndrome

Directory of Open Access Journals (Sweden)

Marwan Ma'ayeh

2012-04-01

Full Text Available A 40-year-old Caucasian male presented to the Emergency Department complaining of intermittent painless frank haematuria. Past medical history was significant for Hereditary Non-Polyposis Colon Cancer (HNPCC and a prophylactic total colectomy. Computed tomography urogram showed thickening in the posterior wall of the bladder. Cystoscopy showed a small bladder mass. Histology showed a papillary urothelial neoplasm of low malignant potential. HNPCC, also known as Lynch Syndrome, is an autosomal dominant disorder responsible for 3-5% of colorectal cancers. There are certain cancers known to be associated with HNPCC; colorectal cancer, endometrial, ovarian, stomach, pancreas, biliary tract, small bowel, brain, renal pelvic and ureteric tumours, sebaceous gland adenomas and keratocanthomas. An association with bladder tumours is not well established.

Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance

DEFF Research Database (Denmark)

Møller, Pål; Seppälä, Toni; Bernstein, Inge

2017-01-01

study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene. RESULTS: 1942 mutation carriers without previous...... carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24......%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian. CONCLUSIONS: The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite...

SNP association study in PMS2-associated Lynch syndrome.

Science.gov (United States)

Ten Broeke, Sanne W; Elsayed, Fadwa A; Pagan, Lisa; Olderode-Berends, Maran J W; Garcia, Encarna Gomez; Gille, Hans J P; van Hest, Liselot P; Letteboer, Tom G W; van der Kolk, Lizet E; Mensenkamp, Arjen R; van Os, Theo A; Spruijt, Liesbeth; Redeker, Bert J W; Suerink, Manon; Vos, Yvonne J; Wagner, Anja; Wijnen, Juul T; Steyerberg, E W; Tops, Carli M J; van Wezel, Tom; Nielsen, Maartje

2017-11-17

Lynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly on MLH1, MSH2 and MSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs in PMS2 mutation carriers. A cohort study was performed in 507 PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. Discrimination was assessed with a concordance statistic in a bootstrap cross-validation procedure. Individual SNPs only had non-significant associations with CRC occurrence with HRs lower than 2, although male carriers of allele A at rs1321311 (6p21.31) may have increased risk of CRC (HR = 2.1, 95% CI 1.2-3.0). A polygenic risk score (PRS) based on 24 HRs had an HR of 2.6 (95% CI 1.5-4.6) for the highest compared to the lowest quartile, but had no discriminative ability (c statistic 0.52). Previously suggested SNPs do not modify CRC risk in PMS2 carriers. Future large studies are needed for improved risk stratification among Lynch syndrome patients.

Lynch syndrome in South America: past, present and future.

Science.gov (United States)

Vaccaro, Carlos A; Sarroca, Carlos; Rossi, Benedito; Lopez-Kostner, Francisco; Dominguez, Mev; Calo, Natalia Causada; Cutait, Raul; Valle, Adriana Della; Nuñez, Lina; Neffa, Florencia; Alvarez, Karin; Gonzalez, Maria Laura; Kalfayan, Pablo; Lynch, Henry T; Church, James

2016-07-01

After decades of unawareness about Lynch syndrome, the medical community in South America is increasingly interested and informed. The visits and support of mentors like H. T. Lynch had been crucial to this awakening. Several countries have at least one registry with skilled personnel in genetic counseling and research. However, this only represents a very restricted resource for the region. According to the GETH, there are 27 hereditary cancer care centers in South America (21 in Brazil, 3 in Argentina, 1 in Uruguay, 1 in Chile and 1 in Peru). These registries differ in fundamental aspects of function, capabilities and funding, but are able to conduct high quality clinical, research and educational activities due to the dedication and personal effort of their members, and organizational support. More support from the governments as well as the participation of the community would boost the initiatives of people leading these groups. Meantime, the collaboration among the South American registries and the involvement of registries and leaders from developed countries will allow to maximize the efficiency in caring for affected patients and their families. The aim of this article is to describe how the knowledge of LS began to be spread in South America, how the first registries were organized and to summarize the current state of progress. In addition, we will provide an update of the clinical and molecular findings in the region.

Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy

NARCIS (Netherlands)

Haanstra, Jasmijn F.; Al-Toma, Abdul; Dekker, Evelien; Vanhoutvin, Steven A. L. W.; Nagengast, Fokko M.; Mathus-Vliegen, Elisabeth M.; van Leerdam, Monique E.; de Vos tot Nederveen Cappel, Wouter H.; Sanduleanu, Silvia; Veenendaal, Roeland A.; Cats, Annemieke; Vasen, Hans F. A.; Kleibeuker, Jan H.; Koornstra, Jan J.

2015-01-01

The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). After obtaining informed consent, asymptomatic proven gene mutation carriers aged 35-70 years were included in this prospective multicentre study in

A novel deletion in the splice donor site of MLH1 exon 6 in a Japanese colon cancer patient with Lynch syndrome.

Science.gov (United States)

Yamaguchi, Junya; Sato, Yuri; Kita, Mizuho; Nomura, Sachio; Yamamoto, Noriko; Kato, Yo; Ishikawa, Yuichi; Arai, Masami

2015-10-01

Lynch syndrome is an autosomal dominantly inherited disease that is characterized by a predisposition to cancers, mainly colorectal cancer. Germline mutations of DNA mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2 have been described in patients with Lynch syndrome. Here, we report deletion of 2 bp in the splice donor site of the MLH1 exon 6 (c.545+4_545+5delCA) in a 48-year-old Japanese woman with Lynch syndrome. RT-PCR direct sequencing analysis revealed that this mutation led to an increase in the level of an MLH1 transcript in which exon 6 was skipped, and may cause a frameshift (p.E153FfsX8). Therefore, this mutation appears to be pathogenic and is responsible for Lynch syndrome. Additionally, analysis of the patient's tumor cells indicated microsatellite instability high phenotype and loss of the MLH1 and PMS2 proteins. To our knowledge, this is a germline splice site mutation of MLH1 that has not been reported previously. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of a rare variant (c.2635-2A>G) of the MSH2 gene in a family with Lynch syndrome.

Science.gov (United States)

Cariola, Filomena; Disciglio, Vittoria; Valentini, Anna M; Lotesoriere, Claudio; Fasano, Candida; Forte, Giovanna; Russo, Luciana; Di Carlo, Antonio; Guglielmi, Floranna; Manghisi, Andrea; Lolli, Ivan; Caruso, Maria L; Simone, Cristiano

2018-04-01

Lynch syndrome is caused by germline mutations in one of the mismatch repair genes ( MLH1, MSH2, MSH6, and PMS2) or in the EPCAM gene. Lynch syndrome is defined on the basis of clinical, pathological, and genetic findings. Accordingly, the identification of predisposing genes allows for accurate risk assessment and tailored screening protocols. Here, we report a family case with three family members manifesting the Lynch syndrome phenotype, all of which harbor the rare variant c.2635-2A>G affecting the splice site consensus sequence of intron 15 of the MSH2 gene. This mutation was previously described only in one family with Lynch syndrome, in which mismatch repair protein expression in tumor tissues was not assessed. In this study, we report for the first time the molecular characterization of the MSH2 c.2635-2A>G variant through in silico prediction analysis, microsatellite instability, and mismatch repair protein expression experiments on tumor tissues of Lynch syndrome patients. The potential effect of the splice site variant was revealed by three splicing prediction bioinformatics tools, which suggested the generation of a new cryptic splicing site. The potential pathogenic role of this variant was also revealed by the presence of microsatellite instability and the absence of MSH2/MSH6 heterodimer protein expression in the tumor cells of cancer tissues of the affected family members. We provide compelling evidence in favor of the pathogenic role of the MSH2 variant c.2635-2A>G, which could induce an alteration of the canonical splice site and consequently an aberrant form of the protein product (MSH2).

Radiation induced reciprocal translocations and inversions in anopheles albimanus

International Nuclear Information System (INIS)

Kaiser, P.E.; Seawright, J.A.; Benedict, M.Q.; Narang, S.

1982-01-01

Reciprocal translocations and inversions were induced in Anopheles albimanus Wiedemann by irradiation of males with X rays. A total of 1669 sperm were assayed, and 175 new aberrations were identified as follows: 102 reciprocal translocations (67 autosomal and 35 sex-linked), 45 pericentric inversions, and 28 paracentric inversions. Eleven of the translocations were nearly whole-arm interchanges, and these were selected for the construction of 'capture systems' for compound chromosomes. Two double-heterozygous translocation strains and four homozygous translocation strains were established. Anopheles albimanus females were irradiated, and a pseudolinkage scheme involving mutant markers was employed to identify reciprocal translocations. The irradiation of females was very inefficient; only one translocation was recovered from 1080 ova tested

Molecular identification of Anopheles gambiae sensu stricto Giles ...

African Journals Online (AJOL)

User

2016-09-28

Sep 28, 2016 ... responsible for the transmission. The knowledge of which form, Anopheles coluzzii, A. .... National Council for Science and Technology and Health Research ..... Styer ML, Carey RJ, Wang JL, Scott TW (2007). Mosquitoes Do.

Gene variants of unknown clinical significance in Lynch syndrome. An introduction for clinicians

NARCIS (Netherlands)

Sijmons, Rolf H.; Greenblatt, Marc S.; Genuardi, Maurizio

Clinicians referring patients for genetic testing for Lynch syndrome will sooner or later receive results for DNA Mismatch Repair (MMR) genes reporting DNA changes that are unclear from a clinical point of view. These changes are referred to as variants of unknown, or unclear, clinical significance

A rare case of choroid plexus carcinoma that led to the diagnosis of Lynch syndrome (hereditary nonpolyposis colorectal cancer).

Science.gov (United States)

Zhu, Viola W; Hinduja, Sanjay; Knezevich, Stevan R; Silveira, William R; DeLozier, Celia D

2017-07-01

Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder characterized by a significant risk of colorectal and endometrial cancers. A variety of other epithelial cancers may be associated with this syndrome. Brian tumors are infrequent, but have been reported in series. Here, we report a case of a 34-year-old Caucasian woman with WHO grade III choroid plexus carcinoma (CPC). Comprehensive genomic profiling of the patient's resected brain tumor revealed mutations in six genes: PTEN, VHL, MSH6, NOTCH1, RB1, and TP53. Family history is significant for endometrial cancer in her mother and sister as well as colon cancer in her maternal grandfather suggestive of Lynch syndrome. Site-specific mutational analysis showed the MSH6 mutation (p.R482*) in peripheral lymphocytes. Subsequently we performed immunohistochemical staining of the tumor tissue which demonstrated widespread loss of MSH6 with intact MSH2, MLH1, and PMS2. The diagnosis of Lynch syndrome due to a mutation in MSH6 was therefore established. Our patient elected to have adjuvant radiation to the surgical bed only followed by prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy and is doing very well. To our knowledge, this is the first case report of CPC in an adult patient with a germline MSH6 mutation. We believe our data have provided molecular evidence to suggest that CPC could potentially be part of the Lynch syndrome spectrum. Published by Elsevier B.V.

Distribution and infectivity of anopheles mosquitoes and ...

African Journals Online (AJOL)

Malaria still remains a major public health problem in Nigeria, despite serious efforts to lessen its adverse impact. A malaria survey was conducted to determine the distribution and infectivity rate of Anopheles species, and asymptomatic malaria infections in Gboko. Mosquitoes were collected at selected sites, using ...

Association of Mismatch Repair Mutation With Age at Cancer Onset in Lynch Syndrome: Implications for Stratified Surveillance Strategies.

Science.gov (United States)

Ryan, Neil A J; Morris, Julie; Green, Kate; Lalloo, Fiona; Woodward, Emma R; Hill, James; Crosbie, Emma J; Evans, D Gareth

2017-12-01

Lynch syndrome is caused by dominantly inherited germline mutations that predispose individuals to colorectal, endometrial, ovarian, and other cancers through inactivation of the cellular mismatch repair system. Lynch syndrome–associated cancers are amenable to surveillance strategies that may improve survival. The age at which surveillance should start is disputed. To determine whether mutated gene and type of mutation influence age at onset of Lynch syndrome–associated cancers. A retrospective cohort study of individuals with Lynch syndrome–associated colorectal, endometrial, and/or ovarian cancers whose medical records were included in the clinical database of a large quaternary referral center for genomic medicine in the Northwest of England. Mutated gene (MLH1, MSH2, MSH6, and/or PMS2) and type of mutation (truncating, splicing, or large rearrangement). Age at cancer diagnosis. A total of 1063 individuals with proven Lynch syndrome were included, 495 male and 568 female (mean age 52 years; age range, 10-93 years [children were included in the database, but no children developed cancer]). There were 546 men and women with colorectal cancer, 162 women with endometrial cancer, and 49 women with ovarian cancer; mean follow-up was 68.2 months. Among MLH1 mutation carriers, mutations in MLH1 were associated with colorectal cancer in 249 (61%) of 409 men and women; endometrial cancer in 53 of 196 (27%) women; and ovarian cancer in 15 (8%) of 196 women. Among MSH2 mutation carriers, mutations in MSH2 (the most prevalent mutations overall) were most commonly associated with female-specific cancers: endometrial cancer in 83 (30%) of 279 women; ovarian cancer in 28 (10%) of 279 women; and colorectal cancer in 239 (50%) 479 men and women. Mutations in MSH6 were less prevalent, and MSH6 mutation carriers presented with colorectal and endometrial cancer at later ages than carriers of mutations in MSH2 or MLH1. When stratified by mutation type, women with truncating

Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome.

Science.gov (United States)

Salo-Mullen, Erin E; Lynn, Patricio B; Wang, Lu; Walsh, Michael; Gopalan, Anuradha; Shia, Jinru; Tran, Christina; Man, Fung Ying; McBride, Sean; Schattner, Mark; Zhang, Liying; Weiser, Martin R; Stadler, Zsofia K

2018-01-01

Lynch syndrome is an autosomal dominant condition caused by pathogenic mutations in the DNA mismatch repair (MMR) genes. Although commonly associated with clinical features such as intellectual disability and congenital anomalies, contiguous gene deletions may also result in cancer predisposition syndromes. We report on a 52-year-old male with Lynch syndrome caused by deletion of chromosome 2p16.3-p21. The patient had intellectual disability and presented with a prostatic adenocarcinoma with an incidentally identified synchronous sigmoid adenocarcinoma that exhibited deficient MMR with an absence of MSH2 and MSH6 protein expression. Family history was unrevealing. Physical exam revealed short stature, brachycephaly with a narrow forehead and short philtrum, brachydactyly of the hands, palmar transverse crease, broad and small feet with hyperpigmentation of the soles. The patient underwent total colectomy with ileorectal anastomosis for a pT3N1 sigmoid adenocarcinoma. Germline genetic testing of the MSH2, MSH6, and EPCAM genes revealed full gene deletions. SNP-array based DNA copy number analysis identified a deletion of 4.8 Mb at 2p16.3-p21. In addition to the three Lynch syndrome associated genes, the deleted chromosomal section encompassed genes including NRXN1, CRIPT, CALM2, FBXO11, LHCGR, MCFD2, TTC7A, EPAS1, PRKCE, and 15 others. Contiguous gene deletions have been described in other inherited cancer predisposition syndromes, such as Familial Adenomatous Polyposis. Our report and review of the literature suggests that contiguous gene deletion within the 2p16-p21 chromosomal region is a rare cause of Lynch syndrome, but presents with distinct phenotypic features, highlighting the need for recognition and awareness of this syndromic entity.

Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations

Directory of Open Access Journals (Sweden)

Bartuma Katarina

2012-05-01

Full Text Available Abstract Background A growing number of individuals are diagnosed with hereditary cancer. Though increased levels of anxiety and depression have been demonstrated around the time of genetic counselling, most individuals handle life at increased risk well. Data have, however, been collected on individual basis, which led us to focus on family perspectives of hereditary cancer. Methods Lynch syndrome represents a major type of hereditary colorectal and gynaecological cancer. We preformed open-ended interviews with 27 informants from 9 Lynch syndrome families. Inductive content analysis revealed three major themes: transition to a risk family, patterns of communication and influence on family relations and individual roles. Results Family members described how learning about Lynch syndrome shifted focus from daily issues to concerns about cancer. Changes in communication related to difficulties in talking to children about heredity and informing new family members and distant relatives about an increased risk of cancer. Influence on relations was exemplified by family members taking on different roles, e.g. females often being responsible for coordinating information about heredity and providing support. Families in which members had experienced cancer at young age typically informed children soon after learning about heredity and at young age, whereas families with experience of cancer at higher age postponed information and thereby also genetic counselling. Conclusions Three major family perspectives are described in Lynch syndrome families; becoming a risk family, patterns of communication and influence on family relations. Since these issues are central, our findings suggests that such family perspectives should be considered during genetic counselling in order to contribute to information spread, help family members cope with the increased risk, and motivate family members at risk to undergo surveillance.

Identification of field caught Anopheles gambiae s.s. and Anopheles arabiensis by TaqMan single nucleotide polymorphism genotyping

Directory of Open Access Journals (Sweden)

Bayoh Nabie M

2007-02-01

Full Text Available Abstract Background Identification of Anopheles gambiae s.s. and Anopheles arabiensis from field-collected Anopheles gambiae s.l. is often necessary in basic and applied research, and in operational control programmes. The currently accepted method involves use of standard polymerase chain reaction amplification of ribosomal DNA (rDNA from the 3' 28S to 5' intergenic spacer region of the genome, and visual confirmation of amplicons of predicted size on agarose gels, after electrophoresis. This report describes development and evaluation of an automated, quantitative PCR method based upon TaqMan™ single nucleotide polymorphism (SNP genotyping. Methods Standard PCR, and TaqMan SNP genotyping with newly designed primers and fluorophore-labeled probes hybridizing to sequences of complementary rDNA specific for either An. gambiae s.s. or An. arabiensis, were conducted in three experiments involving field-collected An. gambiae s.l. from western Kenya, and defined laboratory strains. DNA extraction was from a single leg, sonicated for five minutes in buffer in wells of 96-well PCR plates. Results TaqMan SNP genotyping showed a reaction success rate, sensitivity, and species specificity comparable to that of standard PCR. In an extensive field study, only 29 of 3,041 (0.95% were determined to be hybrids by TaqMan (i.e., having rDNA sequences from both species, however, all but one were An. arabiensis by standard PCR, suggesting an acceptably low (ca. 1% error rate for TaqMan genotyping in mistakenly identifying species hybrids. Conclusion TaqMan SNP genotyping proved to be a sensitive and rapid method for identification of An. gambiae s.l. and An. arabiensis, with a high success rate, specific results, and congruence with the standard PCR method.

Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch syndrome.

Science.gov (United States)

Morak, Monika; Koehler, Udo; Schackert, Hans Konrad; Steinke, Verena; Royer-Pokora, Brigitte; Schulmann, Karsten; Kloor, Matthias; Höchter, Wilhelm; Weingart, Josef; Keiling, Cortina; Massdorf, Trisari; Holinski-Feder, Elke

2011-08-01

A positive family history, germline mutations in DNA mismatch repair genes, tumours with high microsatellite instability, and loss of mismatch repair protein expression are the hallmarks of hereditary non-polyposis colorectal cancer (Lynch syndrome). However, in ~10-15% of cases of suspected Lynch syndrome, no disease-causing mechanism can be detected. Oligo array analysis was performed to search for genomic imbalances in patients with suspected mutation-negative Lynch syndrome with MLH1 deficiency in their colorectal tumours. A deletion in the LRRFIP2 (leucine-rich repeat flightless-interacting protein 2) gene flanking the MLH1 gene was detected, which turned out to be a paracentric inversion on chromosome 3p22.2 creating two new stable fusion transcripts between MLH1 and LRRFIP2. A single-nucleotide polymorphism in MLH1 exon 8 was expressed from both alleles, initially pointing to appropriate MLH1 function at least in peripheral cells. In a second case, an inherited duplication of the MLH1 gene region resulted in constitutional MLH1 promoter methylation. Constitutional MLH1 promoter methylation may therefore in rare cases be a heritable disease mechanism and should not be overlooked in seemingly sporadic patients.

Increasing awareness and knowledge of lifestyle recommendations for cancer prevention in Lynch syndrome carriers

NARCIS (Netherlands)

Vrieling, A.; Visser, A.; Hoedjes, Meeke; Hurks, H.M.H.; Gómez García, E.; Hoogerbrugge, N.; Kampman, E.

2018-01-01

Lynch syndrome (LS) mutation carriers may reduce their cancer risk by adhering to lifestyle recommendations for cancer prevention. This study tested the effect of providing LS mutation carriers with World Cancer Research Fund-the Netherlands (WCRF-NL) health promotion materials on awareness and

Lynch syndrome patients' views of and preferences for return of results following whole exome sequencing.

Science.gov (United States)

Hitch, Kelly; Joseph, Galen; Guiltinan, Jenna; Kianmahd, Jessica; Youngblom, Janey; Blanco, Amie

2014-08-01

Whole exome sequencing (WES) uses next generation sequencing technology to provide information on nearly all functional, protein-coding regions in an individual's genome. Due to the vast amount of information and incidental findings that can be generated from this technology, patient preferences must be investigated to help clinicians consent and return results to patients. Patients (n = 19) who were previously clinically diagnosed with Lynch syndrome, but received uninformative negative Lynch syndrome genetic results through traditional molecular testing methods participated in semi-structured interviews after WES testing but before return of results to explore their views of WES and preferences for return of results. Analyses of interview results found that nearly all participants believed that the benefits of receiving all possible results generated from WES outweighed the undesirable effects. The majority of participants conveyed that relative to coping with a cancer diagnosis, information generated from WES would be manageable. Importantly, participants' experience with Lynch syndrome influenced their notions of genetic determinism, tolerance for uncertain results, and family communication plans. Participants would prefer to receive WES results in person from a genetic counselor or medical geneticist so that an expert could help explain the meaning and implications of the potentially large quantity and range of complicated results. These results underscore the need to study various populations with regard to the clinical use of WES in order to effectively and empathetically communicate the possible implications of this new technology and return results.

Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence?

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Lobo, João; Pinto, Carla; Freitas, Micaela; Pinheiro, Manuela; Vizcaino, Rámon; Oliva, Esther; Teixeira, Manuel R; Jerónimo, Carmen; Bartosch, Carla

2017-03-01

Currently, uveal melanoma is not considered within the Lynch syndrome tumor spectrum. However, there are studies suggesting a contribution of microsatellite instability in sporadic uveal melanoma tumorigenesis. We report a 45-year-old woman who was referred for genetic counseling due to a family history of Lynch syndrome caused by a MLH1 mutation. She originally underwent enucleation of the right eye secondary to a uveal spindle cell melanoma diagnosed at age 25. The tumor recurred 22 years later presenting as an ovarian metastasis and concurrently a microscopic endometrial endometrioid carcinoma, grade 1/3 was diagnosed. Subsequent studies highlighted that the uveal melanoma showed high microsatellite instability and loss of MLH1 and PMS2 protein expression, with no MLH1 promoter methylation or BRAF mutation. Additionally, a GNAQ mutation was found. We conclude that our patient's uveal melanoma is most likely related to MLH1 germline mutation and thus Lynch syndrome related. To the best of our knowledge, this is the first report of uveal melanoma showing MLH1/PMS2 protein loss in the context of Lynch syndrome.

Lynch Syndrome Associated Colon Adenocarcinoma Resembling Lymphoma on Fluoro-Deoxyglucose-Positron Emission Tomography/Computed Tomography

International Nuclear Information System (INIS)

Aparici, Carina Mari; Win, Aung Zaw

2015-01-01

The patient was a 46-year-old Asian male diagnosed with lynch syndrome associated colon adenocarcinoma in the right ascending colon. A presurgical staging 18-fluoro-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) found increased metabolic activity in the cervical, axillary, mediastinal, supraclavicular, para-aortic and mesenteric lymph nodes. This pattern of metastasis was very unusual for lynch syndrome associated colon adenocarcinoma and the involvement of those lymph nodes resembles the pattern of spread of lymphoma. He underwent right hemicolectomy and he was subsequently treated with 12 cycles of folinic acid (leucovorin), fluorouracil (5-FU), irinotecan. A restaging FDG-PET/CT at the end of the chemotherapy showed interval decrease in size and metabolic activity in the affected lymph nodes. FDG-PET/CT is a useful imaging modality in following-up the treatment response in colon adenocarcinoma

Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis

DEFF Research Database (Denmark)

Hinrichsen, Inga; Brieger, Angela; Trojan, Jörg

2013-01-01

Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance. The functionality of these variants can be tested in the laboratory, but the results...

Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome

NARCIS (Netherlands)

Brouwer, Jesca G.M.; Makama, Maureen; Woudenbergh, Van Geertruida J.; Vasen, Hans F.A.; Nagengast, Fokko M.; Kleibeuker, Jan H.; Kampman, Ellen; Duijnhoven, Van Fränzel J.B.

2017-01-01

Background: Persons with Lynch syndrome (LS) have high lifetime risk of developing colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR) genes. An important process in the development of CRTs is inflammation, which has been shown to be modulated by diet.

FAUNA DAN TEMPAT PERKEMBANGBIAKAN POTENSIAL NYAMUK Anopheles spp DI KECAMATAN MAYONG, KABUPATEN JEPARA, JAWA TENGAH

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Mardiana Mardiana

2012-10-01

Full Text Available Malaria masih merupakan masalah kesehatan masyarakat di beberapa daerah pedesaan di Jawa Tengah. Usaha pemberantasan malaria telah dilakukan oleh program baik secara kimiawi maupun hayati, guna memutuskan rantai penularan. Penelitian fauna dan tempat perindukan potensial nyamuk Anopheles telah dilakukan di Desa Buaran, Kecamatan Mayong I, Kabupaten Jepara, Jawa Tengah. Penangkapan nyamuk dengan umpan orang dilakukan di dalam dan di luar rumah pada malam hari dari pukul 18.00-24.00 yang masing-masing dilakukan oleh dua orang kolektor. Penangkapan nyamuk yang istirahat di dalam dan luar rumah (vegetasi pada pagi hari dilakukan pukul 06.00-08.00, yang dilakukan satu bulan 4 kali penangkapan selama 6 bulan. Pengambilan larva dan pupa dilakukan dari pukul 06.00-08.00 pagi di tempat genangan air dan sawah serta tempat yang potensial diduga sebagai perindukan Anopheles. Hasil penangkapan selama 6 bulan, diperoleh 1248 ekor nyamuk Anopheles yang terdiri dari 6 spesies yaitu: An. aconitus 442 ekor (35,42%, An. annularis 69 ekor (5,53% , An. barbirostris 30 ekor (2,4%, An. maculatus 2 ekor (0,16%, An. tesselatus 5 ekor (0,40% dan An. vagus 700 ekor (56,09%. Populasi aconitus ditemukan dari penangkapan di luar rumah, pada bulan Juli (56,40%, Agustus (42,80% dan Oktober (39,50% sedangkan pada bulan Mei (52,9%, Juni (44% dan September (50,40% dari penangkapan di kandang sapi. Pengambilan larva dan pupa Anopheles dilakukan di tempat habitat seperti sawah yang pada bulan Aguslus terbanyak ditemukan sebesar 85 (1.70, di sungai ditemukan hanya 4 (0.08 serta di genangan air bekas telapak kaki/kobokan ditemukan sebesar 6 (0.12. Ternyata tempat perindukan yang potensial larva Anopheles pada musim kemarau, ditemukan pada sungai yang ditanami kangkung oleh masyarakat selempat. Kata kunci: Fauna, tempat perindukan, Anopheles, vector

Role for Genetic Anticipation in Lynch Syndrome

DEFF Research Database (Denmark)

Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

2009-01-01

PURPOSE: Anticipation (ie, an earlier age at onset in successive generations) is linked to repeat expansion in neurodegenerative syndromes, whereas its role in hereditary cancer is unclear. We assessed anticipation in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), in which DNA...... parent-child pairs in which age at the first cancer diagnosis was assessed. A paired t-test and a specifically developed bivariate model were used to assess a possible role of anticipation. RESULTS: Both methods revealed anticipation with children developing cancer mean 9.8 years (P ... parents using the paired t-test and 5.5 years (P anticipation with 7.2 years earlier age at onset was identified also in the oldest cohort, in which the children were observed until they were older than 80 years...

Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome.

Science.gov (United States)

Dillon, Jessica L; Gonzalez, Jorge L; DeMars, Leslie; Bloch, Katarzyna J; Tafe, Laura J

2017-12-01

Lynch syndrome (LS) is an inherited clinical syndrome characterized by a high risk of colorectal, endometrial (lifetime risk of up to 60%), ovarian, and urinary tract cancers. The diagnosis is confirmed by identification of germline mutations in the DNA mismatch repair genes MLH1, PMS2, MSH2, MSH6, or EPCAM. In 2015, our institution implemented universal screening of endometrial cancer (EC) hysterectomy specimens by mismatch repair immunohistochemistry (IHC) with reflex MLH1 promoter hypermethylation analysis for tumors with loss of MLH1/PMS2 expression. Patients with tumors negative for MLH1 methylation and those with a loss of the heterodimer pair MSH2 and MSH6, or isolated loss of either PMS2 or MSH6 were referred to the Familial Cancer Program for genetic counseling and consideration of germline testing. Between May 2015 to Dec 2016, 233 EC patients were screened by IHC for LS with a median age of 63 years. Sixty tumors (27%) had abnormal IHC staining results. Fifty-one (22%) harbored heterodimeric loss of MLH1 and PMS2, 49 of which showed MLH1 promoter methylation (1 failure, 1 negative). One showed loss of MLH1/PMS2 and MSH6, 2 showed loss of MSH2/MSH6, and 6 had isolated loss of MSH6 only. Ten patients underwent genetic counseling, and germline testing was performed in 8; LS was confirmed in 5 patients (2.1%). In addition, 3 patients with negative germline testing and presumed Lynch-like syndrome were identified and offered additional somatic testing. Universal screening for LS in EC patients has yielded positive results for identification of patients at risk for this inherited syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular comparison of topotypic specimens confirms Anopheles (Nyssorhynchus dunhami Causey (Diptera: Culicidae in the Colombian Amazon

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Freddy Ruiz

2010-11-01

Full Text Available The presence of Anopheles (Nyssorhynchus dunhami Causey in Colombia (Department of Amazonas is confirmed for the first time through direct comparison of mtDNA cytochrome c oxidase I (COI barcodes and nuclear rDNA second internal transcribed spacer (ITS2 sequences with topotypic specimens of An. dunhami from Tefé, Brazil. An. dunhami was identified through retrospective correlation of DNA sequences following misidentification as Anopheles nuneztovari s.l. using available morphological keys for Colombian mosquitoes. That An. dunhami occurs in Colombia and also possibly throughout the Amazon Basin, is of importance to vector control programs, as this non-vector species is morphologically similar to known malaria vectors including An. nuneztovari, Anopheles oswaldoi and Anopheles trinkae. Species identification of An. dunhami and differentiation from these closely related species are highly robust using either DNA ITS2 sequences or COI DNA barcode. DNA methods are advocated for future differentiation of these often sympatric taxa in South America.

First record of Anopheles stephensi in Sri Lanka: a potential challenge for prevention of malaria reintroduction.

Science.gov (United States)

Gayan Dharmasiri, A G; Perera, A Yashan; Harishchandra, Jeevanie; Herath, Hemantha; Aravindan, Kandasamy; Jayasooriya, H T R; Ranawaka, Gaya R; Hewavitharane, Mihirini

2017-08-10

The major malaria vector in Sri Lanka is reported to be Anopheles culicifacies with Anopheles subpictus, Anopheles annularis, and Anopheles varuna considered as potential vectors. The occurrence of Anopheles stephensi, which is the key vector of urban malaria in India and the Middle East, had never been reported from Sri Lanka. A series of entomological investigations were carried out by the Anti Malaria Campaign, Ministry of Health, Sri Lanka during December 2016 to April 2017 in two localities of the Mannar District in the Northern Province of the country. Adult mosquito collections were done through indoor and outdoor resting collections, animal and human biting collections and emergence traps. Potential mosquito breeding sites were investigated through larval surveys. The larvae and adults of An. stephensi were initially identified using morphological keys, and subsequently confirmed by sequencing the barcode region of the cytochrome c oxidase I (COI) gene. This is the first report of the presence of An. stephensi in the island of Mannar in the Northern Province of Sri Lanka. Anopheles stephensi (36.65%) was the most abundant anopheline species in the larval habitats in Mannar. It was found breeding together with An. culicifacies (20.7%), An. subpictus (13.5%) and An. varuna (28.13%). Anopheles stephensi was found to be abundantly breeding in built wells used for domestic purposes. Adult females of An. stephensi were observed in emergence trap collections (93.9%), human landing catches all night (79.2%), pyrethrum spray sheet collections (38.6%), outdoor collections (8.3%), donkey-baited trap collections (14.3), and cattle-baited net trap collections (0.7%). Sri Lanka was certified as malaria-free by the WHO in September 2016, however, this new finding may pose a serious challenge to the efforts of the Ministry of Health to prevent the re-introduction of malaria transmission in the country, considering the role that An. stephensi could play in urban and high

Larvicidal effects of Jatropha curcas L. against Anopheles arabiensis

African Journals Online (AJOL)

Bheema

Key words: Malaria vector control, Anopheles arabiensis, Botanical larvicides J. curcas. 1. ... The white latex serves as a disinfectant in mouth .... distilled water to serve as a negative control solution for larvicidal bioassays involving test.

[Management and Nursing care for a patient with Lynch syndrome: A case report].

Science.gov (United States)

Pacheco-Pérez, Luis Arturo; Guevara Valtier, Milton Carlos

2016-01-01

Colorectal cancer is one of the leading causes of death from cancer worldwide. Main interventions to reduce the impact are aimed to enhance prevention and early detection. Results of several studies show that tests such as the fecal occult blood test and colonoscopy are effective for early diagnosis. There are hereditary syndromes such as Lynch Syndrome that can lead to certain types of cancers, including bowel neoplasms, therefore early detection needs to be included as part of the treatment. In these cases, family genetic testing is recommended if the bowel cancer is diagnosed before 50 years old. A care plan including the NANDA (North American Nursing Diagnosis Association), NOC (Nursing Outcomes Classification) and NIC (Nursing Interventions Classification) was developed for a patient with suspected Lynch Syndrome. Nurses should be qualified to identify potential cases of cancer associated with this syndrome, and thus, reduce the likelihood that family members develop the disease, through genetic counseling and education of environmental risk factors. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Common mutations identified in the MLH1 gene in familial Lynch syndrome

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Jisha Elias

2017-12-01

In this study we identified three families with Lynch syndrome from a rural cancer center in western India (KCHRC, Goraj, Gujarat, where 70-75 CRC patients are seen annually. DNA isolated from the blood of consented family members of all three families (8-10 members/family was subjected to NGS sequencing methods on an Illumina HiSeq 4000 platform. We identified unique mutations in the MLH1 gene in all three HNPCC family members. Two of the three unrelated families shared a common mutation (154delA and 156delA. Total 8 members of a family were identified as carriers for 156delA mutation of which 5 members were unaffected while 3 were affected (age of onset: 1 member <30yrs & 2 were>40yr. The family with 154delA mutation showed 2 affected members (>40yr carrying the mutations.LYS618DEL mutation found in 8 members of the third family showed that both affected and unaffected carried the mutation. Thus the common mutations identified in the MLH1 gene in two unrelated families had a high risk for lynch syndrome especially above the age of 40.

Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations.

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Sofie V Nielsen

2017-04-01

Full Text Available Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct mechanistic insight. Here we demonstrate, for the first time, that saturation mutagenesis, biophysical modeling and co-variation analysis, performed in silico, can predict the abundance, metabolic stability, and function of proteins inside living cells. As a model system, we selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than inherent loss of function, and accordingly our in silico modeling data accurately identifies disease-causing mutations and outperforms the traditionally used genetic disease predictors. Thus, in conclusion, in silico biophysical modeling should be considered for making genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases.

Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge.

Science.gov (United States)

Lynch, Henry T; Lanspa, Stephen; Shaw, Trudy; Casey, Murray Joseph; Rendell, Marc; Stacey, Mark; Townley, Theresa; Snyder, Carrie; Hitchins, Megan; Bailey-Wilson, Joan

2018-07-01

Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical overview of the syndrome, its heterogeneity, its genomic landscape, and its implications for complex diagnosis, genetic counseling and putative implications for immunotherapy.

Factors influencing infection and transmission of Anopheles gambiae densovirus (AgDNV in mosquitoes

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Tapan K. Barik

2016-11-01

Full Text Available Anopheles gambiae densovirus (AgDNV is a potential microbial agent for paratransgenesis and gene transduction in An. gambiae, the major vector of human malaria in sub-Saharan Africa. Understanding the interaction between AgDNV and An. gambiae is critical for using AgDNV in a basic and applied manner for Anopheles gene manipulation. Here, we tested the effects of mosquito age, sex, blood feeding status, and potential for horizontal transmission using an enhanced green fluorescent protein (EGFP reporter AgDNV system. Neither mosquito age at infection nor feeding regime affected viral titers. Female mosquitoes were more permissive to viral infection than males. Despite low viral titers, infected males were able to venereally transmit virus to females during mating, where the virus was localized with the transferred sperm in the spermathecae. These findings will be useful for designing AgDNV-based strategies to manipulate Anopheles gambiae.

Factors influencing infection and transmission of Anopheles gambiae densovirus (AgDNV) in mosquitoes.

Science.gov (United States)

Barik, Tapan K; Suzuki, Yasutsugu; Rasgon, Jason L

2016-01-01

Anopheles gambiae densovirus (AgDNV) is a potential microbial agent for paratransgenesis and gene transduction in An. gambiae , the major vector of human malaria in sub-Saharan Africa. Understanding the interaction between AgDNV and An. gambiae is critical for using AgDNV in a basic and applied manner for Anopheles gene manipulation. Here, we tested the effects of mosquito age, sex, blood feeding status, and potential for horizontal transmission using an enhanced green fluorescent protein (EGFP) reporter AgDNV system. Neither mosquito age at infection nor feeding regime affected viral titers. Female mosquitoes were more permissive to viral infection than males. Despite low viral titers, infected males were able to venereally transmit virus to females during mating, where the virus was localized with the transferred sperm in the spermathecae. These findings will be useful for designing AgDNV-based strategies to manipulate Anopheles gambiae .

The physicochemical and environmental factors affecting the distribution of Anopheles merus along the Kenyan coast.

Science.gov (United States)

Kipyab, Pamela C; Khaemba, Battan M; Mwangangi, Joseph M; Mbogo, Charles M

2015-04-11

Members of the Anopheles gambiae complex are the main transmitters of malaria. Anopheles merus is a member of the complex found along the Kenyan coast because it breeds in saline waters. An entomological study was conducted in Garithe Malindi District, to investigate the physicochemical and environmental factors affecting the distribution of An. merus. Field and laboratory studies were used to investigate the breeding habitats of the subspecies. Mosquito larvae were sampled using standard dipping technique from small pockets of pools, ponds, hoof prints, road drain, wells and mangrove swamps found in Garithe. All 3(rd) and 4(th) instars of Anopheles larvae sampled were identified microscopically into species. A representative of Anopheles gambiae complex was then identified to specific sibling species using r-DNA PCR technique. The habitats were characterized based on temperature, conductivity, salinity, dissolved oxygen, total dissolved solids, pH, size, distance to nearest house, canopy coverage, surface debris, presence of algae, emergent plants, turbidity and habitat types. A total of 159 morphologically identified late stage instar Anopheles gambiae s.l larvae were selected for r-DNA analysis by PCR. Out of these, 60.4% (n = 96) were Anopheles merus, 8.8% (n = 14) were Anopheles arabiensis, 18.2% (n = 29) were Anopheles gambiae s.s and 12.6% (n = 20) were unknown. Using paired t-test (t (121) = -3.331, P = 0.001) a significantly high proportion of An. merus was observed in all habitats compared to An. arabiensis, and An. gambiae s. s. In habitat characterization, Pearson's correlation analysis test showed different parameters being associated with the occurrence of An. merus larvae in the different habitats sampled. Six out of the 55 correlation coefficients (10.9%) were statistically significant, suggesting non-random association between some pairs of variables. Those that had a significantly high positive correlation with An. merus

Una nueva técnica para el estudio microscópico de los huevos de Anopheles Una nueva técnica para el estudio microscópico de los huevos de Anopheles

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Osorno-Mesa Ernesto

1947-12-01

Full Text Available A new method is described for dissection and mounting of the exochorion of Anopheles eggs, for microscopic study, which has advantages over previous methods. The possible taxocomic importance of the morphology of the micropyle, clearly seen by this method, is noted. Se describe una técnica original para el estudio microscópico de los huevos de Anopheles, fundamentada en la disección del exocorion, indicando las grandes ventajas que tiene. Se anota la importancia taxonómica que pueda tener la morfología del micrópilo. / Abstract. A new method is described for dissection and mounting of the exochorion of Anopheles eggs, for microscopic study, which has advantages over previous methods. The possible taxocomic importance of the morphology of the micropyle, clearly seen by this method, is noted.

Phylogenetic study of six species of Anopheles mosquitoes in Peninsular Malaysia based on inter-transcribed spacer region 2 (ITS2) of ribosomal DNA.

Science.gov (United States)

Sum, Jia-Siang; Lee, Wenn-Chyau; Amir, Amirah; Braima, Kamil A; Jeffery, John; Abdul-Aziz, Noraishah M; Fong, Mun-Yik; Lau, Yee-Ling

2014-07-03

Molecular techniques are invaluable for investigation on the biodiversity of Anopheles mosquitoes. This study aimed at investigating the spatial-genetic variations among Anopheles mosquitoes from different areas of Peninsular Malaysia, as well as deciphering evolutionary relationships of the local Anopheles mosquitoes with the mosquitoes from neighbouring countries using the anopheline ITS2 rDNA gene. Mosquitoes were collected, identified, dissected to check infection status, and DNA extraction was performed for PCR with primers targeting the ITS2 rDNA region. Sequencing was done and phylogenetic tree was constructed to study the evolutionary relationship among Anopheles mosquitoes within Peninsular Malaysia, as well as across the Asian region. A total of 133 Anopheles mosquitoes consisting of six different species were collected from eight different locations across Peninsular Malaysia. Of these, 65 ITS2 rDNA sequences were obtained. The ITS2 rDNA amplicons of the studied species were of different sizes. One collected species, Anopheles sinensis, shows two distinct pools of population in Peninsular Malaysia, suggesting evolvement of geographic race or allopatric speciation. Anopheles mosquitoes from Peninsular Malaysia show close evolutionary relationship with the Asian anophelines. Nevertheless, genetic differences due to geographical segregation can be seen. Meanwhile, some Anopheles mosquitoes in Peninsular Malaysia show vicariance, exemplified by the emergence of distinct cluster of An. sinensis population.

Larvicidal activity of six Nigerian plant species against Anopheles ...

African Journals Online (AJOL)

This study evaluated the larvicidal activity of extracts from six Nigerian plant species (Zanthoxylum zanthoxyloides, Piper guineense, Nicotianat abacum, Erythrophleum suaveoleus, Jatropha curcas and Petiveria alliacea) against laboratory-bred Anopheles gambiae and Aedes aegypti larvae. Zanthoxylum zanthoxyloides ...

Interval colon cancer in a Lynch syndrome patient under annual colonoscopic surveillance: a case for advanced imaging techniques?

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Oxentenko Amy S

2012-05-01

Full Text Available Abstract Background Lynch syndrome confers increased risk for various malignancies, including colorectal cancer. Colonoscopic surveillance programs have led to reduced incidence of colorectal cancer and reduced mortality from colorectal cancer. Colonoscopy every 1–2 years beginning at age 20–25, or 10 years earlier than the first diagnosis of colorectal cancer in a family, with annual colonoscopy after age 40, is the recommended management for mutation carriers. Screening programs have reduced colon cancer mortality, but interval cancers may occur. Case presentation We describe a 48-year-old woman with Lynch syndrome who was found to have an adenoma with invasive colorectal cancer within one year after a normal colonoscopy. Conclusion Our patient illustrates two current concepts about Lynch syndrome: 1 adenomas are the cancer precursor and 2 such adenomas may be “aggressive,” in the sense that the adenoma progresses more readily and more rapidly to carcinoma in this setting compared to usual colorectal adenomas. Our patient’s resected tumor invaded only into submucosa and all lymph nodes were negative; in that sense, she represents a success for annual colonoscopic surveillance. Still, this case does raise the question of whether advanced imaging techniques are advisable for surveillance colonoscopy in these high-risk patients.

Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

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Francesca Duraturo

2013-01-01

Full Text Available Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR genes, mainly MLH1 and MSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2 genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6 in one of the patients analysed (1.6% frequency. This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement within MSH2 gene and showed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.

The invasive shrub Prosopis juliflora enhances the malaria parasite transmission capacity of Anopheles mosquitoes: a habitat manipulation experiment.

Science.gov (United States)

Muller, Gunter C; Junnila, Amy; Traore, Mohamad M; Traore, Sekou F; Doumbia, Seydou; Sissoko, Fatoumata; Dembele, Seydou M; Schlein, Yosef; Arheart, Kristopher L; Revay, Edita E; Kravchenko, Vasiliy D; Witt, Arne; Beier, John C

2017-07-05

A neglected aspect of alien invasive plant species is their influence on mosquito vector ecology and malaria transmission. Invasive plants that are highly attractive to Anopheles mosquitoes provide them with sugar that is critical to their survival. The effect on Anopheles mosquito populations was examined through a habitat manipulation experiment that removed the flowering branches of highly attractive Prosopis juliflora from selected villages in Mali, West Africa. Nine villages in the Bandiagara district of Mali were selected, six with flowering Prosopis juliflora, and three without. CDC-UV light traps were used to monitor their Anopheles spp. vector populations, and recorded their species composition, population size, age structure, and sugar feeding status. After 8 days, all of the flowering branches were removed from three villages and trap catches were analysed again. Villages where flowering branches of the invasive shrub Prosopis juliflora were removed experienced a threefold drop in the older more dangerous Anopheles females. Population density dropped by 69.4% and the species composition shifted from being a mix of three species of the Anopheles gambiae complex to one dominated by Anopheles coluzzii. The proportion of sugar fed females dropped from 73 to 15% and males from 77 to 10%. This study demonstrates how an invasive plant shrub promotes the malaria parasite transmission capacity of African malaria vector mosquitoes. Proper management of invasive plants could potentially reduce mosquito populations and malaria transmission.

Ecology of Anopheline (Diptera, Culicidae, malaria vectors around the Serra da Mesa Reservoir, State of Goiás, Brazil: 1 - Frequency and climatic factors

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Anthony Érico Guimarães

Full Text Available The ecology of anopheline species (Diptera, Culicidae was studied in the vicinity of the Serra da Mesa Reservoir, State of Goiás, Brazil. Climatic factors and frequency of anopheline populations were analyzed. Bimonthly human-bait and Shannon trap captures were conducted for 36 consecutive months (January 1997 through December 1999. A total of 5,205 adult anophelines belonging to five species were collected. Anopheles darlingi was the most frequently collected anopheline (61.4%, followed by An. albitarsis s.l. (35.4%, An. triannulatus. (2.5%, An. oswaldoi (0.4%, and An. evansae (0.2%. The water level and vegetation along the banks of the reservoir were crucial to the frequency of the various anopheline species. Climatic factors had a secondary influence. The reservoir's water-level stability, increased frequency of An. darlingi, and the arrival of gold prospectors were responsible for the increase in malaria cases.

Viruses in the Anopheles A, Anopheles B, and Tete serogroups in the Orthobunyavirus genus (family Bunyaviridae) do not encode an NSs protein.

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Mohamed, Maizan; McLees, Angela; Elliott, Richard M

2009-08-01

Viruses in the genus Orthobunyavirus, family Bunyaviridae, have a genome comprising three segments (called L, M, and S) of negative-sense RNA. Serological studies have classified the >170 named virus isolates into 18 serogroups, with a few additional as yet ungrouped viruses. Until now, molecular studies and full-length S-segment nucleotide sequences were available for representatives of eight serogroups; in all cases, the S segment encodes two proteins, N (nucleocapsid) and NSs (nonstructural), in overlapping open reading frames (ORFs) that are translated from the same mRNA. The NSs proteins of Bunyamwera virus (BUNV) and California serogroup viruses have been shown to play a role in inhibiting host cell mRNA and protein synthesis, thereby preventing induction of interferon (IFN). We have determined full-length sequences of the S segments of representative viruses in the Anopheles A, Anopheles B, and Tete serogroups, and we report here that these viruses do not show evidence of having an NSs ORF. In addition, these viruses have rather longer N proteins than those in the other serogroups. Most of the naturally occurring viruses that lack the NSs protein behaved like a recombinant BUNV with the NSs gene deleted in that they failed to prevent induction of IFN-beta mRNA. However, Tacaiuma virus (TCMV) in the Anopheles A serogroup inhibited IFN induction in a manner similar to that of wild-type BUNV, suggesting that TCMV has evolved an alternative mechanism, not involving a typical NSs protein, to antagonize the host innate immune response.

Susceptibility Status of The Malaria Vector Anopheles Arabiensis To ...

African Journals Online (AJOL)

Background: Increasing insecticide resistancein the major anopheline vectors remain the main obstacle for malaria control programmes in African countries including Sudan. Objectives: To assess the susceptibility status of Anopheles arabiensis the malaria vector to different classes of insecticides in Khartoum State.

Phylogenetic study of six species of Anopheles mosquitoes in Peninsular Malaysia based on inter-transcribed spacer region 2 (ITS2) of ribosomal DNA

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2014-01-01

Background Molecular techniques are invaluable for investigation on the biodiversity of Anopheles mosquitoes. This study aimed at investigating the spatial-genetic variations among Anopheles mosquitoes from different areas of Peninsular Malaysia, as well as deciphering evolutionary relationships of the local Anopheles mosquitoes with the mosquitoes from neighbouring countries using the anopheline ITS2 rDNA gene. Methods Mosquitoes were collected, identified, dissected to check infection status, and DNA extraction was performed for PCR with primers targeting the ITS2 rDNA region. Sequencing was done and phylogenetic tree was constructed to study the evolutionary relationship among Anopheles mosquitoes within Peninsular Malaysia, as well as across the Asian region. Results A total of 133 Anopheles mosquitoes consisting of six different species were collected from eight different locations across Peninsular Malaysia. Of these, 65 ITS2 rDNA sequences were obtained. The ITS2 rDNA amplicons of the studied species were of different sizes. One collected species, Anopheles sinensis, shows two distinct pools of population in Peninsular Malaysia, suggesting evolvement of geographic race or allopatric speciation. Conclusion Anopheles mosquitoes from Peninsular Malaysia show close evolutionary relationship with the Asian anophelines. Nevertheless, genetic differences due to geographical segregation can be seen. Meanwhile, some Anopheles mosquitoes in Peninsular Malaysia show vicariance, exemplified by the emergence of distinct cluster of An. sinensis population. PMID:24993022

Field performance of timber bridges. 8, Lynches Woods Park stress-laminated deck bridge

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J. P. Wacker; M. A. Ritter; D. Conger

The Lynches Woods Park bridge was constructed during the summer of 1990 in Newberry, South Carolina. It is a single-span, single-lane, stress-laminated deck superstructure that measures approximately 30 ft long, 16 ft wide, and 14 in. deep. The bridge is unique in that is one of the first known stress-laminated deck bridges to be constructed of Southern Pine lumber...

Molecular identification of a myosuppressin receptor from the malaria mosquito Anopheles gambiae

DEFF Research Database (Denmark)

Schöller, Susanne; Belmont, Martin; Cazzamali, Giuseppe

2005-01-01

The insect myosuppressins (X1DVX2HX3FLRFamide) are neuropeptides that generally block insect muscle activities. We have used the genomic sequence information from the malaria mosquito Anopheles gambiae Genome Project to clone a G protein-coupled receptor that was closely related to the two...... previously cloned and characterized myosuppressin receptors from Drosophila [Proc. Natl. Acad. Sci. USA 100 (2003) 9808]. The mosquito receptor cDNA was expressed in Chinese hamster ovary cells and was found to be activated by low concentrations of Anopheles myosuppressin (TDVDHVFLRFamide; EC50, 1.6 x 10...... identification of a mosquito neuropeptide receptor....

Determinants of adherence to recommendations for cancer prevention among Lynch Syndrome mutation carriers : A qualitative exploration

NARCIS (Netherlands)

Visser, Annemiek; Vrieling, Alina; Murugesu, Laxsini; Hoogerbrugge, Nicoline; Kampman, Ellen; Hoedjes, Meeke

2017-01-01

Background: Lynch Syndrome (LS) mutation carriers are at high risk for various cancer types, particularly colorectal cancer. Adherence to lifestyle and body weight recommendations for cancer prevention may lower this risk. To promote adherence to these recommendations, knowledge on determinants of

Determinants of adherence to recommendations for cancer prevention among Lynch Syndrome mutation carriers: a qualitative exploration.

NARCIS (Netherlands)

Visser, A.; Vrieling, A.; Murugesu, L.; Hoogerbrugge, N.; Kampman, E.; Hoedjes, M.

2017-01-01

Background: Lynch Syndrome (LS) mutation carriers are at high risk for various cancer types, particularly colorectal cancer. Adherence to lifestyle and body weight recommendations for cancer prevention may lower this risk. To promote adherence to these recommendations, knowledge on determinants of

Prospective multicenter randomized intermediate biomarker study of oral contraceptive versus depo-provera for prevention of endometrial cancer in women with Lynch syndrome.

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Lu, Karen H; Loose, David S; Yates, Melinda S; Nogueras-Gonzalez, Graciela M; Munsell, Mark F; Chen, Lee-May; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M; Broaddus, Russell R

2013-08-01

Women with Lynch syndrome have a 40% to 60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have shown that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown whether they are effective in women with Lynch syndrome. Asymptomatic women ages 25 to 50 with Lynch syndrome were randomized to receive the progestin compounds Depo-Provera (depo-MPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were conducted before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depo-MPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results show that women with Lynch syndrome do show an endometrial response to short-term exogenous progestins, suggesting that OCP and depo-MPA may be reasonable chemopreventive agents in this high-risk patient population.

Composition of Anopheles Species Collected from Selected Malarious Areas of Afghanistan and Iran

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Helen Hoosh-Deghati

2017-10-01

Full Text Available Background: Malarious areas in Iran are close to Afghanistan and Pakistan that urge the researchers to extend their knowledge on malaria epidemiology to the neighboring countries as well. Vectorial capacity differs at species or even at population level, the first essential step is accurate identification of vectors. This study aimed to identify Anopheles species composition in selected malarious areas of Afghanistan and Iran, providing further applied data for other research in two countries.Methods: Adults Anopheles spp. were collected from four provinces in Afghanistan (Badakhshan, Herat, Kunduz, Nangarhar by pyrethrum spray catch, hand collection methods through WHO/EMRO coordination and from Chaba­har County in Iran by pyrethrum spray catch method. Identification was performed using reliable identification key.Results: Totally, 800 female Anopheles mosquitos, 400 from each country were identified at species level. Anophe­les composition in Afghanistan was An. superpictus, An. stephensi and An. hyrcanus. Most prevalent species in Ba­dakhshan and Kunduz were An. superpictus, whereas An. stephensi and An. hyrcanus were respectively found in Nangarhar and Heart. Anopheles species in Chabahar County of Iran were An. stephensi, An. fluviatilis, An. culicifa­cies and An. sergentii. The most prevalent species was An. stephensi.Conclusion: Current study provides a basis for future research such as detection of Plasmodium infection in col­lected samples which is on process by the authors, also for effective implementation of evidence-based malaria vec­tor intervention strategies.

Sperm quantity and size variation in un-irradiated and irradiated males of the malaria mosquito Anopheles arabiensis Patton

NARCIS (Netherlands)

Helinski, M.; Knols, B.G.J.

2009-01-01

Anopheles mosquitoes are important candidates for genetic control strategies. However, little is known about sperm quality and quantity as determinants of male reproductive success. In this study, sperm quantity and length variation were assessed in testes of un-irradiated and irradiated Anopheles

An {sup 57}Fe Mössbauer study of the ordinary chondrite meteorite Lynch 001

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Elewa, Nancy N., E-mail: nancy.elewa@student.unsw.edu.au; Cadogan, J. M. [The University of New South Wales at the Australian Defence Force Academy, School of Physical, Environmental and Mathematical Sciences (Australia)

2017-11-15

The Lynch 001 meteorite was found in the Nullarbor Plain region of Western Australia in 1977. This meteorite is classified as an ordinary chondrite of the petrologic group L5/6 that has undergone ‘minor to moderate’ terrestrial weathering. Here, we characterize the Fe-bearing phases in this chondrite using {sup 57}Fe Mössbauer spectroscopy carried out over the temperature range 13 K to room temperature (295 K). The paramagnetic doublets of olivine, pyroxene and a superparamagnetic ferric phase dominate the room temperature Mössbauer spectrum. On the basis of the room temperature quadrupole splitting of the olivine component, we estimate its composition to be Fa {sub 30(5)}. Besides the paramagnetic ferric component, accounting for ∼15 % of the spectral area at room temperature, magnetically ordered ferric phases were also detected. The total relative proportion of the Fe {sup 3+} components allows us to estimate the terrestrial age of Lynch 001 to be 6,500 ± 1,500 yr, consistent with the value of 6,700 ± 1,300 yr determined by {sup 14}C dating.

Changes in screening behaviors and attitudes toward screening from pre-test genetic counseling to post-disclosure in Lynch syndrome families

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Burton-Chase, Allison M.; Hovick, Shelly R.; Peterson, Susan K.; Marani, Salma K.; Vernon, Sally W.; Amos, Christopher I.; Frazier, Marsha L.; Lynch, Patrick M.; Gritz, Ellen R.

2013-01-01

Purpose This study examined colonoscopy adherence and attitudes towards colorectal cancer (CRC) screening in individuals who underwent Lynch syndrome genetic counseling and testing. Methods We evaluated changes in colonoscopy adherence and CRC screening attitudes in 78 cancer-unaffected relatives of Lynch syndrome mutation carriers before pre-test genetic counseling (baseline) and at 6 and 12 months post-disclosure of test results (52 mutation-negative, 26 mutation-positive). Results While both groups were similar at baseline, at 12 months post-disclosure, a greater number of mutation-positive individuals had had a colonoscopy compared with mutation-negative individuals. From baseline to 12 months post-disclosure, the mutation-positive group demonstrated an increase in mean scores on measures of colonoscopy commitment, self-efficacy, and perceived benefits of CRC screening, and a decrease in mean scores for perceived barriers to CRC screening. Mean scores on colonoscopy commitment decreased from baseline to 6 months in the mutation-negative group. Conclusion Adherence to risk-appropriate guidelines for CRC surveillance improved after genetic counseling and testing for Lynch syndrome. Mutation-positive individuals reported increasingly positive attitudes toward CRC screening after receiving genetic test results, potentially reinforcing longer term colonoscopy adherence. PMID:23414081

Comparison of extended colectomy and limited resection in patients with Lynch syndrome.

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Natarajan, Nagendra; Watson, Patrice; Silva-Lopez, Edibaldo; Lynch, Henry T

2010-01-01

The purpose of the study was to determine the advantages and disadvantages of prophylactic/extended colectomy (subtotal colectomy) in patients with Lynch syndrome who manifest colorectal cancer. A retrospective cohort using Creighton University's hereditary cancer database was used to identify cases and controls. Cases are patients who underwent subtotal colectomy, either with no colorectal cancer diagnosis (prophylactic) or at diagnosis of first colorectal cancer; controls for these 2 types of cases were, respectively, patients who underwent no colon surgery or those having limited resection at time of diagnosis of first colorectal cancer. The Kaplan-Meier and proportional hazard regression models from the Statistical Analysis Software program was used to calculate the difference in survival, time to subsequent colorectal cancer, and subsequent abdominal surgery between cases and controls. The event-free survival of our study did not reach 50%, so we used the event-free survival at 5 years as our parameter to compare the 2 groups. The event-free survival for subsequent colorectal cancer, subsequent abdominal surgery, and death was 94%, 84%, and 93%, respectively, for cases and 74%, 63%, and 88%, respectively, for controls. Times to subsequent colorectal cancer and subsequent abdominal surgery were significantly shorter in the control group (P Lynch syndrome.

Germline Hypermethylation of MLH1 and EPCAM Deletions Are a Frequent Cause of Lynch Syndrome

NARCIS (Netherlands)

Niessen, Renee C.; Hofstra, Robert M. W.; Westers, Helga; Ligtenberg, Marjolijn J. L.; Kooi, Krista; Jager, Paul O. J.; de Groote, Marloes L.; Dijkhuizen, Trijnie; Olderode-Berends, Maran J. W.; Hollema, Harry; Kleibeuker, Jan H.; Sijmons, Rolf H.

It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters. Furthermore, it has been demonstrated very recently that germline deletions of the 3' region of EPCAM cause transcriptional read-through which results in silencing of MSH2 by hypermethylation.

Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome.

NARCIS (Netherlands)

Niessen, R.C.; Hofstra, R.M.; Westers, H.; Ligtenberg, M.J.L.; Kooi, K.; Jager, P.O.; Groote, M.L. de; Dijkhuizen, T.; Olderode-Berends, M.J.; Hollema, H.; Kleibeuker, J.H.; Sijmons, R.H.

2009-01-01

It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters. Furthermore, it has been demonstrated very recently that germline deletions of the 3' region of EPCAM cause transcriptional read-through which results in silencing of MSH2 by hypermethylation.

Bayesian Modeling for Genetic Anticipation in Presence of Mutational Heterogeneity: A Case Study in Lynch Syndrome

DEFF Research Database (Denmark)

Boonstra, Philip S; Mukherjee, Bhramar; Taylor, Jeremy M G

2011-01-01

to cause hereditary nonpolyposis colorectal cancer, also called Lynch syndrome (LS). We find evidence for a decrease in AOO between generations in this article. Our model predicts family-level anticipation effects that are potentially useful in genetic counseling clinics for high-risk families....

Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer.

Science.gov (United States)

Yamada, Rin; Yamaguchi, Tatsuro; Iijima, Takeru; Wakaume, Rika; Takao, Misato; Koizumi, Koichi; Hishima, Tsunekazu; Horiguchi, Shin-Ichiro

2018-06-01

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55-37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50-45.0, P = 0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

Filling the gap 115 years after Ronald Ross: the distribution of the Anopheles coluzzii and Anopheles gambiae s.s from Freetown and Monrovia, West Africa.

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Dziedzom K de Souza

Full Text Available It was in Freetown, Sierra Leone, that the malaria mosquito Anopheles coastalis, now known as Anopheles gambiae, was first discovered as the vector of malaria, in 1899. That discovery led to a pioneering vector research in Sierra Leone and neighbouring Liberia, where mosquito species were extensively characterized. Unfortunately, the decade long civil conflicts of the 1990s, in both countries, resulted in a stagnation of the once vibrant research on disease vectors. This paper attempts to fill in some of the gaps on what is now known of the distribution of the sibling species of the An. gambiae complex, and especially the An. coluzzii and An. gambiae s.s, formerly known as the An. gambiae molecular M and S forms respectively, in the cities of Freetown and Monrovia.

Quantitative real-time PCR analysis of Anopheles dirus TEP1 and NOS during Plasmodium berghei infection, using three reference genes

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Jonathan W.K. Liew

2017-07-01

Full Text Available Quantitative reverse transcription PCR (qRT-PCR has been an integral part of characterizing the immunity of Anopheles mosquitoes towards Plasmodium invasion. Two anti-Plasmodium factors of Anopheles, thioester-containing protein 1 (TEP1 and nitric oxide synthase (NOS, play a role in the refractoriness of Anopheles towards Plasmodium infection and are generally expressed during infection. However, these are less studied in Anopheles dirus, a dominant malaria vector in Southeast Asia. Furthermore, most studies used a single reference gene for normalization during gene expression analysis without proper validation. This may lead to erroneous quantification of expression levels. Therefore, the present study characterized and investigated the expression profiles of TEP1 and NOS of Anopheles dirus during P. berghei infection. Prior to that, the elongation factor 1-alpha (EF1, actin 1 (Act and ribosomal protein S7 (S7 genes were validated for their suitability as a set of reference genes. TEP1 and NOS expressions in An. dirus were found to be significantly induced after P. berghei infection.

Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors

DEFF Research Database (Denmark)

Ketabi, Zohreh; Bartuma, Katarina; Bernstein, Inge

2011-01-01

. The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed. CONCLUSION: The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch...

Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome.

Science.gov (United States)

Burn, John; Bishop, D Timothy; Mecklin, Jukka-Pekka; Macrae, Finlay; Möslein, Gabriela; Olschwang, Sylviane; Bisgaard, Marie-Luise; Ramesar, Raj; Eccles, Diana; Maher, Eamonn R; Bertario, Lucio; Jarvinen, Heikki J; Lindblom, Annika; Evans, D Gareth; Lubinski, Jan; Morrison, Patrick J; Ho, Judy W C; Vasen, Hans F A; Side, Lucy; Thomas, Huw J W; Scott, Rodney J; Dunlop, Malcolm; Barker, Gail; Elliott, Faye; Jass, Jeremy R; Fodde, Ricardo; Lynch, Henry T; Mathers, John C

2008-12-11

Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon. In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome. Among 1071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups. Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed. The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.) 2008 Massachusetts Medical Society

Evaluation of Insecticides Susceptibility and Malaria Vector Potential of Anopheles annularis s.l. and Anopheles vagus in Assam, India.

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Sunil Dhiman

Full Text Available During the recent past, development of DDT resistance and reduction to pyrethroid susceptibility among the malaria vectors has posed a serious challenge in many Southeast Asian countries including India. Current study presents the insecticide susceptibility and knock-down data of field collected Anopheles annularis sensu lato and An. vagus mosquito species from endemic areas of Assam in northeast India. Anopheles annularis s.l. and An. vagus adult females were collected from four randomly selected sentinel sites in Orang primary health centre (OPHC and Balipara primary health centre (BPHC areas, and used for testing susceptibility to DDT, malathion, deltamethrin and lambda-cyhalothrin. After insecticide susceptibility tests, mosquitoes were subjected to VectorTest™ assay kits to detect the presence of malaria sporozoite in the mosquitoes. An. annularis s.l. was completely susceptible to deltamethrin, lambda-cyhalothrin and malathion in both the study areas. An. vagus was highly susceptible to deltamethrin in both the areas, but exhibited reduced susceptibility to lambda-cyhalothrin in BPHC. Both the species were resistant to DDT and showed very high KDT50 and KDT99 values for DDT. Probit model used to calculate the KDT50 and KDT99 values did not display normal distribution of percent knock-down with time for malathion in both the mosquito species in OPHC (p<0.05 and An. vagus in BPHC (χ2 = 25.3; p = 0.0, and also for deltamethrin to An. vagus in BPHC area (χ2 = 15.4; p = 0.004. Minimum infection rate (MIR of Plasmodium sporozoite for An. vagus was 0.56 in OPHC and 0.13 in BPHC, while for An. annularis MIR was found to be 0.22 in OPHC. Resistance management strategies should be identified to delay the expansion of resistance. Testing of field caught Anopheles vectors from different endemic areas for the presence of malaria sporozoite may be useful to ensure their role in malaria transmission.

Species\\' identification of Anopheles and Culex mosquitoes and its ...

African Journals Online (AJOL)

Indoor and outdoor bites' collections of gravid Anopheles and Culex mosquitoes were made with plastic aspirator from residential areas within Jimeta-Yola metropolis for three years (between March and May; August and October 2003 to 2005). They were identified using standard morphological keys and polymerase chain ...

Prospective, Multi-center Randomized Intermediate Biomarker Study of Oral Contraceptive vs. Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome

Science.gov (United States)

Lu, Karen H.; Loose, David S.; Yates, Melinda S.; Nogueras-Gonzalez, Graciela M.; Munsell, Mark F.; Chen, Lee-may; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S.; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M.; Broaddus, Russell R.

2013-01-01

Women with Lynch syndrome have a 40–60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have demonstrated that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown if they are effective in women with Lynch syndrome. Asymptomatic women age 25–50 with Lynch syndrome were randomized to receive the progestin compounds depo-Provera (depoMPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were performed before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depoMPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results demonstrate that women with Lynch syndrome do show an endometrial response to short term exogenous progestins, suggesting that OCP and depoMPA may be reasonable chemopreventive agents in this high-risk patient population. PMID:23639481

Enkapsulasi B. bassiana menggunakan maizena dan daya infeksinya terhadap larva Aedes aegypti, Anopheles sp., Culex sp.

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Mutiara Widawati

2015-12-01

Full Text Available Abstract. Encapsulation formulae of mycoinsecticide have to be able to maintain fungus viability and pathogenicity. This mycoinsecticide was developed as an alternative way to control mosquito borne disease. The aim of this study was to encapsulate Beauveria bassiana as viable storage and have the capability to kill larvae of Aedes aegypti, Anopheles sp. and Culex sp. Mosquito larvae obtained from laboratory reared at health research laboratory; Loka Litbang P2B2 Ciamis. The treatments made in this study were the formu-lation of cornstarch and controls for comparison. This study showed potential formulation of cornstarch encapsulation as a biolarvacidal. Cornstarch formulations proven to be succeed in maintaining fungus viability, however, the pathogenicity of the microcapsule still not effective to kill Aedes, Culex and Anopheles larvae. Keywords: encapsulation, Beauveria bassiana, Ae.aegypti, Anopheles sp., Culex sp. Abstrak. Pembuatan formula bioinsektisida yang optimal sebagai salah satu alternatif untuk pengen-dalian nyamuk vektor perlu di kembangkan. Sediaan mikoinsektisida yang dibuat harus dapat memper-tahankan viabilitas jamur B. bassiana sehingga masih efektif pada saat penggunaannya. Salah satu cara yang digunakan untuk menjaga kestabilan sediaan mikoinsektisida yang berdampak langsung pada via-bilitas jamur adalah dengan menerapkan metode enkapsulasi. Penelitian ini bertujuan untuk meng-hasilkan sediaan mikokapsul dari Beauvaria bassiana melalui proses enkapsulasi menggunakan maizena yang memiliki kapabilitas tinggi sebagai penyimpan B. bassiana dan efektif dalam membunuh larva dan telur Aedes aegypti, Anopheles sp. dan Culex sp. Semua larva uji berasal dari insektarium laboratorium penelitian kesehatan Loka litbang P2B2 Ciamis. Pembuatan enkapsulasi dimulai dengan kultur dan pema-nenan B. bassiana, uji viabilitas, proses enkapsulasi serta uji larvasida di laboratorium. Uji dilakukan dengan satu perlakuan dan satu kontrol untuk

Novel peptide marker corresponding to salivary protein gSG6 potentially identifies exposure to Anopheles bites.

Directory of Open Access Journals (Sweden)

Anne Poinsignon

2008-06-01

Full Text Available In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites.Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i their potential antigenic properties and ii the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1.This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing techniques, for mapping the risk of malaria. It could

Lynch, Urry and city marketing: Taking advantage of the city as a built and graphic image

NARCIS (Netherlands)

Hospers, G-J.

2009-01-01

City marketing is usually addressed from the perspective of marketing theory. This article follows an alternative approach by exploring city marketing from the viewpoint of urban planning and the sociology of tourism. In his classic ‘The Image of the City’ (1960), planner Kevin Lynch found that

Uncertainties in the Management of a Lynch Syndrome Patient: A Case Report

OpenAIRE

Campos, Sara; Amaro, Pedro; Cunha, Inês; Fraga, João; Cipriano, Maria Augusta; Tomé, Luís

2017-01-01

Introduction: Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is characterized by mutations in mismatch repair (MMR) genes leading to an increased cancer risk, namely colorectal cancer. Case: In the context of surveillance colonoscopy, a 40-mm flat lesion (0-IIa+b, Paris classification) was identified and submitted to piecemeal mucosal endoscopic resection in a 64-year-old LS patient with an MLH1 germline mutation (262delATC) and two previous segmental resections d...

A Systematic Review on the Existing Screening Pathways for Lynch Syndrome Identification

OpenAIRE

Tognetto, Alessia; Michelazzo, Maria Benedetta; Calabró, Giovanna Elisa; Unim, Brigid; Di Marco, Marco; Ricciardi, Walter; Pastorino, Roberta; Boccia, Stefania

2017-01-01

Background Lynch syndrome (LS) is the most common hereditary colon cancer syndrome, accounting for 3–5% of colorectal cancer (CRC) cases, and it is associated with the development of other cancers. Early detection of individuals with LS is relevant, since they can take advantage of life-saving intensive care surveillance. The debate regarding the best screening policy, however, is far from being concluded. This prompted us to conduct a systematic review of the existing screening pathways for ...

Biological activities of four essential oils against Anopheles gambiae ...

African Journals Online (AJOL)

The control of malaria is still a challenge partly due to mosquito's resistance to current available insecticides. The aim of this work was to evaluate the ovicidal, larvicidal and repellent activities of Lantana camara, Hyptis suaveolens, Hyptis spicigera and Ocimum canum essential oils against Anopheles gambiae s.l. ...

Models for Immune Response and Immune Evasion in MSI Cancer and Lynch Syndrome

OpenAIRE

Özcan, Mine

2017-01-01

Microsatellite-unstable (MSI) cancers occurring in the context of the hereditary Lynch syndrome or as sporadic cancers elicit pronounced tumor-specific immune responses. The pronounced immune response was shown to be closely associated with frameshift peptides (FSP) that are generated as a result of deficiency in DNA mismatch repair system leading to insertion/deletion mutations in coding microsatellites (cMS). FSP neoantigens are long antigenic amino acid stretches that bear m...

Pupal habitat productivity of Anopheles gambiae complex mosquitoes in a rural village in western Kenya.

Science.gov (United States)

Mutuku, Francis M; Bayoh, M Nabie; Gimnig, John E; Vulule, John M; Kamau, Luna; Walker, Edward D; Kabiru, Ephantus; Hawley, William A

2006-01-01

The productivity of larval habitats of the malaria vector Anopheles gambiae for pupae (the stage preceding adult metamorphosis) is poorly known, yet adult emergence from habitats is the primary determinant of vector density. To assess it, we used absolute sampling methods in four studies involving daily sampling for 25 days in 6 habitat types in a village in western Kenya. Anopheles gambiae s.s. comprised 82.5% of emergent adults and Anopheles arabiensis the remainder. Pupal production occurred from a subset of habitats, primarily soil burrow pits, and was discontinuous in time, even when larvae occupied all habitats continuously. Habitat stability was positively associated with pupal productivity. In a dry season, pupal productivity was distributed between burrow pits and pools in streambeds. Overall, these data support the notion that source reduction measures against recognizably productive habitats would be a useful component of an integrated management program for An. gambiae in villages.

Cannibalism and predation among larvae of the Anopheles gambiae complex

NARCIS (Netherlands)

Koenraadt, C.J.M.; Takken, W.

2003-01-01

Among the aquatic developmental stages of the Anopheles gambiae complex (Diptera: Culicidae), both inter- and intra-specific interactions influence the resulting densities of adult mosquito populations. For three members of the complex, An. arabiensis Patton, An. quadriannulatus (Theobald) and An.

Malaria case in Madagascar, probable implication of a new vector, Anopheles coustani.

Science.gov (United States)

Nepomichene, Thiery N J J; Tata, Etienne; Boyer, Sébastien

2015-12-01

Indoor spraying of insecticides and the use of insecticide-treated bed nets are key strategies for national malaria vector control in the central highlands of Madagascar. During the year 2013, malaria outbreaks were reported by the National Malaria Control Programme in the highlands, including the district of Ankazobe. Entomological trapping was carried out in April and May 2013 and in March 2014, using human landing catches, collection of mosquitoes resting in stables and in houses by oral aspirators, and Centers for Disease Control and Prevention light traps. Detection of Plasmodium in mosquitoes was carried out on head and thorax of anopheline females by ELISA, CSP and PCR (Plasmodium falciparum, Plasmodium malariae, Plasmodium vivax, or Plasmodium ovale). Human biting rate (HBR), sporozoite index and entomological infection rate (EIR) were calculated for Anopheles funestus, Anopheles arabiensis, Anopheles mascarensis, and Anopheles coustani. In Ankazobe district, the presence of malaria vectors such as An. funestus, An. arabiensis and An. mascarensis was confirmed, and a new and abundant potential vector, An. coustani was detected. Indeed, one individual of An. funestus and two An. coustani were detected positive with P. falciparum while one An. mascarensis and four An. coustani were positive with P. vivax. For An. coustani, in March 2014, the EIR varied from 0.01 infectious bites/person/month (ipm) outdoors to 0.11 ipm indoors. For An. funestus, in April 2013, the EIR was 0.13 ipm. The highest HBR value was observed for An. coustani, 86.13 ipm outdoors. The highest sporozoite rate was also for An. coustani, 9.5 % of An. coustani caught in stable was sporozoite positive. The implication of An. coustani in malaria transmission was not previously mentioned in Madagascar. Its very high abundance and the detection of Plasmodium coupled with an opportunistic feeding behaviour in villages with malaria cases supports its role in malaria transmission in Madagascar.

Lynch syndrome-associated extracolonic tumors are rare in two extended families with the same EPCAM deletion

NARCIS (Netherlands)

Lynch, H.T.; Riegert-Johnson, D.L.; Snyder, C.; Lynch, J.F.; Hagenkord, J.; Boland, C.R.; Rhees, J.; Thibodeau, S.N.; Boardman, L.A.; Davies, J.; Kuiper, R.P.; Hoogerbrugge, N.; Ligtenberg, M.J.L.

2011-01-01

OBJECTIVES: The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2. Some

Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk.

Science.gov (United States)

ten Broeke, Sanne W; Brohet, Richard M; Tops, Carli M; van der Klift, Heleen M; Velthuizen, Mary E; Bernstein, Inge; Capellá Munar, Gabriel; Gomez Garcia, Encarna; Hoogerbrugge, Nicoline; Letteboer, Tom G W; Menko, Fred H; Lindblom, Annika; Mensenkamp, Arjen R; Moller, Pal; van Os, Theo A; Rahner, Nils; Redeker, Bert J W; Sijmons, Rolf H; Spruijt, Liesbeth; Suerink, Manon; Vos, Yvonne J; Wagner, Anja; Hes, Frederik J; Vasen, Hans F; Nielsen, Maartje; Wijnen, Juul T

2015-02-01

The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks. © 2014 by American Society of Clinical Oncology.

Highly evolvable malaria vectors : The genomes of 16 Anopheles mosquitoes

NARCIS (Netherlands)

Neafsey, D. E.; Waterhouse, R. M.; Abai, M. R.; Aganezov, S. S.; Alekseyev, M. A.; Allen, J. E.; Amon, J.; Arca, B.; Arensburger, P.; Artemov, G.; Assour, L. A.; Basseri, H.; Berlin, A.; Birren, B. W.; Blandin, S. A.; Brockman, A. I.; Burkot, T. R.; Burt, A.; Chan, C. S.; Chauve, C.; Chiu, J. C.; Christensen, M.; Costantini, C.; Davidson, V. L. M.; Deligianni, E.; Dottorini, T.; Dritsou, V.; Gabriel, S. B.; Guelbeogo, W. M.; Hall, A. B.; Han, M. V.; Hlaing, T.; Hughes, D. S. T.; Jenkins, A. M.; Jiang, X.; Jungreis, I.; Kakani, E. G.; Kamali, M.; Kemppainen, P.; Kennedy, R. C.; Kirmitzoglou, I. K.; Koekemoer, L. L.; Laban, N.; Langridge, N.; Lawniczak, M. K. N.; Lirakis, M.; Lobo, N. F.; Lowy, E.; Maccallum, R. M.; Mao, C.; Maslen, G.; Mbogo, C.; Mccarthy, J.; Michel, K.; Mitchell, S. N.; Moore, W.; Murphy, K. A.; Naumenko, A. N.; Nolan, T.; Novoa, E. M.; O'loughlin, S.; Oringanje, C.; Oshaghi, M. A.; Pakpour, N.; Papathanos, P. A.; Peery, A. N.; Povelones, M.; Prakash, A.; Price, D. P.; Rajaraman, A.; Reimer, L. J.; Rinker, D. C.; Rokas, A.; Russell, T. L.; Sagnon, N.; Sharakhova, M. V.; Shea, T.; Simao, F. A.; Simard, F.; Slotman, M. A.; Somboon, P.; Stegniy, V.; Struchiner, C. J.; Thomas, G. W. C.; Tojo, M.; Topalis, P.; Tubio, J. M. C.; Unger, M. F.; Vontas, J.; Walton, C.; Wilding, C. S.; Willis, J. H.; Wu, Y.-c.; Yan, G.; Zdobnov, E. M.; Zhou, X.; Catteruccia, F.; Christophides, G. K.; Collins, F. H.; Cornman, R. S.; Crisanti, A.; Donnelly, M. J.; Emrich, S. J.; Fontaine, M. C.; Gelbart, W.; Hahn, M. W.; Hansen, I. A.; Howell, P. I.; Kafatos, F. C.; Kellis, M.; Lawson, D.; Louis, C.; Luckhart, S.; Muskavitch, M. A. T.; Ribeiro, J. M.; Riehle, M. A.; Sharakhov, I. V.; Tu, Z.; Zwiebel, L. J.; Besansky, N. J.

2015-01-01

Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16

Human biting activity, spatial-temporal distribution and malaria vector role of Anopheles calderoni in the southwest of Colombia.

Science.gov (United States)

Orjuela, Lorena I; Ahumada, Martha L; Avila, Ivonni; Herrera, Sócrates; Beier, John C; Quiñones, Martha L

2015-06-24

Anopheles calderoni was first recognized in Colombia in 2010 as this species had been misidentified as Anopheles punctimacula due to morphological similarities. An. calderoni is considered a malaria vector in Peru and has been found naturally infected with Plasmodium falciparum in Colombia. However, its biting behaviour, population dynamics and epidemiological importance have not been well described for Colombia. To assess the contribution of An. calderoni to malaria transmission and its human biting behaviour and spatial/temporal distribution in the southwest of Colombia, human landing catches (HLC) and larval collections were carried out in a cross-sectional, entomological study in 22 localities between 2011 and 2012, and a longitudinal study was performed in the Boca de Prieta locality in Olaya Herrera municipality between July 2012 and June 2013. All mosquitoes determined as An. calderoni were tested by ELISA to establish infection with Plasmodium spp. Larvae of An. calderoni were found in four localities in 12 out of 244 breeding sites inspected. An. calderoni adults were collected in 14 out of 22 localities during the cross-sectional study and represented 41.3% (459 of 1,111) of the collected adult specimens. Other species found were Anopheles albimanus (54.7%), Anopheles apicimacula (2.1%), Anopheles neivai (1.7%), and Anopheles argyritarsis (0.2%). In the localities that reported the highest malaria Annual Parasite Index (>10/1,000 inhabitants) during the year of sampling, An. calderoni was the predominant species (>90% of the specimens collected). In the longitudinal study, 1,528 An. calderoni were collected by HLC with highest biting rates in February, May and June 2013, periods of high precipitation. In general, the species showed a preference to bite outdoors (p Colombia. Its observed preference for outdoor biting is a major challenge for malaria control.

Sequencing and analysis of the complete mitochondrial genome in Anopheles sinensis (Diptera: Culicidae).

Science.gov (United States)

Chen, Kai; Wang, Yan; Li, Xiang-Yu; Peng, Heng; Ma, Ya-Jun

2017-10-02

Anopheles sinensis (Diptera: Culicidae) is a primary vector of Plasmodium vivax and Brugia malayi in most regions of China. In addition, its phylogenetic relationship with the cryptic species of the Hyrcanus Group is complex and remains unresolved. Mitochondrial genome sequences are widely used as molecular markers for phylogenetic studies of mosquito species complexes, of which mitochondrial genome data of An. sinensis is not available. An. sinensis samples was collected from Shandong, China, and identified by molecular marker. Genomic DNA was extracted, followed by the Illumina sequencing. Two complete mitochondrial genomes were assembled and annotated using the mitochondrial genome of An. gambiae as reference. The mitochondrial genomes sequences of the 28 known Anopheles species were aligned and reconstructed phylogenetic tree by Maximum Likelihood (ML) method. The length of complete mitochondrial genomes of An. sinensis was 15,076 bp and 15,138 bp, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and an AT-rich control region. As in other insects, most mitochondrial genes are encoded on the J strand, except for ND5, ND4, ND4L, ND1, two rRNA and eight tRNA genes, which are encoded on the N strand. The bootstrap value was set as 1000 in ML analyses. The topologies restored phylogenetic affinity within subfamily Anophelinae. The ML tree showed four major clades, corresponding to the subgenera Cellia, Anopheles, Nyssorhynchus and Kerteszia of the genus Anopheles. The complete mitochondrial genomes of An. sinensis were obtained. The number, order and transcription direction of An. sinensis mitochondrial genes were the same as in other species of family Culicidae.

Cell cycle–related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients

Science.gov (United States)

Chen, Jinyun; Pande, Mala

2013-01-01

Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle–related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle–related genes and 31 DNA repair–related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan–Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P Lynch syndrome. PMID:23125224

Cell cycle-related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients.

Science.gov (United States)

Chen, Jinyun; Pande, Mala; Huang, Yu-Jing; Wei, Chongjuan; Amos, Christopher I; Talseth-Palmer, Bente A; Meldrum, Cliff J; Chen, Wei V; Gorlov, Ivan P; Lynch, Patrick M; Scott, Rodney J; Frazier, Marsha L

2013-02-01

Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle-related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle-related genes and 31 DNA repair-related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan-Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P Lynch syndrome.

Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability

OpenAIRE

Umar, Asad; Boland, C. Richard; Terdiman, Jonathan P.; Syngal, Sapna; de la Chapelle, Albert; Rüschoff, Josef; Fishel, Richard; Lindor, Noralane M.; Burgart, Lawrence J.; Hamelin, Richard; Hamilton, Stanley R.; Hiatt, Robert A.; Jass, Jeremy; Lindblom, Annika; Lynch, Henry T.

2004-01-01

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Because cancers with MSI account for approximately 15% of all colorectal cancers and because of the need for a better understanding of the clinical and histologic manifestations of HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in 1996, which led to...

Chemical Composition and Repellent Activity of Achillea vermiculata and Satureja hortensis against Anopheles stephensi

Directory of Open Access Journals (Sweden)

Masoumeh Pirmohammadi

2016-01-01

Full Text Available Background: One of the best ways to control the malaria disease and to be protected human against Anopheles mos­quito biting is the use of repellents. Throughout repellents, herbal ones may be an appropriate and safe source for protection.Methods: Chemical constituents of Achillea vermiculata and Satoreja hortensis were determined by using gas chromatography-mass spectrometry. Efficacy and the protection time of these plants were assessed on Anopheles stephensi under the laboratory condition.Results: The mean assessed protection time and efficacy for A. vermiculata was 2.16 and 3.16 hours respectively and the obtained ED50 and ED90 for this plant was 5.67 and 63 µl/cm2 respectively. The figured for S. hortensis was 4.16 and 5 hours respectively.  ED50 and ED90 for this plant were 5.63 and 45.75µl/cm2 respectively.Conclusion: Results of investigation showed that S. hortensis plant has an acceptable protection time, therefore, this plant could be considered as a good herbal repellent against anopheles mosquitoes.

Subtotal Colectomy for Colon Cancer Reduces the Need for Subsequent Surgery in Lynch Syndrome.

Science.gov (United States)

Renkonen-Sinisalo, Laura; Seppälä, Toni T; Järvinen, Heikki J; Mecklin, Jukka-Pekka

2017-08-01

The risk of metachronous colorectal cancer is high after surgical resection for first colon cancer in Lynch syndrome. This study aimed to examine whether extended surgery decreases the risk of subsequent colorectal cancer and improves long-term survival. This was a retrospective study. Data were collected from a nationwide registry. Two hundred forty-two Lynch syndrome pathogenic variant carriers who underwent surgery for a first colon cancer from 1984 to 2009 were included. Patients underwent standard segmental colectomy (n = 144) or extended colectomy (n = 98) for colon cancer. Patients were followed a median of 14.6 up to 25 years. Risk of subsequent colorectal cancer in either group, overall and disease-specific survival, and operative mortality were the primary outcomes measured. Subtotal colectomy decreased the risk of subsequent colorectal cancer (HR, 0.20; 95% CI, 0.08-0.52; p = 0.001), compared with segmental resection. Subsequent colorectal cancer decreased in MLH1 carriers. The MSH2 carriers showed no statistical difference, possibly because of their small number. Disease-specific and overall survival within 25 years did not differ between the standard and extended surgeries (82.7% vs 87.2%, p = 0.76 and 47.2% vs 41.4%, p = 0.83). The cumulative risk of subsequent colorectal cancer was 20% in 10 years and 47% within 25 years after standard resection and 4% and 9% after extended surgery. The cumulative risk of metachronous colorectal cancer was 7% within 25 years after subtotal colectomy with ileosigmoidal anastomosis. One patient died of postoperative septicemia within 30 days after segmental colectomy. Data on surgical procedures were primarily collected retrospectively. Lynch syndrome pathogenic variant carriers may undergo subtotal colectomy to manage first colon cancer and avoid repetitive abdominal surgery and to reduce the remaining bowel to facilitate easier endoscopic surveillance. It provides no survival benefit, compared with segmental colon

Mutation spectrum and risk of colorectal cancer in African American families with Lynch syndrome.

Science.gov (United States)

Guindalini, Rodrigo Santa Cruz; Win, Aung Ko; Gulden, Cassandra; Lindor, Noralane M; Newcomb, Polly A; Haile, Robert W; Raymond, Victoria; Stoffel, Elena; Hall, Michael; Llor, Xavier; Ukaegbu, Chinedu I; Solomon, Ilana; Weitzel, Jeffrey; Kalady, Matthew; Blanco, Amie; Terdiman, Jonathan; Shuttlesworth, Gladis A; Lynch, Patrick M; Hampel, Heather; Lynch, Henry T; Jenkins, Mark A; Olopade, Olufunmilayo I; Kupfer, Sonia S

2015-11-01

African Americans (AAs) have the highest incidence of and mortality resulting from colorectal cancer (CRC) in the United States. Few data are available on genetic and nongenetic risk factors for CRC among AAs. Little is known about cancer risks and mutations in mismatch repair (MMR) genes in AAs with the most common inherited CRC condition, Lynch syndrome. We aimed to characterize phenotype, mutation spectrum, and risk of CRC in AAs with Lynch syndrome. We performed a retrospective study of AAs with mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referral centers. We analyzed data on personal and family histories of cancer. Modified segregation analysis conditioned on ascertainment criteria was used to estimate age- and sex-specific CRC cumulative risk, studying members of the mutation-carrying families. We identified 51 AA families with deleterious mutations that disrupt function of the MMR gene product: 31 in MLH1 (61%), 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutations were detected in more than 1 individual, and 11 have not been previously reported. In the 920 members of the 51 families with deleterious mutations, the cumulative risks of CRC at 80 years of age were estimated to be 36.2% (95% confidence interval [CI], 10.5%-83.9%) for men and 29.7% (95% CI, 8.31%-76.1%) for women. CRC risk was significantly higher among individuals with mutations in MLH1 or MSH2 (hazard ratio, 13.9; 95% CI, 3.44-56.5). We estimate the cumulative risk for CRC in AAs with MMR gene mutations to be similar to that of individuals of European descent with Lynch syndrome. Two-thirds of mutations were found in MLH1, some of which were found in multiple individuals and some that have not been previously reported. Differences in mutation spectrum are likely to reflect the genetic diversity of this population. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

The effect of physical water quality and water level changes on the occurrence and density of Anopheles mosquito larvae around the shoreline of the Koka reservoir, central Ethiopia

Directory of Open Access Journals (Sweden)

S. Kibret

2010-12-01

Full Text Available Entomological studies to determine the effect of the physical characteristics of mosquito larval breeding water bodies and reservoir water level changes on the occurrence of Anopheles mosquito larvae were conducted in two villages at Koka reservoir in central Ethiopia between August and December 2007. Of the two study villages, Ejersa is located close to the reservoir, and Kuma is 5 km away from it. Data on the type, number and physical characteristics of Anopheles larval breeding habitat, species composition and densities of anopheles mosquitoes in and around the study villages were investigated and recorded. Meteorological and reservoir water level data were compared with availability of Anopheles larval breeding sites and densities. Entomological data, derived from weekly larval collections, showed that Anopheles pharoensis Theobald, Anopheles gambiae s.l. Giles, Anopheles coustani Laveran and Anopheles squamosus Theobald were breeding in the study area. The mean larval density of An. gambiae s.l. in this study was higher in slightly turbid and shallow aquatic habitat than in turbid and relatively deep aquatic habitat. The density of An. pharoensis in habitat with floating vegetation and with relatively shady conditions was significantly higher than that of less shaded aquatic habitat and greater emergent vegetation. There was also a positive correlation between the occurrence of Anopheles larvae with the water and daily minimum atmospheric temperature. Similarly at Ejersa, over the sampling period, there was a positive correlation between falling reservoir water levels and the number of positive breeding habitats. These results confirm that physical characteristics of the water bodies play an important role in the species composition, total Anopheles larval count, and the density of Anopheles mosquitoes. Suitable breeding habitat in the vicinity of the reservoir village was strongly associated with the reservoir. This is particularly

Explaining variation in adult Anopheles indoor resting abundance: the relative effects of larval habitat proximity and insecticide-treated bed net use.

Science.gov (United States)

McCann, Robert S; Messina, Joseph P; MacFarlane, David W; Bayoh, M Nabie; Gimnig, John E; Giorgi, Emanuele; Walker, Edward D

2017-07-17

Spatial determinants of malaria risk within communities are associated with heterogeneity of exposure to vector mosquitoes. The abundance of adult malaria vectors inside people's houses, where most transmission takes place, should be associated with several factors: proximity of houses to larval habitats, structural characteristics of houses, indoor use of vector control tools containing insecticides, and human behavioural and environmental factors in and near houses. While most previous studies have assessed the association of larval habitat proximity in landscapes with relatively low densities of larval habitats, in this study these relationships were analysed in a region of rural, lowland western Kenya with high larval habitat density. 525 houses were sampled for indoor-resting mosquitoes across an 8 by 8 km study area using the pyrethrum spray catch method. A predictive model of larval habitat location in this landscape, previously verified, provided derivations of indices of larval habitat proximity to houses. Using geostatistical regression models, the association of larval habitat proximity, long-lasting insecticidal nets (LLIN) use, house structural characteristics (wall type, roof type), and peridomestic variables (cooking in the house, cattle near the house, number of people sleeping in the house) with mosquito abundance in houses was quantified. Vector abundance was low (mean, 1.1 adult Anopheles per house). Proximity of larval habitats was a strong predictor of Anopheles abundance. Houses without an LLIN had more female Anopheles gambiae s.s., Anopheles arabiensis and Anopheles funestus than houses where some people used an LLIN (rate ratios, 95% CI 0.87, 0.85-0.89; 0.84, 0.82-0.86; 0.38, 0.37-0.40) and houses where everyone used an LLIN (RR, 95% CI 0.49, 0.48-0.50; 0.39, 0.39-0.40; 0.60, 0.58-0.61). Cooking in the house also reduced Anopheles abundance across all species. The number of people sleeping in the house, presence of cattle near the house

Vector Competence of Anopheles kleini and Anopheles sinensis (Diptera: Culicidae) From the Republic of Korea to Vivax Malaria-Infected Blood From Patients From Thailand.

Science.gov (United States)

Ubalee, Ratawan; Kim, Heung-Chul; Schuster, Anthony L; McCardle, Patrick W; Phasomkusolsil, Siriporn; Takhampunya, Ratree; Davidson, Silas A; Lee, Won-Ja; Klein, Terry A

2016-11-01

In total, 1,300 each of Anopheles kleini Rueda and Anopheles sinensis Wiedemann sensu stricto (s.s.) females (colonized from the Republic of Korea) and Anopheles dirus Peyton & Harrison (Thai strain) were allowed to feed on blood from Thai malaria patients naturally infected with Plasmodium vivax The overall oocyst infection rates for An. dirus, An. kleini, and An. sinensis s.s. were 77.4, 46.1, and 45.9%, respectively. The mean number of oocysts was significantly higher for An. dirus (82.7) compared with An. kleini (6.1) and An. sinensis s.s. (8.6), whereas the mean number of oocysts for An. kleini and An. sinensis s.s. was similar. The overall sporozoite infection rates for An. dirus, An. kleini, and An. sinensis s.s. dissected on days 14-15, 21, and 28 days post-feed were significantly higher for An. dirus (90.0%) than An. kleini (5.4%), whereas An. kleini sporozoite rates were significantly higher than An. sinensis s.s. (1,000 sporozoites) salivary gland indices were significantly higher for An. dirus (85.7%), compared with An. kleini (47.1%). Only one An. sinensis s.s. had sporozoites (+2; >10-100 sporozoites). These results indicate that An. kleini is a competent vector of vivax malaria. Although An. sinensis s.s. develops relatively high numbers of oocysts, it is considered a very poor vector of vivax malaria due to a salivary gland barrier. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.

Genetic anticipation in Swedish Lynch syndrome families

DEFF Research Database (Denmark)

von Salomé, Jenny; Boonstra, Philip S; Karimi, Masoud

2017-01-01

Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS) caused by mutations in DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have......-2013. We analyzed a homogenous group of mutation carriers, utilizing information from both affected and non-affected family members. In total, 239 families with a mismatch repair gene mutation (96 MLH1 families, 90 MSH2 families including one family with an EPCAM-MSH2 deletion, 39 MSH6 families, 12 PMS2...... families, and 2 MLH1+PMS2 families) comprising 1028 at-risk carriers were identified among the Swedish LS families, of which 1003 mutation carriers had available follow-up information and could be included in the study. Using a normal random effects model (NREM) we estimate a 2.1 year decrease in age...

Vectorial status and insecticide resistance of Anopheles funestus from a sugar estate in southern Mozambique.

Science.gov (United States)

Kloke, R Graham; Nhamahanga, Eduardo; Hunt, Richard H; Coetzee, Maureen

2011-02-09

The dual problems of rising insecticide resistance in the malaria vectors and increasing human malaria cases since 2001 in southern Mozambique are cause for serious concern. The selection of insecticides for use in indoor residual spraying (IRS) programmes is highly dependent on the extent to which local mosquitoes are susceptible to the approved classes of insecticides. The insecticide resistance status and role in malaria transmission of Anopheles funestus was evaluated at the Maragra Sugar Estate in southern Mozambique where an IRS vector control programme has been in operation for seven years using the carbamate insecticide bendiocarb. No Anopheles species were captured inside the sugar estate control area. Anopheles funestus group captured outside of the estate represented 90% (n = 475) of the total collections. Of the specimens identified to species by PCR (n = 167), 95% were An. funestus s.s. One An. rivulorum was identified and seven specimens did not amplify. The Anopheles gambiae complex was less abundant (n = 53) and of those identified (n = 33) 76% were An. arabiensis and 24% An. merus. Insecticide susceptibility tests showed that wild-caught and F-1 family An. funestus were resistant to deltamethrin (32.5% mortality) and lambda-cyhalothrin (14.6% mortality), less so to bendiocarb (71.5% mortality) and fully susceptible to both malathion and DDT (100%). Bendiocarb and pyrethroid resistance was nullified using 4% piperonyl butoxide (Pbo), strongly suggesting that both are mediated by P450 monooxygenase detoxification. ELISA tests of An. funestus for Plasmodium falciparum, gave a sporozoite rate of 6.02% (n = 166). One unidentified member of the An. gambiae complex tested positive for P. falciparum sporozoites. Anopheles funestus was found to be the most abundant and principle vector of malaria in this area, with members of the An. gambiae complex being secondary vectors. Despite the continual use of bendiocarb within the estate for seven years and the

Vectorial status and insecticide resistance of Anopheles funestus from a sugar estate in southern Mozambique

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Nhamahanga Eduardo

2011-02-01

Full Text Available Abstract Background The dual problems of rising insecticide resistance in the malaria vectors and increasing human malaria cases since 2001 in southern Mozambique are cause for serious concern. The selection of insecticides for use in indoor residual spraying (IRS programmes is highly dependent on the extent to which local mosquitoes are susceptible to the approved classes of insecticides. The insecticide resistance status and role in malaria transmission of Anopheles funestus was evaluated at the Maragra Sugar Estate in southern Mozambique where an IRS vector control programme has been in operation for seven years using the carbamate insecticide bendiocarb. Results No Anopheles species were captured inside the sugar estate control area. Anopheles funestus group captured outside of the estate represented 90% (n = 475 of the total collections. Of the specimens identified to species by PCR (n = 167, 95% were An. funestus s.s. One An. rivulorum was identified and seven specimens did not amplify. The Anopheles gambiae complex was less abundant (n = 53 and of those identified (n = 33 76% were An. arabiensis and 24% An. merus. Insecticide susceptibility tests showed that wild-caught and F-1 family An. funestus were resistant to deltamethrin (32.5% mortality and lambda-cyhalothrin (14.6% mortality, less so to bendiocarb (71.5% mortality and fully susceptible to both malathion and DDT (100%. Bendiocarb and pyrethroid resistance was nullified using 4% piperonyl butoxide (Pbo, strongly suggesting that both are mediated by P450 monooxygenase detoxification. ELISA tests of An. funestus for Plasmodium falciparum, gave a sporozoite rate of 6.02% (n = 166. One unidentified member of the An. gambiae complex tested positive for P. falciparum sporozoites. Conclusion Anopheles funestus was found to be the most abundant and principle vector of malaria in this area, with members of the An. gambiae complex being secondary vectors. Despite the continual use of

Distribution of the species of the Anopheles gambiae complex and first evidence of Anopheles merus as a malaria vector in Madagascar

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Le Goff Gilbert

2003-10-01

Full Text Available Abstract Background Members of the Anopheles gambiae complex are amongst the best malaria vectors in the world, but their vectorial capacities vary between species and populations. A large-scale sampling of An. gambiae sensu lato was carried out in various bioclimatic domains of Madagascar. Local abundance of an unexpected member of this complex raised questions regarding its role in malaria transmission. Methods Sampling took place at 38 sites and 2,067 females were collected. Species assessment was performed using a PCR targeting a sequence in the IGS of the rDNA. Analysis focused on the relative prevalence of the species per site, bioclimatic domain and altitude. Infectivity of Anopheles merus was assessed using an ELISA to detect the presence of malarial circumsporozoite protein in the head-thorax. Results Three species were identified: An. gambiae, Anopheles arabiensis and An. merus. The distribution of each species is mainly a function of bioclimatic domains and, to a lesser extent, altitude. An. arabiensis is present in all bioclimatic domains with highest prevalence in sub-humid, dry and sub-arid domains. An. gambiae has its highest prevalence in the humid domain, is in the minority in dry areas, rare in sub-humid and absent in sub-arid domains. An. merus is restricted to the coastal fringe in the south and west; it was in the majority in one southern village. The majority of sites were sympatric for at least two of the species (21/38 and two sites harboured all three species. The role of An. merus as malaria vector was confirmed in the case of two human-biting females, which were ELISA-positive for Plasmodium falciparum. Conclusion Despite the huge environmental (mainly man-made changes in Madagascar, the distribution of An. gambiae and An. arabiensis appears unchanged for the past 35 years. The distribution of An. merus is wider than was previously known, and its effectiveness as a malaria vector has been shown for the first time; this

Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome

OpenAIRE

Serracant Barrera, Anna; Serra Pla, Sheila; Blázquez Maña, Carmen María; Salas, Rubén Carrera; García Monforte, Neus; Bejarano González, Natalia; Romaguera Monzonis, Andreu; Andreu Navarro, Francisco Javier; Bella Cueto, Maria Rosa; Borobia, Francisco G.

2017-01-01

Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and seboma...

Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling.

Science.gov (United States)

Johnatty, Sharon E; Tan, Yen Y; Buchanan, Daniel D; Bowman, Michael; Walters, Rhiannon J; Obermair, Andreas; Quinn, Michael A; Blomfield, Penelope B; Brand, Alison; Leung, Yee; Oehler, Martin K; Kirk, Judy A; O'Mara, Tracy A; Webb, Penelope M; Spurdle, Amanda B

2017-11-01

To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10 -7 ), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (P Trend =4.43×10 -6 ), and with increasing numbers of Lynch cancers in relatives (P Trend ≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Screening for adulticidal bioactivity of South African plants against Anopheles arabiensis

CSIR Research Space (South Africa)

Maharaj, R

2011-08-01

Full Text Available of Corymbia citriodora (Myrtaceae), and leaves and seeds of both Ocimum kilimandscharicum and Ocimum suave (Lamiaceae) had exhibited a signifi- cant repellent effect against Anopheles gambiae s.s and An. arabiensis during application of plant material...

Towards gene-and gender-based risk estimates in Lynch syndrome; Age-specific incidences for 13 extra-colorectal cancer types

DEFF Research Database (Denmark)

Therkildsen, Christina; Ladelund, Steen; Smith-Hansen, Lars

2017-01-01

Background:In Lynch syndrome, inherited mismatch repair (MMR) defects predispose to colorectal cancer and to a wide spectrum of extra-colorectal tumours. Utilising a cohort study design, we aimed to determine the risk of extra-colorectal cancer and to identify yet unrecognised tumour types...... were identified for 13 cancer types with differences related to gender, age and disease-predisposing gene. The different cancer types showed variable peak age incidence rates (IRs) with the highest IRs for ovarian cancer at age 30-49 years, for endometrial cancer, breast cancer, renal cell cancer...... and brain tumours at age 50-69 years, and for urothelial cancer, small bowel cancer, gastric cancer, pancreatic cancer and skin tumours after age 70.Conclusions:The broad spectrum of tumour types that develop at an increased incidence defines Lynch syndrome as a multi-tumour syndrome. The variable...

Effect of larval crowding on mating competitiveness of Anopheles gambiae mosquitoes

NARCIS (Netherlands)

Ng'habi, K.R.; John, B.; Nkwengulila, G.; Knols, B.G.J.; Killeen, G.F.; Ferguson, H.M.

2005-01-01

Background: The success of sterile or transgenic Anopheles for malaria control depends on their mating competitiveness within wild populations. Current evidence suggests that transgenic mosquitoes have reduced fitness. One means of compensating for this fitness deficit would be to identify

MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer.

Science.gov (United States)

Talseth-Palmer, Bente A; McPhillips, Mary; Groombridge, Claire; Spigelman, Allan; Scott, Rodney J

2010-05-21

Approximately 10% of Lynch syndrome families have a mutation in MSH6 and fewer families have a mutation in PMS2. It is assumed that the cancer incidence is the same in families with mutations in MSH6 as in families with mutations in MLH1/MSH2 but that the disease tends to occur later in life, little is known about families with PMS2 mutations. This study reports on our findings on mutation type, cancer risk and age of diagnosis in MSH6 and PMS2 families. A total of 78 participants (from 29 families) with a mutation in MSH6 and 7 participants (from 6 families) with a mutation in PMS2 were included in the current study. A database of de-identified patient information was analysed to extract all relevant information such as mutation type, cancer incidence, age of diagnosis and cancer type in this Lynch syndrome cohort. Cumulative lifetime risk was calculated utilising Kaplan-Meier survival analysis. MSH6 and PMS2 mutations represent 10.3% and 1.9%, respectively, of the pathogenic mutations in our Australian Lynch syndrome families. We identified 26 different MSH6 and 4 different PMS2 mutations in the 35 families studied. We report 15 novel MSH6 and 1 novel PMS2 mutations. The estimated cumulative risk of CRC at age 70 years was 61% (similar in males and females) and 65% for endometrial cancer in MSH6 mutation carriers. The risk of developing CRC is different between males and females at age 50 years, which is 34% for males and 21% for females. Novel MSH6 and PMS2 mutations are being reported and submitted to the current databases for identified Lynch syndrome mutations. Our data provides additional information to add to the genotype-phenotype spectrum for both MSH6 and PMS2 mutations.

Spatial distribution and habitat characterisation of Anopheles larvae along the Kenyan coast.

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Mwangangi, Joseph M; Mbogo, Charles M; Muturi, Ephantus J; Nzovu, Joseph G; Githure, John I; Yan, Guiyun; Minakawa, Noboru; Novak, Robert; Beier, John C

2007-03-01

A study was conducted to characterise larval habitats and to determine spatial heterogeneity of the Anopheles mosquito larvae. The study was conducted from May to June 1999 in nine villages along the Kenyan coast. Aquatic habitats were sampled by use of standard dipping technique. The habitats were characterised based on size, pH, distance to the nearest house, coverage of canopy, surface debris, algae and emergent plants, turbidity, substrate, and habitat type. A total of 110 aquatic habitats like stream pools (n=10); puddles (n=65); tire tracks (n=5); ponds (n=5) and swamps (n=25) were sampled in nine villages located in three districts of the Kenyan coast. A total of 7,263 Anopheles mosquito larvae were collected, 63.9% were early instars and 36.1% were late instars. Morphological identification of the III and IV instar larvae by use of microscopy yielded 90.66% (n=2377) Anopheles gambiae Complex, 0.88% (n=23) An. funestus, An. coustani 7.63% (n=200), An. rivulorum 0.42% (n=11), An. pharoensis 0.19% (n=5), An. swahilicus 0.08% (n=2), An. wilsoni 0.04% (n=1) and 0.11% (n=3) were unidentified. A subset of the An. gambiae Complex larvae identified morphologically, was further analysed using rDNA-PCR technique resulting in 68.22% (n=1290) An. gambiae s.s., 7.93% (n=150) An. arabiensis and 23.85% (n=451) An. merus. Multiple logistic regression model showed that emergent plants (p = 0.019), and floating debris (p = 0.038) were the best predictors of An. gambiae larval abundance in these habitats. Habitat type, floating debris and emergent plants were found to be the key factors determining the presence of Anopheles larvae in the habitats. For effective larval control, the type of habitat should be considered and most productive habitat type be given a priority in the mosquito abatement programme.

Considerations and management of a patient with three metachronous cancers in association with Lynch syndrome and ileal Crohn’s disease: A case report

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Kaleb Lourensz

2015-01-01

Conclusion: The surgical treatment of patients with Lynch syndrome requires a sound knowledge of the possible neoplastic conditions that can arise in the syndrome. Early detection is paramount, either by implementation of evidence based surveillance programs or at least by a heightened clinical awareness of the features of this disease. Ideally this will result in both reduced surgical morbidity and improved oncologic outcome. Furthermore, the medical treatment of Crohn’s disease in a patient with tumors arising from Lynch syndrome must be undertaken with at least a consideration of the possibility that the use of immunosuppressive medication might increase the risk of cancer recurrence.

Validation of a Self-Concept Scale for Lynch Syndrome in Different Nationalities

DEFF Research Database (Denmark)

Petersen, Helle Vendel; Domanska, Katarina; Bendahl, Pär-Ola

2011-01-01

syndrome. We compared the performance of this scale in 591 mutation carriers from Denmark, Sweden and Canada. Principal component analysis identified two sets of linked statements-the first related to feeling different, isolated and labeled, and the second to concern and worry about bowel changes....... The scale performed consistently in the three countries. Minor differences were identified, with guilt about passing on a defective gene and feelings of losing one's privacy being more pronounced among Canadians, whereas Danes more often expressed worries about cancer. Validation of the Lynch syndrome self...

Screening adherence and cancer risk perceptions in colorectal cancer survivors with Lynch-like syndrome.

Science.gov (United States)

Katz, L H; Burton-Chase, A M; Advani, S; Fellman, B; Polivka, K M; Yuan, Y; Lynch, P M; Peterson, S K

2016-03-01

Cancer screening recommendations for patients with Lynch-like syndrome (LLS) are not well defined. We evaluated adherence to Lynch syndrome (LS) screening recommendations, cancer risk perceptions, and communication within the families among colorectal cancer (CRC) survivors with LLS. Thirty-four participants with LLS completed a questionnaire about risk perception, adherence to LS screening recommendations, and communication with relatives. Clinical data were obtained from medical records. Most participants (76%) believed they should undergo colonoscopy every 1-2 years. Only 41% correctly interpreted their genetic tests as uninformative negative or as variant of unknown significance for LS. Less than half had had an upper gastrointestinal endoscopy for screening purpose. Among female participants, 86% had been screened for endometrial cancer (EC) and 71% for ovarian cancer. Most participants had informed relatives about the CRC diagnosis and advised them to undergo CRC screening, but only 50% advised female relatives to be screened for EC and only one-third advised relatives to have genetic counseling. Most CRC survivors with LLS follow the same cancer screening recommended for LS patients but do not understand the meaning of LLS. Greater care must be devoted to communicating the implications of nondiagnostic germline mutation testing among patients with LLS. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Laboratory evolution of the entomopathogenic fungus Beauveria bassiana against Anopheles stephensi larvae (Diptera: Culicidae

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Rahele Veys-Behbahani

2014-09-01

Full Text Available Objective: To examine Beauveria bassiana (B. bassiana fungus bioassay against the larval stages of Anopheles stephensi in Iran. Methods: The fungal suspension by the concentrations of 1伊1 09, 5伊1 08, 1 08, 5伊1 07 and 1伊 107 conidia per milliliter have been prepared in different volumes (2, 4 and 6 mL and each concentration were added to containers containing 25 Anopheles larva instars 1 and 2. The mortality of the dead larvae with abnormal symptoms was recorded as a result of the fungal infection after 24, 48 and 72 h. Results: Comparison between the mean mortality rate of Anopheles stephensi larva at different concentrations of B. bassiana strain Iran 429C at 2, 4 and 6 mL showed that there was no significant relation of the mean mortality rate of larvae at concentrations of 1伊109 and 5伊108, and after 48 h resulted in 100% mortality rate of the larvae populations. In addition, there is no significant differences in the amounts of lethal times (LT (LT50 and LT90 as LT90 values calculated at a concentration of 5伊108 and in volumes 2, 4 and 6 mL were 1.46, 1.36 and 1.08 d, respectively. Conclusions: B. bassiana strain Iran 429C in 2 mL of 5伊108 concentration or the concentration of a 1伊109 mL per 100 mL of water is recommended as the optimal concentration for the control of Anopheles larvae. The development of suitable formulations of entomopathogenic fungi may be a promising prospect in the mosquito control programs.

Ability of TEP1 in intestinal flora to modulate natural resistance of Anopheles dirus.

Science.gov (United States)

Wang, Yanyan; Wang, Ying; Zhang, Jingru; Xu, Wenyue; Zhang, Jian; Huang, Fu Sheng

2013-08-01

Blocking transmission of malaria is a reliable way to control and eliminate infection. However, in-depth knowledge of the interaction between Plasmodium and mosquito is needed. Studies suggest that innate immunity is the main mechanism inhibiting development of malaria parasites in the mosquito. Recent studies have found that use of antibiotics that inhibit the mosquito gut flora can reduce the immune response of Anopheles gambiae, thereby contributing to the development of malaria parasites. In our study, we used the non susceptible model of Anopheles dirus-Plasmodium yoelii to explore the effect of Anopheles intestinal flora on the natural resistance of A. dirus to P. yoelii. We found that in mosquitoes infected with Plasmodium, the intestinal flora can regulate expression of thioester-containing protein (TEP1) via an RNAi gene-silencing approach. Our results suggest that in the absence of TEP1, the natural microbiota cannot suppress the development of P. yoelii in A. dirus. This suggests that AdTEP1 plays an important role in the resistance of A. dirus to P. yoelii. The intestinal flora may modulate the development of P. yoelii in A. dirus by regulating TEP1 expression. Copyright © 2013 Elsevier Inc. All rights reserved.

Anopheles moucheti and Anopheles vinckei are candidate vectors of ape Plasmodium parasites, including Plasmodium praefalciparum in Gabon.

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Christophe Paupy

Full Text Available During the last four years, knowledge about the diversity of Plasmodium species in African great apes has considerably increased. Several new species were described in chimpanzees and gorillas, and some species that were previously considered as strictly of human interest were found to be infecting African apes. The description in gorillas of P. praefalciparum, the closest relative of P. falciparum which is the main malignant agent of human malaria, definitively changed the way we understand the evolution and origin of P. falciparum. This parasite is now considered to have appeared recently, following a cross-species transfer from gorillas to humans. However, the Plasmodium vector mosquito species that have served as bridge between these two host species remain unknown. In order to identify the vectors that ensure ape Plasmodium transmission and evaluate the risk of transfer of these parasites to humans, we carried out a field study in Gabon to capture Anopheles in areas where wild and semi-wild ape populations live. We collected 1070 Anopheles females belonging to 15 species, among which An. carnevalei, An. moucheti and An. marshallii were the most common species. Using mtDNA-based PCR tools, we discovered that An. moucheti, a major human malaria vector in Central Africa, could also ensure the natural transmission of P. praefalciparum among great apes. We also showed that, together with An. vinckei, An. moucheti was infected with P. vivax-like parasites. An. moucheti constitutes, therefore, a major candidate for the transfer of Plasmodium parasites from apes to humans.

Efficacy of bifenthrin-impregnated bednets against Anopheles funestus and pyrethroid-resistant Anopheles gambiae in North Cameroon

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Chouaibou Mouhamadou

2006-09-01

Full Text Available Abstract Background Recent field studies indicated that insecticide-treated bednets (ITNs maintain their efficacy despite a high frequency of the knock-down resistance (kdr gene in Anopheles gambiae populations. It was essential to evaluate ITNs efficacy in areas with metabolic-based resistance. Methods Bifenthrin was used in this experiment because it is considered a promising candidate for bednets impregnation. Nets were treated at 50 mg/m2, a dose that has high insecticidal activity on kdr mosquitoes and at 5 mg/m2, a dose that kills 95% of susceptible mosquitoes under laboratory conditions with 3 minutes exposure. Bednets were holed to mimic physical damage. The trial was conducted in three experimental huts from Pitoa, North-Cameroon where Anopheles gambiae displays metabolic resistance and cohabits with An. funestus. Results Bifenthrin at 50 mg/m2 significantly reduced anophelines' entry rate (>80%. This was not observed at 5 mg/m2. Both treatments increased exophily in An. gambiae, and to a lesser extent in An. funestus. With bifenthrin at high dosage, over 60% reduction in blood feeding and 75–90% mortality rates were observed in both vectors. Despite presence of holes, only a single An. gambiae and two An. funestus females were collected inside the treated net, and all were found dead. The same trends were observed with low dosage bifenthrin though in most cases, no significant difference was found with the untreated control net. Conclusion Bifenthrin-impregnated bednets at 50 mg/m2 were efficient in the reduction of human-vector contact in Pitoa. Considerable personal protection was gained against An. funestus and metabolic pyrethroid resistant An. gambiae populations.

Efficacy of bifenthrin-impregnated bednets against Anopheles funestus and pyrethroid-resistant Anopheles gambiae in North Cameroon

Science.gov (United States)

Chouaibou, Mouhamadou; Simard, Frédéric; Chandre, Fabrice; Etang, Josiane; Darriet, Frédéric; Hougard, Jean-Marc

2006-01-01

Background Recent field studies indicated that insecticide-treated bednets (ITNs) maintain their efficacy despite a high frequency of the knock-down resistance (kdr) gene in Anopheles gambiae populations. It was essential to evaluate ITNs efficacy in areas with metabolic-based resistance. Methods Bifenthrin was used in this experiment because it is considered a promising candidate for bednets impregnation. Nets were treated at 50 mg/m2, a dose that has high insecticidal activity on kdr mosquitoes and at 5 mg/m2, a dose that kills 95% of susceptible mosquitoes under laboratory conditions with 3 minutes exposure. Bednets were holed to mimic physical damage. The trial was conducted in three experimental huts from Pitoa, North-Cameroon where Anopheles gambiae displays metabolic resistance and cohabits with An. funestus. Results Bifenthrin at 50 mg/m2 significantly reduced anophelines' entry rate (>80%). This was not observed at 5 mg/m2. Both treatments increased exophily in An. gambiae, and to a lesser extent in An. funestus. With bifenthrin at high dosage, over 60% reduction in blood feeding and 75–90% mortality rates were observed in both vectors. Despite presence of holes, only a single An. gambiae and two An. funestus females were collected inside the treated net, and all were found dead. The same trends were observed with low dosage bifenthrin though in most cases, no significant difference was found with the untreated control net. Conclusion Bifenthrin-impregnated bednets at 50 mg/m2 were efficient in the reduction of human-vector contact in Pitoa. Considerable personal protection was gained against An. funestus and metabolic pyrethroid resistant An. gambiae populations. PMID:16961938

Larvicidal activity of Zanthoxylum acanthopodium essential oil against the malaria mosquitoes, Anopheles anthropophagus and Anopheles sinensis.

Science.gov (United States)

He, Qi; Wang, Wenxia; Zhu, Liang

2018-05-15

Zanthoxylum acanthopodium has insecticidal effect in Chinese traditional medicine. In this study, the essential oil from the dried Zanthoxylum plant was used as a larvicidal compound against the malaria mosquitoes, Anopheles anthropophagus and Anopheles sinensis. Compounds in the Zanthoxylum essential oil were investigated by gas chromatography and mass spectroscopy (GC-MS). The larvicidal bioassays of the whole oil, as well as the main compounds in the oil (estragole and eucalyptol) were performed using WHO method. In total, 63 main compounds (99.32%) were found in the oils, including estragole (15.46%), eucalyptol (10.94%), β-caryophyllene (5.52%), cis-linalool oxide (3.76%), cis-limonene oxide (3.06%). A dose-dependent effect on mortality was recorded with increasing concentrations of essential oil and compounds increasing mortality of the larvae. Larvicidal bioassays revealed that 24 h LC 50 of the whole essential oil was 36.00 mg/L and LC 90 was 101.49 mg/L against An. anthropophagus, while LC 50 was 49.02 mg/L and LC 90 was 125.18 mg/L against An. sinensis. Additionally, 24 h LC 50 of estragole were 38.56 and 41.67 mg/L against An. anthropophagus and An. sinensis, respectively, while the related LC 90 were 95.90 and 107.89 mg/L. LC 50 of eucalyptol were 42.41 and 45.49 mg/L against An. anthropophagus and An. sinensis, while the related LC 90 were 114.45 and 124.95 mg/L. The essential oil of Z. acanthopodium and its several major compounds may have potential for use in the control of malaria mosquitoes.

Genetics of refractoriness to Plasmodium falciparum in the mosquito Anopheles stephensi

NARCIS (Netherlands)

Feldmann, A.M.; Gemert, Geert-Jan van; Vegte-Bolmer, Marga G. van de; Jansen, Ritsert C.

1998-01-01

We previously selected a line of the malaria vector mosquito Anopheles stephensi refractory (resistant) to the human malaria parasite Plasmodium falciparum, using in vitro infections with P. falciparum gametocytes. This report presents data on the genetic background of refractoriness. The results of

»Just cut them up like regular children.« : Eraserhead (USA 1977, David Lynch)

OpenAIRE

Höltgen, Stefan

2010-01-01

Zwischen 1970 und 1977 entsteht in fünfjähriger Dreharbeit mit Unterbrechungen und unter extrem schwierigen Produktionsbedingungen David Lynchs erster Spielfilm "Eraserhead". Vorbereitet wurde er in mehrfacher Hinsicht durch das Frühwerk des noch jungen Regisseurs. Seine kinetische Skulptur "Six Men getting sick", sowie seine Kurzfilme "The Alphabet" und "The Grandmother" verhalfen ihm nicht nur zu Stipendien (etwa der AFI für "The Grandmother"), sondern etablierten auch ein Motivinventar, au...

Screening of selected ethnomedicinal plants from South Africa for larvicidal activity against the mosquito Anopheles arabiensis

CSIR Research Space (South Africa)

Maharaj, R

2012-09-01

Full Text Available through effects of hor- mone regulation with subsequent disruption of instar development of Anopheles stephensi, Culex quinquefas- ciatus and Aedes aegypti [34]. Tiwari et al. [35] found that the essential oil obtained from seeds of Zanthoxy- lum.... Geerts S, Van Blerk K, Triest L: Effect of Ambrosia maritima on Anopheles stephensi and Aedes aegypti. J Ethnopharmacol 1994, 42:7?11. 20. Evans DA, Raj RK: Extracts of Indian plants as mosquito larvicides. Indian J Med Res 1988, 88:38?41. 21...

G protein-coupled receptors in Anopheles gambiae.

Science.gov (United States)

Hill, Catherine A; Fox, A Nicole; Pitts, R Jason; Kent, Lauren B; Tan, Perciliz L; Chrystal, Mathew A; Cravchik, Anibal; Collins, Frank H; Robertson, Hugh M; Zwiebel, Laurence J

2002-10-04

We used bioinformatic approaches to identify a total of 276 G protein-coupled receptors (GPCRs) from the Anopheles gambiae genome. These include GPCRs that are likely to play roles in pathways affecting almost every aspect of the mosquito's life cycle. Seventy-nine candidate odorant receptors were characterized for tissue expression and, along with 76 putative gustatory receptors, for their molecular evolution relative to Drosophila melanogaster. Examples of lineage-specific gene expansions were observed as well as a single instance of unusually high sequence conservation.

The effect of water physical quality and water level changes on the occurrence and density of larvae of Anopheles mosquitoes around the shoreline of the Koka reservoir, Central Ethiopia

Science.gov (United States)

Teklu, B. M.; Tekie, H.; McCartney, M.; Kibret, S.

2010-08-01

Entomological studies to determine the effect of the physical characteristics of larval breeding water bodies and reservoir water level changes on the occurrence of Anopheles mosquito larvae and on the spatial and temporal formation of larval breeding habitats were conducted in two villages at Koka reservoir between August and December 2007. Of the two study villages, Ejersa is in close proximity to the reservoir, and Kuma is 5 km away from it. Data on the type, number and physical characteristics of Anopheles larval breeding habitat, species composition and densities of anopheles mosquitoes in and around the study villages were investigated and recorded. Meteorological and reservoir water level data were compared with availability of Anopheles larval breeding sites and densities. Entomological data from the weekly larval collections showed that Anopheles pharoensis Theobald, Anopheles gambiae s.l. Giles, Anopheles coustani Laveran and Anopheles squamosus Theobald were breeding in the study area. The mean larval density of A. gambiae s.l. in this study was higher in slightly turbid and shallow aquatic habitats than in turbid and relatively deep aquatic habitats (F=16.97, plevels and the number of positive breeding habitats at Ejersa during the sampling period (r=0.605, pphysical characteristics such as water temperature, turbidity, depth and vegetation cover play an important role in the species composition, total Anopheles larval count, and the density of Anopheles mosquitoes in the vicinity. The proliferation of suitable breeding habitats around the reservoir villages is strongly associated with reservoir water level changes. This is particularly important for A. pharoensis and A. arabiensis which are important vectors of malaria in the area. Further investigation on the species diversity, physical and chemical habitat characteristics and impact of water holding capacity of the soil need to be done to generate detailed baseline data which will serve as a basis

Contribution of MLH1 constitutional methylation for Lynch syndrome diagnosis in patients with tumor MLH1 downregulation.

Science.gov (United States)

Pinto, Diana; Pinto, Carla; Guerra, Joana; Pinheiro, Manuela; Santos, Rui; Vedeld, Hege Marie; Yohannes, Zeremariam; Peixoto, Ana; Santos, Catarina; Pinto, Pedro; Lopes, Paula; Lothe, Ragnhild; Lind, Guro Elisabeth; Henrique, Rui; Teixeira, Manuel R

2018-02-01

Constitutional epimutation of the two major mismatch repair genes, MLH1 and MSH2, has been identified as an alternative mechanism that predisposes to the development of Lynch syndrome. In the present work, we aimed to investigate the prevalence of MLH1 constitutional methylation in colorectal cancer (CRC) patients with abnormal expression of the MLH1 protein in their tumors. In a series of 38 patients who met clinical criteria for Lynch syndrome genetic testing, with loss of MLH1 expression in the tumor and with no germline mutations in the MLH1 gene (35/38) or with tumors presenting the BRAF p.Val600Glu mutation (3/38), we screened for constitutional methylation of the MLH1 gene promoter using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in various biological samples. We found four (4/38; 10.5%) patients with constitutional methylation in the MLH1 gene promoter. RNA studies demonstrated decreased MLH1 expression in the cases with constitutional methylation when compared with controls. We could infer the mosaic nature of MLH1 constitutional hypermethylation in tissues originated from different embryonic germ layers, and in one family we could show that it occurred de novo. We conclude that constitutional MLH1 methylation occurs in a significant proportion of patients who have loss of MLH1 protein expression in their tumors and no MLH1 pathogenic germline mutation. Furthermore, we provide evidence that MLH1 constitutional hypermethylation is the molecular mechanism behind about 3% of Lynch syndrome families diagnosed in our institution, especially in patients with early onset or multiple primary tumors without significant family history. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The ecology of Anopheles mosquitoes under climate change: case studies from the effects of deforestation in East African highlands.

Science.gov (United States)

Afrane, Yaw A; Githeko, Andrew K; Yan, Guiyun

2012-02-01

Climate change is expected to lead to latitudinal and altitudinal temperature increases. High-elevation regions such as the highlands of Africa and those that have temperate climate are most likely to be affected. The highlands of Africa generally exhibit low ambient temperatures. This restricts the distribution of Anopheles mosquitoes, the vectors of malaria, filariasis, and O'nyong'nyong fever. The development and survival of larval and adult mosquitoes are temperature dependent, as are mosquito biting frequency and pathogen development rate. Given that various Anopheles species are adapted to different climatic conditions, changes in climate could lead to changes in species composition in an area that may change the dynamics of mosquito-borne disease transmission. It is important to consider the effect of climate change on rainfall, which is critical to the formation and persistence of mosquito breeding sites. In addition, environmental changes such as deforestation could increase local temperatures in the highlands; this could enhance the vectorial capacity of the Anopheles. These experimental data will be invaluable in facilitating the understanding of the impact of climate change on Anopheles. © 2012 New York Academy of Sciences.

A tailored approach to BRAF and MLH1 methylation testing in a universal screening program for Lynch syndrome.

Science.gov (United States)

Adar, Tomer; Rodgers, Linda H; Shannon, Kristen M; Yoshida, Makoto; Ma, Tianle; Mattia, Anthony; Lauwers, Gregory Y; Iafrate, Anthony J; Chung, Daniel C

2017-03-01

To determine the correlation between BRAF genotype and MLH1 promoter methylation in a screening program for Lynch syndrome (LS), a universal screening program for LS was established in two medical centers. Tumors with abnormal MLH1 staining were evaluated for both BRAF V600E genotype and MLH1 promoter methylation. Tumors positive for both were considered sporadic, and genetic testing was recommended for all others. A total 1011 colorectal cancer cases were screened for Lynch syndrome, and 148 (14.6%) exhibited absent MLH1 immunostaining. Both BRAF and MLH1 methylation testing were completed in 126 cases. Concordant results (both positive or both negative) were obtained in 86 (68.3%) and 16 (12.7%) cases, respectively, with 81% concordance overall. The positive and negative predictive values for a BRAF mutation in predicting MLH1 promoter methylation were 98.9% and 41%, respectively, and the negative predictive value fell to 15% in patients ≥70 years old. Using BRAF genotyping as a sole test to evaluate cases with absent MLH1 staining would have increased referral rates for genetic testing by 2.3-fold compared with MLH1 methylation testing alone (31% vs 13.5%, respectively, PMLH1 methylation testing for BRAF wild-type cases only would significantly decrease the number of methylation assays performed and reduce the referral rate for genetic testing to 12.7%. A BRAF mutation has an excellent positive predictive value but poor negative predictive value in predicting MLH1 promoter methylation. A hybrid use of these tests may reduce the number of low-risk patients referred to genetic counseling and facilitate wider implementation of Lynch syndrome screening programs.

PERANAN Anopheles barbirostris VANDER WULP SEBAGAI PENULAR PENYAKIT

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Hasan Boesri

2012-10-01

Full Text Available An. barbirostris is one of mosquito of the genus Anopheles and was classified as 23-57 old days. It can be found at rice fields and swamps at an altitude of 2770 meters above sea level. The most preferred habitat is fresh water and pH 6-7. It is anthropolophilic and endophilic. This species in some areas, especially in East Nusa Tenggara role in transmitting malaria and filariasis.   Key words: An. barbirostris

An Algal Diet Accelerates Larval Growth of Anopheles gambiae (Diptera: Culicidae) and Anopheles arabiensis (Diptera: Culicidae).

Science.gov (United States)

Tuno, N; Kohzu, A; Tayasu, I; Nakayama, T; Githeko, A; Yan, G

2018-01-21

The population sizes of Anopheles gambiae Giles (Diptera: Culicidae) and Anopheles arabiensis Patton (Diptera: Culicidae) increase dramatically with the onset of the rainy season in sub-Saharan Africa, but the ecological mechanisms underlying the increases are not well understood. As a first step toward to understand, we investigated the proliferation of algae, the major food of mosquito larvae, in artificial fresh water bodies exposed to sunlight for a short period, and old water bodies exposed to sunlight for a long period, and the effects thereof on the development of these anopheline larvae. We found that an epizoic green algal species of the genus Rhopalosolen (Chlorophyta: Chlorophyceae) proliferated immediately after water freshly taken from a spring was placed in sunlight. This alga proliferated only briefly (for ~10 d) even if the water was repeatedly exposed to sunlight. However, various algal species were observed in water that remained under sunlight for 40 d or longer (i.e., in old water bodies). The growth performance of larvae was higher in sunlight-exposed (alga-rich) water than in shade-stored (alga-poor) water. Stable isotope analysis suggested that these two anopheline species fed on Rhopalosolen algae in fresh water bodies but hardly at all on other algae occurring in the old water bodies. We concluded that freshly formed ground water pools facilitate high production of anopheline species because of the proliferation of Rhopalosolen algae therein, and the increase in the number of such pools in the rainy season, followed by rapid increases in A. gambiae and A. arabiensis numbers. © The Author(s) 2018. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients

DEFF Research Database (Denmark)

Andersen, Sofie Dabros; Liberti, Sascha Emilie; Lützen, Anne

2012-01-01

Germline mutations in the human DNA mismatch repair (MMR) genes MSH2 and MLH1 are associated with the inherited cancer disorder Lynch Syndrome (LS), also known as Hereditary Nonpolyposis Colorectal Cancer or HNPCC. A proportion of MSH2 and MLH1 mutations found in suspected LS patients give rise...... localization and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer...

STUDI BIOEKOLOGI NYAMUK Anopheles sundaicus DI DESA SUKARESIK KECAMATAN SIDAMULIH KABUPATEN CIAMIS

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Pandji Wibawa Dhewantara

2013-05-01

Full Text Available Abstract Sukaresik village Sidamulih Sub-District Ciamis remains as an area with high risk malaria in West Java. Studying vector bioecology on a region is important to support vector and disease control. A spot-survey study had been conducted during September-November 2011 in order to obtain vector bioecology information in Sukaresik village, Ciamis, i.e breeding sites distribution, vector density, and longevity of Anopheles sundaicus. Potential breeding sites were plotted and its environmental variables, i.e altitude, salinity, water temperature, pH, and water level were measured. Larval collected by dipper and adult mosquitos were captured using human-landing collection which consisted of 12-h (18:00-06:00 indoor and outdoor human-landing captures. Ovary dissection was assigned to female Anopheles sundaicus to measure its longevity. Man-Biting Rate and Man-Hour Density were calculated based on WHO formula. Result shows that there were six potential breeding sites consisted of unproductive fishpool and rice field on 34-46 m asl, salinity 0-0.1‰, water temperature 28-33°C, pH 7, and water level 50-200 cm. A total of 1,012 An. sundaicus were caught during the study. Man-biting rate of An. sundaicus was 1.98 per person per night and its man-hour density was 2.98 per person per hour. Peak landing time of An. sundaicus was between 00.00-04.00; parity rate of dissected 547 female An. sundaicus was 66%; daily survival rate was 0.871; and its longevity was up to 7 days. Keywords: bioecology, vector, malaria, An. sundaicus, Ciamis Abstrak Desa Sukaresik Kecamatan Sidamulih Kabupaten Ciamis masih menjadi salah satu daerah dengan risiko malaria yang cukup tinggi di Jawa Barat. Sebagai bagian dari upaya pengendalian vektor dan  malaria, informasi bioekologi vektor malaria sangat penting untuk dipahami. Sebuah studi dengan desain spot survey telah dilakukan dilakukan di Desa Sukaresik, Kecamatan Sidamulih, Kabupaten Ciamis, Jawa Barat pada bulan

Argyritarsis Section of the Subgenus Nyssorhynchus of Anopheles (Diptera: Culicidae). Revision

Science.gov (United States)

1988-01-01

Nyssorhynchus, corn especial referencia a morfologia dos ovos. Rev. Biol. Hyg. 9:51- 60. 1938b. Observacoes sobre o ciclo evolutivo de Anopheles oswaldoi...Anofelinos do Vale do Paraiba. Nova variedade e ciclo evolutivo do Anofeles (Nyssorhynchus) osvaldoi var. ayrozai n. var. Ann. Paul. Med. Cir. 40:377

Essential Oils as an Alternative to Pyrethroids' Resistance against Anopheles Species Complex Giles (Diptera: Culicidae).

Science.gov (United States)

Gnankiné, Olivier; Bassolé, Imaël Henri Nestor

2017-09-22

Widespread resistance of Anopheles sp. populations to pyrethroid insecticides has led to the search for sustainable alternatives in the plant kingdom. Among many botanicals, there is great interest in essential oils and their constituents. Many researchers have explored essential oils (EOs) to determine their toxicity and identify repellent molecules that are effective against Anopheles populations. Essential oils are volatile and fragrant substances with an oily consistency typically produced by plants. They contain a variety of volatile molecules such as terpenes and terpenoids, phenol-derived aromatic components and aliphatic components at quite different concentrations with a significant insecticide potential, essentially as ovicidal, larvicidal, adulticidal, repellency, antifeedant, growth and reproduction inhibitors. The current review provides a summary of chemical composition of EOs, their toxicity at different developmental stages (eggs, larvae and adults), their repellent effects against Anopheles populations, for which there is little information available until now. An overview of antagonist and synergistic phenomena between secondary metabolites, the mode of action as well as microencapsulation technologies are also given in this review. Finally, the potential use of EOs as an alternative to current insecticides has been discussed.

Locating inputs of freshwater to Lynch Cove, Hood Canal, Washington, using aerial infrared photography

Science.gov (United States)

Sheibley, Rich W.; Josberger, Edward G.; Chickadel, Chris

2010-01-01

The input of freshwater and associated nutrients into Lynch Cove and lower Hood Canal (fig. 1) from sources such as groundwater seeps, small streams, and ephemeral creeks may play a major role in the nutrient loading and hydrodynamics of this low dissolved-oxygen (hypoxic) system. These disbursed sources exhibit a high degree of spatial variability. However, few in-situ measurements of groundwater seepage rates and nutrient concentrations are available and thus may not represent adequately the large spatial variability of groundwater discharge in the area. As a result, our understanding of these processes and their effect on hypoxic conditions in Hood Canal is limited. To determine the spatial variability and relative intensity of these sources, the U.S. Geological Survey Washington Water Science Center collaborated with the University of Washington Applied Physics Laboratory to obtain thermal infrared (TIR) images of the nearshore and intertidal regions of Lynch Cove at or near low tide. In the summer, cool freshwater discharges from seeps and streams, flows across the exposed, sun-warmed beach, and out on the warm surface of the marine water. These temperature differences are readily apparent in aerial thermal infrared imagery that we acquired during the summers of 2008 and 2009. When combined with co-incident video camera images, these temperature differences allow identification of the location, the type, and the relative intensity of the sources.

Evaluation of current prediction models for Lynch syndrome: updating the PREMM5 model to identify PMS2 mutation carriers

NARCIS (Netherlands)

A. Goverde (Anne); M.C.W. Spaander (Manon); D. Nieboer (Daan); A.M.W. van den Ouweland (Ans); W.N.M. Dinjens (Winand); H.J. Dubbink (Erik Jan); C. Tops (Cmj); S.W. Ten Broeke (Sanne W.); M.J. Bruno (Marco); R.M.W. Hofstra (Robert); E.W. Steyerberg (Ewout); A. Wagner (Anja)

2017-01-01

textabstractUntil recently, no prediction models for Lynch syndrome (LS) had been validated for PMS2 mutation carriers. We aimed to evaluate MMRpredict and PREMM5 in a clinical cohort and for PMS2 mutation carriers specifically. In a retrospective, clinic-based cohort we calculated predictions for

Some aspects of molecular diagnostics in Lynch syndrome

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Kurzawski Grzegorz

2006-12-01

Full Text Available Abstract This manuscript is composed of five parts which summarize five publications in succession. Essentially, they are concerned with molecular diagnostics of Lynch syndrome and are based on studies in 238 families. The finding that young age at diagnosis is the key feature in patients with MSH2 and MLH1 mutations (Part 1 has helped to define simple criteria for the preliminary diagnosis of this syndrome. A cheaper method for the detection of mutations has been developed (Part 2 and applied to study the types of mutations and their prevalence in Poland (Part 3 and the Baltic States (Part 4. A specific feature of these mutations, i.e. presence of recurrent mutations in the majority of affected families with mutations, has suggested the feasibility of effective diagnostics with a single test disclosing all of them. An attempt to reveal other causes of familial aggregation of colorectal cancer has ruled out any association with C insertion in the NOD2 gene (Part 5.

Effect of low B-Lynch suture on menstrual cycle recovery and sex hormone levels in patients after cesarean section for placenta previa

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Su-Lan Zhang

2016-03-01

Full Text Available Objective: To explore the effect of low B-Lynch suture on the menstrual cycle recovery and sex hormone levels in patients after cesarean section for placenta previa. Methods: A total of 40 patients who were admitted in our hospital from August, 2013 to August, 2015 for cesarean section due to placenta previa were included in the study and randomized into the observation group and the control group. The patients in the observation group were given low B-lynch suture, while in the control group, yarns were plugged in the uterus. The bleeding during operation and 24 h after operation, the postpartum lochia duration, and menstrual cycle recovery in the two groups were observed. The postpartum FSH, E2, and LH levels in the two groups were determined. Results: The amount of bleeding during operation and 24 h after operation in the observation group was significantly less than that in the control group (P0.05. The comparison of FSH, E2, and LH levels between the two groups was not statistically significant (P>0.05. Conclusions: Low B-Lynch suture can effectively reduce the amount of bleeding after cesarean section for placenta previa, and has no effect on the menstrual recovery and ovarian function with a simple operation and less postoperative complications; therefore, it deserves to be widely recommended in the clinic.

Functional analysis in mouse embryonic stem cells reveals wild-type activity for three MSH6 variants found in suspected Lynch syndrome patients.

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Eva A L Wielders

Full Text Available Lynch syndrome confers an increased risk to various types of cancer, in particular early onset colorectal and endometrial cancer. Mutations in mismatch repair (MMR genes underlie Lynch syndrome, with the majority of mutations found in MLH1 and MSH2. Mutations in MSH6 have also been found but these do not always cause a clear cancer predisposition phenotype and MSH6-defective tumors often do not show the standard characteristics of MMR deficiency, such as microsatellite instability. In particular, the consequences of MSH6 missense mutations are challenging to predict, which further complicates genetic counseling. We have previously developed a method for functional characterization of MSH2 missense mutations of unknown significance. This method is based on endogenous gene modification in mouse embryonic stem cells using oligonucleotide-directed gene targeting, followed by a series of functional assays addressing the MMR functions. Here we have adapted this method for the characterization of MSH6 missense mutations. We recreated three MSH6 variants found in suspected Lynch syndrome families, MSH6-P1087R, MSH6-R1095H and MSH6-L1354Q, and found all three to behave like wild type MSH6. Thus, despite suspicion for pathogenicity from clinical observations, our approach indicates these variants are not disease causing. This has important implications for counseling of mutation carriers.

Diversity and transmission competence in lymphatic filariasis vectors in West Africa, and the implications for accelerated elimination of Anopheles-transmitted filariasis

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de Souza Dziedzom K

2012-11-01

Full Text Available Abstract Lymphatic Filariasis (LF is targeted for elimination by the Global Programme for the Elimination of Lymphatic Filariasis (GPELF. The strategy adopted is based on the density dependent phenomenon of Facilitation, which hypothesizes that in an area where the vector species transmitting Wuchereria bancrofti are Anopheles mosquitoes, it is feasible to eliminate LF using Mass Drug Administration (MDA because of the inability of Anopheles species to transmit low-density microfilaraemia. Even though earlier studies have shown Anopheles species can exhibit the process of Facilitation in West Africa, observations point towards the process of Limitation in certain areas, in which case vector control is recommended. Studies on Anopheles species in West Africa have also shown genetic differentiation, cryptic taxa and speciation, insecticide resistance and the existence of molecular and chromosomal forms, all of which could influence the vectorial capacity of the mosquitoes and ultimately the elimination goal. This paper outlines the uniqueness of LF vectors in West Africa and the challenges it poses to the 2020 elimination goal, based on the current MDA strategies.

Entomologic Inoculation Rates of Anopheles arabiensis in Southwestern Ethiopia

OpenAIRE

Ulesido, Fekadu Massebo; Balkew, Meshesha; Gebre-Michael, Teshome; Lindtjørn, Bernt

2013-01-01

We collected anophelines every second week for one year from randomly selected houses in southwestern Ethiopia by using Centers for Disease Control (CDC) light traps, pyrethrum spray catches, and artificial pit shelter constructions to detect circumsporozoite proteins and estimate entomologic inoculation rates (EIRs). Of 3,678 Anopheles arabiensis tested for circumsporozoite proteins, 11 were positive for Plasmodium falciparum and three for P. vivax. The estimated annual P. falciparum EIR of ...

Factors affecting the vectorial competence of Anopheles gambiae: a question of scale

NARCIS (Netherlands)

Takken, W.; Lindsay, S.W.

2003-01-01

Malaria transmission in Africa is without doubt governed by the existence of a group of highly efficient vectors, of which Anopheles gambiae Giles sensu stricto is predominant. The endophilic and anthropophagic behaviours of this mosquito create an intimate association between the human reservoir

MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer

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Talseth-Palmer Bente A

2010-05-01

Full Text Available Abstract Background Approximately 10% of Lynch syndrome families have a mutation in MSH6 and fewer families have a mutation in PMS2. It is assumed that the cancer incidence is the same in families with mutations in MSH6 as in families with mutations in MLH1/MSH2 but that the disease tends to occur later in life, little is known about families with PMS2 mutations. This study reports on our findings on mutation type, cancer risk and age of diagnosis in MSH6 and PMS2 families. Methods A total of 78 participants (from 29 families with a mutation in MSH6 and 7 participants (from 6 families with a mutation in PMS2 were included in the current study. A database of de-identified patient information was analysed to extract all relevant information such as mutation type, cancer incidence, age of diagnosis and cancer type in this Lynch syndrome cohort. Cumulative lifetime risk was calculated utilising Kaplan-Meier survival analysis. Results MSH6 and PMS2 mutations represent 10.3% and 1.9%, respectively, of the pathogenic mutations in our Australian Lynch syndrome families. We identified 26 different MSH6 and 4 different PMS2 mutations in the 35 families studied. We report 15 novel MSH6 and 1 novel PMS2 mutations. The estimated cumulative risk of CRC at age 70 years was 61% (similar in males and females and 65% for endometrial cancer in MSH6 mutation carriers. The risk of developing CRC is different between males and females at age 50 years, which is 34% for males and 21% for females. Conclusion Novel MSH6 and PMS2 mutations are being reported and submitted to the current databases for identified Lynch syndrome mutations. Our data provides additional information to add to the genotype-phenotype spectrum for both MSH6 and PMS2 mutations.

Screening for germline mutations of MLH1, MSH2, MSH6 and PMS2 genes in Slovenian colorectal cancer patients: implications for a population specific detection strategy of Lynch syndrome.

Science.gov (United States)

Berginc, Gasper; Bracko, Matej; Ravnik-Glavac, Metka; Glavac, Damjan

2009-01-01

Microsatellite instability (MSI) is present in more than 90% of colorectal cancers of patients with Lynch syndrome, and is therefore a feasible marker for the disease. Mutations in MLH1, MSH2, MSH6 and PMS2, which are one of the main causes of deficient mismatch repair and subsequent MSI, have been linked to the disease. In order to establish the role of each of the 4 genes in Slovenian Lynch syndrome patients, we performed MSI analysis on 593 unselected CRC patients and subsequently searched for the presence of point mutations, larger genomic rearrangements and MLH1 promoter hypermethylation in patients with MSI-high tumours. We detected 43 (7.3%) patients with MSI-H tumours, of which 7 patients (1.3%) harboured germline defects: 2 in MLH1, 4 in MSH2, 1 in PMS2 and none in MSH6. Twenty-nine germline sequence variations of unknown significance and 17 deleterious somatic mutations were found. MLH1 promoter methylation was detected in 56% of patients without detected germline defects and in 1 (14%) suspected Lynch syndrome. Due to the minor role of germline MSH6 mutations, we adapted the Lynch syndrome detection strategy for the Slovenian population of CRC patients, whereby germline alterations should be first sought in MLH1 and MSH2 followed by a search for larger genomic rearrangements in these two genes. When no germline mutations are found tumors should be further tested for the presence of germline defects in PMS2 and MSH6. The choice about which gene should be tested first can be guided more accurately by the immunohistochemical analysis. Our study demonstrates that the incidence of MMR mutations in a population should be known prior to the application of one of several suggested strategies for detection of Lynch syndrome.

Additional selection for insecticide resistance in urban malaria vectors: DDT resistance in Anopheles arabiensis from Bobo-Dioulasso, Burkina Faso.

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Christopher M Jones

Full Text Available In the city of Bobo-Dioulasso in Burkina Faso, Anopheles arabiensis has superseded Anopheles gambiae s.s. as the major malaria vector and the larvae are found in highly polluted habitats normally considered unsuitable for Anopheles mosquitoes. Here we show that An. gambiae s.l. adults emerging from a highly polluted site in the city centre (Dioulassoba have a high prevalence of DDT resistance (percentage mortality after exposure to diagnostic dose=65.8% in the dry season and 70.4% in the rainy season, respectively. An investigation into the mechanisms responsible found an unexpectedly high frequency of the 1014S kdr mutation (allele frequency=0.4, which is found at very low frequencies in An. arabiensis in the surrounding rural areas, and an increase in transcript levels of several detoxification genes, notably from the glutathione transferase and cytochrome P450 gene families. A number of ABC transporter genes were also expressed at elevated levels in the DDT resistant An. arabiensis. Unplanned urbanisation provides numerous breeding grounds for mosquitoes. The finding that Anopheles mosquitoes adapted to these urban breeding sites have a high prevalence of insecticide resistance has important implications for our understanding of the selective forces responsible for the rapid spread of insecticide resistant populations of malaria vectors in Africa.

Inference of the oxidative stress network in Anopheles stephensi upon Plasmodium infection.

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Shrinet, Jatin; Nandal, Umesh Kumar; Adak, Tridibes; Bhatnagar, Raj K; Sunil, Sujatha

2014-01-01

Ookinete invasion of Anopheles midgut is a critical step for malaria transmission; the parasite numbers drop drastically and practically reach a minimum during the parasite's whole life cycle. At this stage, the parasite as well as the vector undergoes immense oxidative stress. Thereafter, the vector undergoes oxidative stress at different time points as the parasite invades its tissues during the parasite development. The present study was undertaken to reconstruct the network of differentially expressed genes involved in oxidative stress in Anopheles stephensi during Plasmodium development and maturation in the midgut. Using high throughput next generation sequencing methods, we generated the transcriptome of the An. stephensi midgut during Plasmodium vinckei petteri oocyst invasion of the midgut epithelium. Further, we utilized large datasets available on public domain on Anopheles during Plasmodium ookinete invasion and Drosophila datasets and arrived upon clusters of genes that may play a role in oxidative stress. Finally, we used support vector machines for the functional prediction of the un-annotated genes of An. stephensi. Integrating the results from all the different data analyses, we identified a total of 516 genes that were involved in oxidative stress in An. stephensi during Plasmodium development. The significantly regulated genes were further extracted from this gene cluster and used to infer an oxidative stress network of An. stephensi. Using system biology approaches, we have been able to ascertain the role of several putative genes in An. stephensi with respect to oxidative stress. Further experimental validations of these genes are underway.

Smoking and colorectal cancer in Lynch syndrome: Results from the Colon Cancer Family Registry and The University of Texas M. D. Anderson Cancer Center

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Pande, Mala; Lynch, Patrick M.; Hopper, John L.; Jenkins, Mark A.; Gallinger, Steve; Haile, Robert W.; LeMarchand, Loic; Lindor, Noralane M.; Campbell, Peter T.; Newcomb, Polly A.; Potter, John D.; Baron, John A.; Frazier, Marsha L.; Amos, Christopher I.

2009-01-01

Purpose Lynch syndrome family members with inherited germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC) and cases typically have tumors that exhibit a high level of microsatellite instability (MSI). There is some evidence that smoking is a risk factor for CRCs with high MSI, but the association of smoking with CRC among those with Lynch syndrome is unknown. Experimental Design A multicentered retrospective cohort of 752 carriers of pathogenic MMR gene mutations was analyzed, using a weighted Cox regression analysis, adjusting for sex, ascertainment source, the specific mutated gene, year of birth, and familial clustering. Results Compared with never smokers, current smokers had a significantly increased CRC risk (adjusted hazard ratio [HR] = 1.62; 95% CI, 1.01 – 2.57) and former smokers who had quit smoking for 2 or more years were at decreased risk (HR = 0.53; 95% CI, 0.35 – 0.82). CRC risk did not vary according to age at starting. However, light smoking (Lynch syndrome may be at increased risk of CRC if they smoke regularly. Although our data suggest that former smokers, short-term and light smokers are at decreased CRC risk, these findings need further confirmation, preferably using prospective designs. PMID:20145170

El doctor Moreno Pérez y el anopheles crucians

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Facultad de Medicina Revista

1943-03-01

Full Text Available En el año de 1933, con ocasión del conflicto del Amazonas, el doctor Ignacio Moreno·Pérez trabajó como médico de sanidad en la hoya del río Caquetá. Prosiguiendo sus estudios sobre paludismo y mosquitos transmisores a que dedicó gran parte de su meritoria vida, practicó una inspección entomológica de las cercanías de Florencia, capital de la comisaria del Caquetá, y encontró una raza en aguas salobres de Anopheles crucians. El hallazgo comunicado por él en el informe de 1934 de la comisión de paludismo del valle del Magdalena, (Estudios de Paludismo en el Valle del Magdalena, Departamento Nacional de Higiene, Sección de Sanidad Rural, Bogotá editorial de "Cromos", 1934, despertó mucho interés y fué objeto de controversias, porque conforme a los estudios de Howard, Dyar y Knab (1917, la localización del Anopheles crucians era casi hiperbórea, por encima del paralelo 25 en la América del Norte y solamente se había logrado ver además en Cuba y Jamaica.

Inference of the oxidative stress network in Anopheles stephensi upon Plasmodium infection

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Shrinet, Jatin; Nandal, Umesh Kumar; Adak, Tridibes; Bhatnagar, Raj K.; Sunil, Sujatha

2014-01-01

Ookinete invasion of Anopheles midgut is a critical step for malaria transmission; the parasite numbers drop drastically and practically reach a minimum during the parasite's whole life cycle. At this stage, the parasite as well as the vector undergoes immense oxidative stress. Thereafter, the

Avoidance behavior to essential oils by Anopheles minimus, a malaria vector in Thailand

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Excito-repellency tests were used to characterize behavioral responses of laboratory colonized Anopheles minimus, a malaria vector in Thailand, using four essential oils, citronella (Cymbopogom nadus), hairy basil (Ocimum americanum), sweet basil (Ocimum basilicum), vetiver (Vetiveria zizanioides), ...

Genetic evidence for malaria vectors of the Anopheles sundaicus complex in Sri Lanka with morphological characteristics attributed to Anopheles subpictus species B

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Jude Pavillupillai J

2010-11-01

Full Text Available Abstract Background Anopheles subpictus sensu lato, a widespread malaria vector in Asia, is reportedly composed of four sibling species A - D. Mosquitoes morphologically identified as belonging to the Subpictus complex were collected from different locations near the east coast of Sri Lanka, and specific ribosomal DNA sequences determined to validate their taxonomic status. Methods Anopheles subpictus s.l. larvae and blood-fed adults were collected from different locations in the Eastern province and their sibling species status was determined based on published morphological characteristics. DNA sequences of the D3 domain of 28 S ribosomal DNA (rDNA and the internal transcribed spacer -2 (ITS-2 of mosquitoes morphologically identified as An. subpictus sibling species A, B, C and D were determined. Results Phylogenetic analysis based on D3 domain of rDNA resulted in two clades: one clade with mosquitoes identified as An. subpictus species A, C, D and some mosquitoes identified as species B, and another clade with a majority of mosquitoes identified as species B with D3 sequences that were identical to Anopheles sundaicus cytotype D. Analysis of ITS-2 sequences confirmed a close relationship between a majority of mosquitoes identified as An. subpictus B with members of the An. sundaicus complex and others identified as An. subpictus B with An. subpictus s.l. Conclusions The study suggests that published morphological characteristics are not specific enough to identify some members of the Subpictus complex, particularly species B. The sequences of the ITS-2 and D3 domain of rDNA suggest that a majority that were identified morphologically as An. subpictus species B in the east coast of Sri Lanka, and some identified elsewhere in SE Asia as An. subpictus s.l., are in fact members of the Sundaicus complex based on genetic similarity to An. sundaicus s.l. In view of the well-known ability of An. sundaicus s.l. to breed in brackish and fresh water and

Dietary patterns and colorectal adenomas in Lynch syndrome: the GEOLynch cohort study.

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Botma, Akke; Vasen, Hans F A; van Duijnhoven, Fränzel J B; Kleibeuker, Jan H; Nagengast, Fokko M; Kampman, Ellen

2013-02-01

Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in LS patients was assessed. In the GEOLynch cohort of 486 persons with LS, dietary information was collected, using a food frequency questionnaire. Dietary pattern scores were obtained by principal components analysis. Hazard ratios (HR) between dietary patterns and colorectal adenomas were calculated using Cox regression models. Robust sandwich variance estimates were used to control for dependency within families. Final models were adjusted for age, sex, smoking habits, colorectal adenoma history, and extent of colon resection. During a median follow-up of 20 months, colorectal adenomas were detected in 58 persons. Four dietary patterns were identified: a "Prudent," "Meat," "Snack," and "Cosmopolitan" pattern. Individuals within the highest tertile of the "Prudent" pattern had a HR of 0.73 (95% confidence interval [CI], 0.32-1.66) for colorectal adenomas, compared with the lowest tertile. Those with high "Meat" pattern scores had a HR of 1.70 (95% CI, 0.83-3.52). A high "Snack" pattern was associated with an increased risk of colorectal adenomas (HR, 2.16; 95% CI, 1.03-4.49). A HR of 1.25 (95% CI, 0.61-2.55) was observed for persons in the highest tertile of the "Cosmopolitan" pattern. These findings suggest that dietary patterns may be associated with development of colorectal adenoma in patients with Lynch syndrome. The directions of these findings are corroborative with those observed in studies investigating sporadic colorectal cancer. Copyright © 2012 American Cancer Society.

Bionomics of Anopheles fluviatilis and Anopheles culicifacies (Diptera: Culicidae) in Relation to Malaria Transmission in East-Central India.

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Sahu, S S; Gunasekaran, K; Krishnamoorthy, N; Vanamail, P; Mathivanan, A; Manonmani, A; Jambulingam, P

2017-07-01

The southern districts of Odisha State in east-central India have been highly endemic for falciparum malaria for many decades. However, there is no adequate information on the abundance of the vector species or their bionomics in relation to space and time in these districts. Therefore, a study was carried out on the entomological aspects of malaria transmission to generate such information. Collections of mosquitoes were made once during each of the three seasons in 128 villages selected from eight districts. Villages within the foot-hill ecotype had a significantly greater abundance of Anopheles fluviatilis James s. l., whereas the abundance of Anopheles culicifacies Giles s. l. was significantly greater in the plain ecotype. The abundance of An. fluviatilis was maximum during the cold season, whereas An. culicifacies abundance was highest during summer and rainy seasons. The maximum likelihood estimation of the malaria infection rate in An. fluviatilis was 1.78%, 6.05%, and 2.6% in Ganjam, Kalahandi, and Rayagada districts, respectively. The infection rate of An. culicifacies was 1.39% only in Kandhamal district; infected females were not detected elsewhere. Concurrently, the annual malaria parasite incidence (MPI) was significantly higher in hill-top (17.6) and foot-hill (14.4) villages compared to plain villages (4.1). The districts with more villages in hill-top and foot-hill ecotypes also had a greater abundance of An. fluviatilis, the major malaria vector, and exhibited a higher incidence of malaria than villages within the plain ecotype, where An. culicifacies was the most abundant vector. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

Thermal behaviour of Anopheles stephensi in response to infection with malaria and fungal entomopathogens

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Read Andrew F

2009-04-01

Full Text Available Abstract Background Temperature is a critical determinant of the development of malaria parasites in mosquitoes, and hence the geographic distribution of malaria risk, but little is known about the thermal preferences of Anopheles. A number of other insects modify their thermal behaviour in response to infection. These alterations can be beneficial for the insect or for the infectious agent. Given current interest in developing fungal biopesticides for control of mosquitoes, Anopheles stephensi were examined to test whether mosquitoes showed thermally-mediated behaviour in response to infection with fungal entomopathogens and the rodent malaria, Plasmodium yoelii. Methods Over two experiments, groups of An. stephensi were infected with one of three entomopathogenic fungi, and/or P. yoelii. Infected and uninfected mosquitoes were released on to a thermal gradient (14 – 38°C for "snapshot" assessments of thermal preference during the first five days post-infection. Mosquito survival was monitored for eight days and, where appropriate, oocyst prevalence and intensity was assessed. Results and conclusion Both infected and uninfected An. stephensi showed a non-random distribution on the gradient, indicating some capacity to behaviourally thermoregulate. However, chosen resting temperatures were not altered by any of the infections. There is thus no evidence that thermally-mediated behaviours play a role in determining malaria prevalence or that they will influence the performance of fungal biopesticides against adult Anopheles.

Clinicopathological Features and Management of Cancers in Lynch Syndrome

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Markku Aarnio

2012-01-01

Full Text Available Lynch syndrome (LS is characterized by an autosomal dominant inheritance of the early onset of colorectal cancer (CRC and endometrial cancer, as well as increased risk for several other cancers including gastric, urinary tract, ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR genes MLH1, MSH2, MSH6, or PMS2. The majority of LS patients and families can now be identified, and the underlying mutation detected using genetic diagnostics. Regular surveillance for CRC and endometrial cancer has proved beneficial for mutation carriers. However, screening for other tumors is also recommended even though experiences in the screening of these tumors is limited. Prophylactic colectomy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for selected patients with LS. This paper describes the features and management of LS.

Insertion of an SVA element, a nonautonomous retrotransposon, in PMS2 intron 7 as a novel cause of Lynch syndrome.

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van der Klift, Heleen M; Tops, Carli M; Hes, Frederik J; Devilee, Peter; Wijnen, Juul T

2012-07-01

Heterozygous germline mutations in the mismatch repair gene PMS2 predispose carriers for Lynch syndrome, an autosomal dominant predisposition to cancer. Here, we present a LINE-1-mediated retrotranspositional insertion in PMS2 as a novel mutation type for Lynch syndrome. This insertion, detected with Southern blot analysis in the genomic DNA of the patient, is characterized as a 2.2 kb long 5' truncated SVA_F element. The insertion is not detectable by current diagnostic testing limited to MLPA and direct Sanger sequencing on genomic DNA. The molecular nature of this insertion could only be resolved in RNA from cultured lymphocytes in which nonsense-mediated RNA decay was inhibited. Our report illustrates the technical problems encountered in the detection of this mutation type. Especially large heterozygous insertions will remain unnoticed because of preferential amplification of the smaller wild-type allele in genomic DNA, and are probably underreported in the mutation spectra of autosomal dominant disorders. © 2012 Wiley Periodicals, Inc.

Irritant and repellent responses of Anopheles harrisoni and Anopheles minimus upon exposure to bifenthrin or deltamethrin using an excito-repellency system and a live host.

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Kongmee, Monthathip; Boonyuan, Wasana; Achee, Nicole L; Prabaripai, Atchariya; Lerdthusnee, Kriangkrai; Chareonviriyaphap, Theeraphap

2012-03-01

Feeding responses of Anopheles harrisoni and An. minimus were evaluated following exposure to 2 pyrethroid insecticides, bifenthrin or deltamethrin, using an excito-repellency test system in the presence and absence of live host cues. The results demonstrated that contact irritancy was the primary action of bifenthrin or deltamethrin in both mosquito species. There was no noncontact repellency effect elicited by either insecticide. Anopheles minimus showed rapid escape response with high mortality rates following direct contact with deltamethrin in the absence of a host and delayed escape responses when a host was present. Similarly, exposure of An. minimus to bifenthrin also elicited a delayed escape response in the presence of a host but with lower mortality rates. In experiments using An. harrisoni, the presence or absence of a host had no significant effect on behavioral responses to either insecticide (P > 0.05). We conclude that deltamethrin elicited stronger irritant chemical effects than bifenthrin but that behavioral responses in vector populations are dampened in the presence of an available host. This information is useful for estimating probability of pathogen transmission when using irritant chemicals in proximity to a blood-meal source.

Satellite-derived NDVI, LST, and climatic factors driving the distribution and abundance of Anopheles mosquitoes in a former malarious area in northwest Argentina.

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Dantur Juri, María Julia; Estallo, Elizabet; Almirón, Walter; Santana, Mirta; Sartor, Paolo; Lamfri, Mario; Zaidenberg, Mario

2015-06-01

Distribution and abundance of disease vectors are directly related to climatic conditions and environmental changes. Remote sensing data have been used for monitoring environmental conditions influencing spatial patterns of vector-borne diseases. The aim of this study was to analyze the effect of the Normalized Difference Vegetation Index (NDVI) and Land Surface Temperature (LST) obtained from the Moderate Resolution Imaging Spectroradiometer (MODIS), and climatic factors (temperature, humidity, wind velocity, and accumulated rainfall) on the distribution and abundance of Anopheles species in northwestern Argentina using Poisson regression analyses. Samples were collected from December, 2001 to December, 2005 at three localities, Aguas Blancas, El Oculto and San Ramón de la Nueva Orán. We collected 11,206 adult Anopheles species, with the major abundance observed at El Oculto (59.11%), followed by Aguas Blancas (22.10%) and San Ramón de la Nueva Orán (18.79%). Anopheles pseudopunctipennis was the most abundant species at El Oculto, Anopheles argyritarsis predominated in Aguas Blancas, and Anopheles strodei in San Ramón de la Nueva Orán. Samples were collected throughout the sampling period, with the highest peaks during the spring seasons. LST and mean temperature appear to be the most important variables determining the distribution patterns and major abundance of An. pseudopunctipennis and An. argyritarsis within malarious areas. © 2015 The Society for Vector Ecology.

Field evaluation of synthetic lure (3-methyl-1-butanol) when compared to non odor-baited control in capturing Anopheles mosquitoes in varying land-use sites in Madagascar.

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Zohdy, Sarah; Derfus, Kristin; Andrianjafy, Mbolatiana Tovo; Wright, Patricia C; Gillespie, Thomas R

2015-03-07

Malaria is the 4(th) largest cause of mortality in Madagascar. To better understand malaria transmission dynamics, it is crucial to map the distribution of the malaria vectors, mosquitoes belonging to the genus Anopheles. To do so, it is important to have a strong Anopheles-specific lure to ensure the maximum number of captures. Previous studies have isolated volatiles from the human skin microbiota and found the compound 3-methyl-1-butanol to be the most attractive to the malaria mosquito, Anopheles gambiae, in a laboratory setting; and recommended 3-methyl-1-butanol as a compound to increase An. gambiae captures in the field. To date, this compound's ability to lure wild mosquitoes in differing land-use settings has not been tested. In this study, we evaluate the role of the synthetic compound, 3-methyl-1-butanol in combination with field produced CO(2) in attracting Anopheles mosquitoes in varying land-use sites in Madagascar. CDC miniature light traps in combination with field produced CO(2) were deployed in and around six villages near Ranomafana National Park, Madagascar. To test the role of 3-methyl-1-butanol in luring Anopheles mosquitoes, two traps were set in each land-use site (village, agricultural sites, and forested habitats affiliated with each village). One was baited with the synthetic odor and the other was kept as a non-baited control. While 3-methyl-1-butanol baited traps did capture An. gambiae s.l. in this study, we did not find traps baited with synthetic 3-methyl-1-butanol to be more successful in capturing Anopheles mosquitoes, (including Anopheles gambiae s.l.) than the non odor-baited control traps in any of the land-use sites examined; however, regardless of odor bait, trapping near livestock pens resulted in the capture of significantly more Anopheles specimens. A strong synthetic lure in combination with insecticide has great potential as a mosquito control. Our findings suggest that trapping mosquitoes near livestock in malaria

Aspectos ecológicos de Anopheles cruzii e Culex ribeirensis (Diptera, Culicidae da Mata Atlântica de Morretes, Paraná, Brasil Ecological aspects of Anopheles cruzii and Culex ribeirensis (Diptera, Culicidae in Atlantic Forest of Morretes, Paraná, Brazil

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Luiz Gonzaga dos Santos-Neto

2008-01-01

Full Text Available Um estudo foi realizado sobre mosquitos adultos de abril 1995 a março 1996 na Mata Atlântica do município de Morretes, Paraná, Brasil. A investigação foi procedida com auxílio de duas armadilhas luminosas CDC-M instaladas em estratos verticais diferentes. Os mosquitos foram capturados mensalmente durante um ano, com início às 18 horas e término às 6 horas do dia seguinte, totalizando 144 horas de trabalho de campo. Obteve-se 1.408 exemplares de mosquitos (409 na copa e 999 próximo ao solo, pertencentes a 10 gêneros e 31 espécies. Anopheles cruzii e Culex ribeirensis foram predominantes e são objetos do presente estudo. Não foi observada diferença entre as armadilhas para Anopheles cruzii. Mas Culex ribeirensis foi coletado em maior número pela CDC-M/solo. Anopheles cruzii, quanto à freqüência horária, apresentou picos nas primeiras horas da noite, depois a sua atividade decresceu progressivamente até o crepúsculo matutino, sem apresentar um pico secundário. Em referência a distribuição mensal, Anopheles cruzii foi mais freqüente nos meses de abril e maio de 1995 e março de 1996. Não houve correlação do número de exemplares com a temperatura ou precipitações pluviométricas. Culex ribeirensis apresentou maior atividade de vôo de 22h às 4h, mas não houve picos significativos. Nas coletas obtidas por mês, Culex ribeirensis teve picos em dezembro e janeiro. Houve correlação do número de espécimes deste culicíneo com a temperatura e precipitações pluviométricas. Constituem os primeiros registros para o Estado do Paraná: Ochlerotatus rhyacophilus, Culex misionensis, Culex pedroi, Culex ribeirensis e Culex zeteki.A study of adult mosquitoes was performed from April 1995 to March 1996 in the Atlantic Forest near to Morretes city, Paraná, Brazil. The research was carried out by using two CDC-M light traps installed in different vertical stratification levels. Mosquitoes were collected monthly throughout

Characterizing the insecticide resistance of Anopheles gambiae in Mali.

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Cisse, Moussa B M; Keita, Chitan; Dicko, Abdourhamane; Dengela, Dereje; Coleman, Jane; Lucas, Bradford; Mihigo, Jules; Sadou, Aboubacar; Belemvire, Allison; George, Kristen; Fornadel, Christen; Beach, Raymond

2015-08-22

The impact of indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs), key components of the national malaria control strategy of Mali, is threatened by vector insecticide resistance. The objective of this study was to assess the level of insecticide resistance in Anopheles gambiae sensu lato populations from Mali against four classes of insecticide recommended for IRS: organochlorines (OCs), pyrethroids (PYs), carbamates (CAs) and organophosphates (OPs). Characterization of resistance was done in 13 sites across southern Mali and assessed presence and distribution of physiological mechanisms that included target-site modifications: knockdown resistance (kdr) and altered acetycholinesterase (AChE), and/or metabolic mechanisms: elevated esterases, glutathione S-transferases (GSTs), and monooxygenases. The World Health Organization (WHO) tube test was used to determine phenotypic resistance of An. gambiae s.l. to: dichlorodiphenyltrichloroethane (DDT) (OC), deltamethrin (PY), lambda-cyhalothrin (PY), bendiocarb (CA), and fenitrothion (OP). Identification of sibling species and presence of the ace-1 (R) and Leu-Phe kdr, resistance-associated mutations, were determined using polymerase chain reaction (PCR) technology. Biochemical assays were conducted to detect increased activity of GSTs, oxidases and esterases. Populations tested showed high levels of resistance to DDT in all 13 sites, as well as increased resistance to deltamethrin and lambda-cyhalothrin in 12 out of 13 sites. Resistance to fenitrothion and bendiocarb was detected in 1 and 4 out of 13 sites, respectively. Anopheles coluzzii, An. gambiae sensu stricto and Anopheles arabiensis were identified with high allelic frequencies of kdr in all sites where each of the species were found (13, 12 and 10 sites, respectively). Relatively low allelic frequencies of ace-1 (R) were detected in four sites where this assessment was conducted. Evidence of elevated insecticide metabolism, based on oxidase

Effect of Bacillus sphaericus Neide on Anopheles (Diptera: Culicidae and associated insect fauna in fish ponds in the Amazon

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Francisco Augusto da Silva Ferreira

2015-09-01

Full Text Available ABSTRACTWe analyzed the effects of Bacillus sphaericus on Anopheles larvae and on the associated insect fauna in fish farming ponds. Five breeding sites in the peri-urban area of the city of Manaus, AM, Brazil, were studied. Seven samples were collected from each breeding site and B. sphaericus was applied and reapplied after 15 days. The samples were made at 24 h before application, 24 h post-application and 5 and 15 days post-application. We determined abundance, larval reduction and larval density for Anopheles, and abundance, richness, Shannon diversity index and classified according to the functional trophic groups for associated insect fauna. A total of 904 Anopheles larvae were collected and distributed into five species. Density data and larval reduction demonstrated the rapid effect of the biolarvicide 24 h after application. A total of 4874 associated aquatic insects belonging to six orders and 23 families were collected. Regression analysis of diversity and richness indicated that the application of the biolarvicide had no influence on these indices and thus no effect on the associated insect fauna for a period of 30 days. B. sphaericus was found to be highly effective against the larvae of Anopheles, eliminating the larvae in the first days after application, with no effect on the associated insect fauna present in the fish ponds analyzed.

La mujer en el radiador en Cabeza borradora (Eraserhead, 1972-1976) de David Lynch: disección utópica del ojo

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Villaplana Ruiz, Virginia

1998-01-01

Villaplana, V. (1998). La mujer en el radiador en Cabeza borradora (Eraserhead, 1972-1976) de David Lynch: disección utópica del ojo. Banda aparte. (11):29-31. http://hdl.handle.net/10251/43165. 29 31 11

The susceptibility of Anopheles lesteri to infection with Korean strain of Plasmodium vivax

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Kim Tong-Soo

2009-03-01

Full Text Available Abstract Background Following its recent re-emergence, malaria has gained renewed attention as a serious infectious disease in Korea. Three species of the Hyrcanusgroup, Anopheles lesteri, Anopheles sinensis and Anopheles pullus, have long been suspected malaria vectors. However, opinions about their vector ability are controversial. The present study was designed with the aim of determining the susceptibility of these mosquitoes to a Korean isolate of Plasmodium vivax. Also, An. sinensis is primarily suspected to be vector of malaria in Korea, but in Thailand, the same species is described to have less medical importance. Therefore, comparative susceptibility of Thai and Korean strains of An. sinensis with Thai strain of P. vivax may be helpful to understand whether these geographically different strains exhibit differences in their susceptibility or not. Methods The comparative susceptibility of An. lesteri, An. sinensis and An. pullus was studied by feeding laboratory-reared mosquitoes on blood from patients carrying gametocytes from Korea and Thailand. Results In experimental feeding with Korean strain of P. vivax, oocysts developed in An. lesteri, An. sinensis and An. pullus. Salivary gland sporozoites were detected only in An. lesteri and An. sinensis but not in An. pullus. Large differences were found in the number of sporozoites in the salivary glands, with An. lesteri carrying much higher densities, up to 2,105 sporozoites in a single microscope field of 750 × 560 μM, whereas a maximum of 14 sporozoites were found in any individual salivary gland of An. sinensis. Similar results were obtained from a susceptibility test of two different strains of An. sinensis to Thai isolate of P. vivax, and differences in vector susceptibility according to geographical variation were not detected. Conclusion The high sporozoite rate and sporozoite loads of An. lesteri indicate that this species is highly susceptible to infection with P. vivax

Retrospective study of malaria prevalence and Anopheles genus in the area of influence of the binational Itaipu reservoir Estudo retrospectivo da prevalência de malária e do gênero Anopheles na área de influência do reservatório de Itaipu Binacional

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Ana Lucia Falavigna-Guilherme

2005-04-01

Full Text Available The importance of hydroelectric dams beside the human interchange in the maintenance of malarious foci and the occurrence of the Anopheles genus on the Binational Itaipu Reservoir were the main points of this retrospective study. Data were collected from existing registrations at National, State and Municipal Health Departments and literature systematic overview, from January 1984 to December 2003. The occurrence of some outbreak of malaria, mainly by Plasmodium vivax, and the prevalence of species of the Anopheles genus different from Anopheles darlingi in the region are discussed. The malaria in the left bank of Paraná River is a focal problem, which must be approached locally through health, educational and social actions to prevent the continuity of outbreaks in the area. Concomitantly, it is necessary to plan and apply effective surveillance measures in the influence area of the Itaipu Reservoir.A importância de reservatórios de hidroelétricas e do intercâmbio humano na manutenção de focos de malária e a ocorrência do gênero Anopheles no reservatório de Itaipu Binacional foram os pontos destacados neste estudo retrospectivo. Os dados foram coletados de registros existentes em órgãos municipais, estadual e nacional de saúde e por revisão sistemática da literatura, no período de janeiro de 1984 a dezembro de 2003. A ocorrência de alguns surtos de malária, principalmente por Plasmodium vivax, e a prevalência de espécies do gênero Anopheles diferentes de Anopheles darlingi na região foram discutidos. A malária na margem esquerda do rio Paraná é um problema focal que deve ser abordado localmente através de medidas voltadas à saúde, educação e área social que previnam a continuidade da ocorrência de surtos na área. Concomitantemente, é necessário planejar e aplicar medidas efetivas de vigilância epidemiológica na área de influência do reservatório de Itaipu.

Ecology of Anopheles darlingi Root with respect to vector importance: a review

NARCIS (Netherlands)

Hiwat, H.; Bretas, G.

2011-01-01

Anopheles darlingi is one of the most important malaria vectors in the Americas. In this era of new tools and strategies for malaria and vector control it is essential to have knowledge on the ecology and behavior of vectors in order to evaluate appropriateness and impact of control measures. This

Food of larval Anopheles culicifacies and Anopheles varuna in a stream habitat in Sri Lanka

DEFF Research Database (Denmark)

Piyaratne, M K; Amerasinghe, P H; Amerasinghe, F P

2005-01-01

-phenylindole, was used to stain larval gut contents. Quantitative estimates of different categories of food types were made by analyzing the gut contents of 95 An. culicifacies (26 second instars and 69 fourth instars) and 52 An. varuna (21 second instars and 31 fourth instars). Detritus was the most frequent......No previous studies have been conducted on the natural food of larval Anopheles culicifacies s.l. (the major malaria vector) and An. varuna (a secondary vector) in Sri Lanka. The present study analyzed the contents of guts dissected from larvae collected from pools in a natural stream...... food type, comprising >74% of the gut contents in both species. Other food types included bacteria (cocci and rods), filamentous algae, diatoms, and desmids. Overall, bacteria constituted a significantly higher proportion of the gut contents in An. culicifacies than in An varuna. Significantly more...

Rapid evolution of female-biased genes among four species of Anopheles malaria mosquitoes.

Science.gov (United States)

Papa, Francesco; Windbichler, Nikolai; Waterhouse, Robert M; Cagnetti, Alessia; D'Amato, Rocco; Persampieri, Tania; Lawniczak, Mara K N; Nolan, Tony; Papathanos, Philippos Aris

2017-09-01

Understanding how phenotypic differences between males and females arise from the sex-biased expression of nearly identical genomes can reveal important insights into the biology and evolution of a species. Among Anopheles mosquito species, these phenotypic differences include vectorial capacity, as it is only females that blood feed and thus transmit human malaria. Here, we use RNA-seq data from multiple tissues of four vector species spanning the Anopheles phylogeny to explore the genomic and evolutionary properties of sex-biased genes. We find that, in these mosquitoes, in contrast to what has been found in many other organisms, female-biased genes are more rapidly evolving in sequence, expression, and genic turnover than male-biased genes. Our results suggest that this atypical pattern may be due to the combination of sex-specific life history challenges encountered by females, such as blood feeding. Furthermore, female propensity to mate only once in nature in male swarms likely diminishes sexual selection of post-reproductive traits related to sperm competition among males. We also develop a comparative framework to systematically explore tissue- and sex-specific splicing to document its conservation throughout the genus and identify a set of candidate genes for future functional analyses of sex-specific isoform usage. Finally, our data reveal that the deficit of male-biased genes on the X Chromosomes in Anopheles is a conserved feature in this genus and can be directly attributed to chromosome-wide transcriptional regulation that de-masculinizes the X in male reproductive tissues. © 2017 Papa et al.; Published by Cold Spring Harbor Laboratory Press.

Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency Syndrome

NARCIS (Netherlands)

Klift, H.M. van der; Mensenkamp, A.R.; Drost, M.; Bik, E.C.; Vos, Y.J.; Gille, H.J.; Redeker, B.E.; Tiersma, Y.; Zonneveld, J.B.; Garcia, E.G.; Letteboer, T.G.; Olderode-Berends, M.J.; Hest, L.P. van; Os, T.A. van; Verhoef, S.; Wagner, A.; Asperen, C.J. van; Broeke, S.W. ten; Hes, F.J.; Wind, N. de; Nielsen, M.; Devilee, P.; Ligtenberg, M.J.L.; Wijnen, J.T.; Tops, C.M.

2016-01-01

Monoallelic PMS2 germline mutations cause 5%-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA- and RNA-based strategies are

Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency Syndrome

NARCIS (Netherlands)

van der Klift, Heleen M.; Mensenkamp, Arjen R.; Drost, Mark; Bik, Elsa C.; Vos, Yvonne J.; Gille, Hans J. J. P.; Redeker, Bert E. J. W.; Tiersma, Yvonne; Zonneveld, Jose B. M.; Garcia, Encarna Gomez; Letteboer, Tom G. W.; Olderode-Berends, Maran J. W.; van Hest, Liselotte P.; van Os, Theo A.; Verhoef, Senno; Wagner, Anja; van Asperen, Christi J.; ten Broeke, Sanne W.; Hes, Frederik J.; de Wind, Niels; Nielsen, Maartje; Devilee, Peter; Ligtenberg, Marjolijn J. L.; Wijnen, Juul T.; Tops, Carli M. J.

Monoallelic PMS2 germline mutations cause 5%-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA- and RNA-based strategies are

Malaria in Brazil: what happens outside the Amazonian endemic region.

Science.gov (United States)

de Pina-Costa, Anielle; Brasil, Patrícia; Di Santi, Sílvia Maria; de Araujo, Mariana Pereira; Suárez-Mutis, Martha Cecilia; Santelli, Ana Carolina Faria e Silva; Oliveira-Ferreira, Joseli; Lourenço-de-Oliveira, Ricardo; Daniel-Ribeiro, Cláudio Tadeu

2014-08-01

Brazil, a country of continental proportions, presents three profiles of malaria transmission. The first and most important numerically, occurs inside the Amazon. The Amazon accounts for approximately 60% of the nation's territory and approximately 13% of the Brazilian population. This region hosts 99.5% of the nation's malaria cases, which are predominantly caused by Plasmodium vivax (i.e., 82% of cases in 2013). The second involves imported malaria, which corresponds to malaria cases acquired outside the region where the individuals live or the diagnosis was made. These cases are imported from endemic regions of Brazil (i.e., the Amazon) or from other countries in South and Central America, Africa and Asia. Imported malaria comprised 89% of the cases found outside the area of active transmission in Brazil in 2013. These cases highlight an important question with respect to both therapeutic and epidemiological issues because patients, especially those with falciparum malaria, arriving in a region where the health professionals may not have experience with the clinical manifestations of malaria and its diagnosis could suffer dramatic consequences associated with a potential delay in treatment. Additionally, because the Anopheles vectors exist in most of the country, even a single case of malaria, if not diagnosed and treated immediately, may result in introduced cases, causing outbreaks and even introducing or reintroducing the disease to a non-endemic, receptive region. Cases introduced outside the Amazon usually occur in areas in which malaria was formerly endemic and are transmitted by competent vectors belonging to the subgenus Nyssorhynchus (i.e., Anopheles darlingi, Anopheles aquasalis and species of the Albitarsis complex). The third type of transmission accounts for only 0.05% of all cases and is caused by autochthonous malaria in the Atlantic Forest, located primarily along the southeastern Atlantic Coast. They are caused by parasites that seem to be (or

Malaria in Brazil: what happens outside the Amazonian endemic region

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Anielle de Pina-Costa

2014-08-01

Full Text Available Brazil, a country of continental proportions, presents three profiles of malaria transmission. The first and most important numerically, occurs inside the Amazon. The Amazon accounts for approximately 60% of the nation’s territory and approximately 13% of the Brazilian population. This region hosts 99.5% of the nation’s malaria cases, which are predominantly caused by Plasmodium vivax (i.e., 82% of cases in 2013. The second involves imported malaria, which corresponds to malaria cases acquired outside the region where the individuals live or the diagnosis was made. These cases are imported from endemic regions of Brazil (i.e., the Amazon or from other countries in South and Central America, Africa and Asia. Imported malaria comprised 89% of the cases found outside the area of active transmission in Brazil in 2013. These cases highlight an important question with respect to both therapeutic and epidemiological issues because patients, especially those with falciparum malaria, arriving in a region where the health professionals may not have experience with the clinical manifestations of malaria and its diagnosis could suffer dramatic consequences associated with a potential delay in treatment. Additionally, because the Anopheles vectors exist in most of the country, even a single case of malaria, if not diagnosed and treated immediately, may result in introduced cases, causing outbreaks and even introducing or reintroducing the disease to a non-endemic, receptive region. Cases introduced outside the Amazon usually occur in areas in which malaria was formerly endemic and are transmitted by competent vectors belonging to the subgenus Nyssorhynchus (i.e., Anopheles darlingi, Anopheles aquasalis and species of the Albitarsis complex. The third type of transmission accounts for only 0.05% of all cases and is caused by autochthonous malaria in the Atlantic Forest, located primarily along the southeastern Atlantic Coast. They are caused by parasites

Caracterização e relacionamento antigênico de três novos Bunyavirus no grupo Anopheles A (Bunyaviridae dos arbovirus Characterization and antigenic relationship of three new Bunyavirus in the Anopheles A serogroup (Bunyaviridae of arboviruses

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Jorge Fernando Soares Travassos da Rosa

1992-06-01

Full Text Available São descritos o isolamento e a caracterização de três novos arbovirus isolados na região da Usina Hidro-Elétrica de Tucuruí (UHE-TUC. Os três novos arbovirus pertencem ao grupo Anopheles A(ANA, gênero Bunyavirus (família Bunyaviridae. Os vírus Tucuruí (TUC, Caraipé (CPE e Arumateua (ART são relacionados entre si e com o vírus Trombetas (TBT, formando dentro do grupo ANA um complexo chamado Trombetas. Os arbovirus TUC, CPE e ART foram obtidos a partir de lotes de mosquitos Anopheles (Nyssorhynchus sp capturados em Tucuruí, nas proximidades da usina hidrelétrica de Tucuruí, Estado do Pará, nos meses de fevereiro, agosto e outubro de 1984, respectivamente. Até o final de 1990 os vírus TUC, CPE e ART foram isolados 12, 32 e 28 vezes respectivamente, sempre na região da UHE-TUC, exceção feita ao vírus TUC, do qual se obteve uma amostra procedente de Balbina, onde também foi construída uma hidroelétrica. Até o presente, esses vírus só foram isolados a partir de mosquitos do grupo An. (Nys. principalmente, a partir das espécies An. (Nys. nuneztovari e An. (Nys. triannulatus também consideradas vetores secundários da malária na Amazônia Brasileira. Testes sorológicos executados com soros humanos e de diversas espécies de animais silvestres foram negativos, com exceção de um soro de um carnívoro de espécie Nasua nasua que neutralizou a amostra TUC em títulos de 2.6 índice logaritmico de neutralização (ILN.The isolation and characterization of three new viruses obtained from the Tucuruí hydroelectric dam region is repeated. These three agents belong to the Anopheles A serogroup, genus Bunyavirus, Bunyaviridae. The Tucuruí (TUC, Caraipe (CPE and Arumateua (ART viruses have close relationships with each other and with Trombetas (TBT virus, an Anopheles A virus previously isolated in the Amazon Region of Brazil. These viruses form the "Trombetas complex". TUC, CPE and ART viruses were obtained from pools of

Habitat suitability of Anopheles vector species and association with human malaria in the Atlantic Forest in south-eastern Brazil.

Science.gov (United States)

Laporta, Gabriel Zorello; Ramos, Daniel Garkauskas; Ribeiro, Milton Cezar; Sallum, Maria Anice Mureb

2011-08-01

Every year, autochthonous cases of Plasmodium vivax malaria occur in low-endemicity areas of Vale do Ribeira in the south-eastern part of the Atlantic Forest, state of São Paulo, where Anopheles cruzii and Anopheles bellator are considered the primary vectors. However, other species in the subgenus Nyssorhynchus of Anopheles (e.g., Anopheles marajoara) are abundant and may participate in the dynamics of malarial transmission in that region. The objectives of the present study were to assess the spatial distribution of An. cruzii, An. bellator and An. marajoara and to associate the presence of these species with malaria cases in the municipalities of the Vale do Ribeira. Potential habitat suitability modelling was applied to determine both the spatial distribution of An. cruzii, An. bellator and An. marajoara and to establish the density of each species. Poisson regression was utilized to associate malaria cases with estimated vector densities. As a result, An. cruzii was correlated with the forested slopes of the Serra do Mar, An. bellator with the coastal plain and An. marajoara with the deforested areas. Moreover, both An. marajoara and An. cruzii were positively associated with malaria cases. Considering that An. marajoara was demonstrated to be a primary vector of human Plasmodium in the rural areas of the state of Amapá, more attention should be given to the species in the deforested areas of the Atlantic Forest, where it might be a secondary vector.

A putative Lynch syndrome family carrying MSH2 and MSH6 variants of uncertain significance-functional analysis reveals the pathogenic one

DEFF Research Database (Denmark)

Kantelinen, Jukka; Hansen, Thomas V O; Kansikas, Minttu

2011-01-01

Inherited pathogenic mutations in the mismatch repair (MMR) genes, MSH2, MLH1, MSH6, and PMS2 predispose to Lynch syndrome (LS). However, the finding of a variant or variants of uncertain significance (VUS) in affected family members complicates the risk assessment. Here, we describe a putative LS...

Human skin emanations in the host-seeking behaviour of the malaria mosquito Anopheles gambiae

NARCIS (Netherlands)

Braks, M.

1999-01-01

Malaria is an infectious disease caused by a parasite ( Plasmodium spp.) that is transmitted between human individuals by mosquitoes, belonging to the order of insects, Diptera, family of Culicidae (mosquitoes) and genus of Anopheles (malaria

The practical importance of permanent and semipermanent habitats for controlling aquatic stages of Anopheles gambiae sensu lato mosquitoes: operational observations from a rural town in western Kenya

NARCIS (Netherlands)

Fillinger, U.; Sonye, G.; Killeen, G.F.; Knols, B.G.J.; Becker, N.

2004-01-01

Control of aquatic-stage Anopheles is one of the oldest and most historically successful interventions to prevent malaria, but it has seen little application in Africa. Consequently, the ecology of immature afrotropical Anopheles has received insufficient attention. We therefore examined the

Presence of the mosquito Anopheles hyrcanus in South Moravia, Czech Republic

Czech Academy of Sciences Publication Activity Database

Šebesta, Oldřich; Rettich, F.; Minář, Jan; Halouzka, Jiří; Hubálek, Zdeněk; Juřicová, Zina; Rudolf, Ivo; Šikutová, Silvie; Gelbič, Ivan; Reiter, P.

2009-01-01

Roč. 23, č. 3 (2009), s. 284-286 ISSN 0269-283X R&D Projects: GA MŠk 2B08003 EU Projects: European Commission(XE) 10284 - EDEN Institutional research plan: CEZ:AV0Z60930519; CEZ:AV0Z50070508 Keywords : Anopheles hyrcanus * mosquitoes * geographic range * Central Europe Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 2.092, year: 2009

Cryptic species Anopheles daciae (Diptera: Culicidae) found in the Czech Republic and Slovakia

Czech Academy of Sciences Publication Activity Database

Blažejová, Hana; Šebesta, Oldřich; Rettich, F.; Mendel, Jan; Čabanová, V.; Miterpáková, M.; Betášová, Lenka; Peško, Juraj; Hubálek, Zdeněk; Kampen, H.; Rudolf, Ivo

2018-01-01

Roč. 117, č. 1 (2018), s. 315-321 ISSN 0932-0113 R&D Projects: GA ČR(CZ) GA16-20054S Institutional support: RVO:68081766 Keywords : Anophelinae * Maculipennis complex * Anopheles daciae * Mosquitoes * Cryptic species * Vector-borne diseases Subject RIV: EG - Zoology Impact factor: 2.329, year: 2016

Feeding and survival of the malaria vector Anopheles gambiae on plants growing in Kenia

NARCIS (Netherlands)

Impoinvil, D.E.; Kongere, J.O.; Foster, W.A.; Njiru, B.N.; Killeen, G.F.; Githure, J.I.; Beier, J.C.; Hassanali, A.; Knols, B.G.J.

2004-01-01

The propensity of the malaria vector mosquito Anopheles gambiae Giles (Diptera: Culicidae) to ingest sugars from various plants, and subsequent survival rates, were assessed with laboratory-reared males and females offered eight species of plants commonly cultivated and/or growing wild in western

Spatial repellency screening in a high-throughput apparatus with Aedes aegypti and Anopheles gambiae

Science.gov (United States)

Spatial repellents are essential for personal protection against mosquitoes, such as Aedes aegypti and Anopheles gambiae, to reduce annoyance biting and transmission of mosquito-borne diseases. The number of safe and effective repellents, including DEET, picaridin, and IR3535, is limited and contin...

Host feeding patterns and preference of Anopheles minimus (Diptera: Culicidae) in a malaria endemic area of western Thailand: baseline site description.

Science.gov (United States)

Tisgratog, Rungarun; Tananchai, Chatchai; Juntarajumnong, Waraporn; Tuntakom, Siripun; Bangs, Michael J; Corbel, Vincent; Chareonviriyaphap, Theeraphap

2012-06-07

Host feeding patterns of Anopheles minimus in relation to ambient environmental conditions were observed during a 2-year period at Tum Sua Village, located in Mae Sot District, Tak Province, in western Thailand, where An. minimus is found in abundance and regarded as the most predominant malaria vector species. Detailed information on mosquito behavior is important for understanding the epidemiology of disease transmission and developing more effective and efficient vector control methods. Adult mosquitoes were collected every 2 months for two consecutive nights from 1800 to 0600 hrs. Three collection methods were used; indoor human-landing collections (HLC), outdoor HLC, and outdoor cattle-bait collections (CBC). A total of 7,663 female Anopheles mosquitoes were collected of which 5,392 were identified as members of 3 different species complexes, the most prevalent being Anopheles minimus complex (50.36%), followed by Anopheles maculatus complex (19.68%) and Anopheles dirus complex (0.33%). An. minimus s.s. comprised virtually all (> 99.8 percent) of Minimus Complex species captured. Blood feeding behavior of An. minimus was more pronounced during the second half of the evening, showing a slight preference to blood feed outdoors (~60%) versus inside structures. Significantly (P feeding behavior. Although a significant difference in total number of mosquitoes from the HLC was recorded between the first and second year, the mean biting frequency over the course of the evening hours remained similar. The Human landing activity of An. minimus in Tum Sua Village showed a stronger preference/attraction for humans compared to a cow-baited collection method. This study supports the incrimination of An. minimus as the primary malaria vector in the area. A better understanding of mosquito behavior related to host preference, and the temporal and spatial blood feeding activity will help facilitate the design of vector control strategies and effectiveness of vector

Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency (CMMRD) Syndrome

NARCIS (Netherlands)

van der Klift, Heleen M; Mensenkamp, Arjen R; Drost, Mark; Bik, Elsa C; Vos, Yvonne J; Gille, Hans J J P; Redeker, Bert E J W; Tiersma, Yvonne; Zonneveld, José B M; García, Encarna Gómez; Letteboer, Tom G W; Olderode-Berends, Maran J W; van Hest, Liselotte P; van Os, Theo A; Verhoef, Senno; Wagner, Anja; van Asperen, Christi J; Ten Broeke, Sanne W; Hes, Frederik J; de Wind, Niels; Nielsen, Maartje; Devilee, Peter; Ligtenberg, Marjolijn J L; Wijnen, Juul T; Tops, Carli M J

2016-01-01

Monoallelic PMS2 germline mutations cause 5-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional MMR deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA and RNA-based strategies are applied to

Role of Anopheles (Kerteszia bellator as malaria vector in Southeastern Brazil (Diptera: Culicidae

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Oswaldo Paulo Forattini

1999-11-01

Full Text Available New research concerning Anopheles bellator in the southeast of the State of São Paulo, Brazil, are reported. Adult females of this mosquito showed remarkable endophily and endophagy which was even greater than An. cruzii. The epidemiological role of this anopheline as a malaria vector is discussed.

Long non-coding RNA discovery across the genus anopheles reveals conserved secondary structures within and beyond the Gambiae complex.

Science.gov (United States)

Jenkins, Adam M; Waterhouse, Robert M; Muskavitch, Marc A T

2015-04-23

Long non-coding RNAs (lncRNAs) have been defined as mRNA-like transcripts longer than 200 nucleotides that lack significant protein-coding potential, and many of them constitute scaffolds for ribonucleoprotein complexes with critical roles in epigenetic regulation. Various lncRNAs have been implicated in the modulation of chromatin structure, transcriptional and post-transcriptional gene regulation, and regulation of genomic stability in mammals, Caenorhabditis elegans, and Drosophila melanogaster. The purpose of this study is to identify the lncRNA landscape in the malaria vector An. gambiae and assess the evolutionary conservation of lncRNAs and their secondary structures across the Anopheles genus. Using deep RNA sequencing of multiple Anopheles gambiae life stages, we have identified 2,949 lncRNAs and more than 300 previously unannotated putative protein-coding genes. The lncRNAs exhibit differential expression profiles across life stages and adult genders. We find that across the genus Anopheles, lncRNAs display much lower sequence conservation than protein-coding genes. Additionally, we find that lncRNA secondary structure is highly conserved within the Gambiae complex, but diverges rapidly across the rest of the genus Anopheles. This study offers one of the first lncRNA secondary structure analyses in vector insects. Our description of lncRNAs in An. gambiae offers the most comprehensive genome-wide insights to date into lncRNAs in this vector mosquito, and defines a set of potential targets for the development of vector-based interventions that may further curb the human malaria burden in disease-endemic countries.

Control of pyrethroid-resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes with chlorfenapyr in Benin

NARCIS (Netherlands)

N'Guessan, R.; Boko, P.; Odjo, A.; Knols, B.G.J.; Akogbeto, M.; Rowland, M.

2009-01-01

Objective To compare the efficacy of chlorfenapyr applied on mosquito nets and as an indoor residual spray against populations of Anopheles gambiae and Culex quinquefasciatus in an area of Benin that shows problematic levels of pyrethroid resistance. Method Eight-week trial conducted in experimental

Spatio-temporal variations of Anopheles coluzzii and An. gambiae and their Plasmodium infectivity rates in Lobito, Angola.

Science.gov (United States)

Carnevale, Pierre; Toto, Jean-Claude; Besnard, Patrick; Santos, Maria Adelaide Dos; Fortes, Filomeno; Allan, Richard; Manguin, Sylvie

2015-06-01

From 2003 to 2007, entomological surveys were conducted in Lobito town (Benguela Province, Angola) to determine which Anopheles species were present and to identify the vectors responsible for malaria transmission in areas where workers of the Sonamet Company live. Two types of surveys were conducted: (1) time and space surveys in the low and upper parts of Lobito during the rainy and dry periods; (2) a two-year longitudinal study in Sonamet workers' houses provided with long-lasting insecticide-treated nets (LLIN), "PermaNet," along with the neighboring community. Both species, An. coluzzii (M molecular form) and An. gambiae (S molecular form), were collected. Anopheles coluzzii was predominant during the dry season in the low part of Lobito where larvae develop in natural ponds and temporary pools. However, during the rainy season, An. gambiae was found in higher proportions in the upper part of the town where larvae were collected in domestic water tanks built near houses. Anopheles melas and An. listeri were captured in higher numbers during the dry season and in the low part of Lobito where larvae develop in stagnant brackish water pools. The infectivity rates of An. gambiae s.l. varied from 0.90% to 3.41%. © 2015 The Society for Vector Ecology.

Quantification of sequence exchange events between PMS2 and PMS2CL provides a basis for improved mutation scanning of Lynch syndrome patients.

NARCIS (Netherlands)

Klift, H.M. van der; Tops, C.M.; Bik, E.C.; Boogaard, M.W.; Borgstein, A.M.; Hansson, K.B.; Ausems, M.G.E.M.; Gomez Garcia, E.; Green, A.; Hes, F.J.; Izatt, L.; Hest, L.P. van; Alonso, A.M.; Vriends, A.H.; Wagner, A.; Zelst-Stams, W.A.G. van; Vasen, H.F.; Morreau, H.; Devilee, P.; Wijnen, J.T.

2010-01-01

Heterozygous mutations in PMS2 are involved in Lynch syndrome, whereas biallelic mutations are found in Constitutional mismatch repair-deficiency syndrome patients. Mutation detection is complicated by the occurrence of sequence exchange events between the duplicated regions of PMS2 and PMS2CL. We

Efficacy of proximal colectomy for surgical management of right-sided first colorectal cancer in Lynch Syndrome mutation carriers.

Science.gov (United States)

Hiatt, Molly J; Casey, Murray Joseph; Lynch, Henry T; Snyder, Carrie L; Stacey, Mark; Walters, Ryan W

2017-11-08

This study analyzes the occurrence of colorectal cancer (CRC) in Lynch syndrome (LS) mutation carriers, interval until diagnosis of metachronous CRC, and survival after proximal colectomy (PC) compared with total (TC) and subtotal colectomy (STC) for right-sided first CRC in LS mutation carriers. Sixty-four LS mutation carriers with right-sided first CRC treated with PC or TC + STC were confirmed by clinical records. Bivariate analyses were examined for significance and life tables were generated for risk of metachronous CRC and survival estimates following surgery. One of 16 (6.3%) mutation carriers treated with TC + STC developed subsequent CRC compared with 13/48 (27%) treated by PC. There was no significant difference in survival estimates between PC compared with TC + STC through 25 years after surgery. Risk of subsequent CRC and survival estimates following PC and TC + STC should be considered in surgical management of right-sided first CRC in LS mutation carriers. Lynch syndrome mutation carriers are still at 27% risk for metachronous colorectal cancer after proximal colectomy for right-sided first colorectal cancers, but this study found no difference in survival through 25 years follow-up compared with those treated with total and subtotal colectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

Comportamiento estacional del Anopheles (nyssorhynchus darlingi root 1926 en localidades de Loreto y Madre de Dios, Perú 1999- 2000

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Walter León C

2003-03-01

Full Text Available Objetivos: Determinar el comportamiento estacional del Anopheles darlingi en las localidades de Santa Clara (Loreto y Villa Luz (Madre de Dios. Materiales y métodos: En las localidades de Santa Clara y Villa Luz, entre agosto de 1999 y junio de 2000 se realizó mensualmente la inspección de criaderos, colecta de larvas de Anopheles darlingi por el método del cucharón y colecta de mosquitos adultos por el método cebo humano (intradomicilio y peri domicilió, trampa Shannon y refugio animal (extradomicilio. Se calcularon los indicadores: criadero positivo y densidad larvaria por cucharonada, índice de picadura hombre noche (IPHN, índice de picadura hombre hora (IPHH, índice esporozoítico y tasa de paridad. Resultados: El IPHN en ambas localidades se incrementó en la estación lluviosa con los valores más altos en mayo (Santa Clara y febrero (Villa Luz. En Santa Clara, el comportamiento de la picadura del Anopheles darlingi de agosto a diciembre de 1999, fue unimodal presentándose el pico de IPHH entre las 19.00 y 21.00 horas; sin embargo, de marzo a junio de 2000, el comportamiento fue bimodal con dos picos del IPHH: entre las 19.00 y 22.00 horas, y entre las 2.00 y 4.00 horas. En Villa Luz, el comportamiento de la picadura, de agosto a junio de 1999, se mantuvo unimodal, con el pico de IPHH entre las 21.00 y 24.00 horas. Las especies inmaduras de Anopheles darlingi representaron menos del 20% de las larvas encontradas en los criaderos permanentes. Conclusiones: El Anopheles darlingi presenta mayor densidad poblacional en meses de estación lluviosa, con comportamientos de picadura distintos según localidad y estación. Los criaderos evaluados no serían criaderos tan importantes de esta especie.

Bionomics of the malaria vector Anopheles farauti in Temotu Province, Solomon Islands: issues for malaria elimination

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Mackenzie Donna O

2011-05-01

Full Text Available Abstract Background In the Solomon Islands, the Malaria Eradication Programmes of the 1970s virtually eliminated the malaria vectors: Anopheles punctulatus and Anopheles koliensis, both late night biting, endophagic species. However, the vector, Anopheles farauti, changed its behaviour to bite early in the evening outdoors. Thus, An. farauti mosquitoes were able to avoid insecticide exposure and still maintain transmission. Thirty years on and the Solomon Islands are planning for intensified malaria control and localized elimination; but little is currently known about the behaviour of the vectors and how they will respond to intensified control. Methods In the elimination area, Temotu Province, standard entomological collection methods were conducted in typical coastal villages to determine the vector, its ecology, biting density, behaviour, longevity, and vector efficacy. These vector surveys were conducted pre-intervention and post-intervention following indoor residual spraying and distribution of long-lasting insecticidal nets. Results Anopheles farauti was the only anopheline in Temotu Province. In 2008 (pre-intervention, this species occurred in moderate to high densities (19.5-78.5 bites/person/night and expressed a tendency to bite outdoors, early in the night (peak biting time 6-8 pm. Surveys post intervention showed that there was little, if any, reduction in biting densities and no reduction in the longevity of the vector population. After adjusting for human behaviour, indoor biting was reduced from 57% pre-intervention to 40% post-intervention. Conclusion In an effort to learn from historical mistakes and develop successful elimination programmes, there is a need for implementing complimentary vector control tools that can target exophagic and early biting vectors. Intensified indoor residual spraying and long-lasting insecticide net use has further promoted the early, outdoor feeding behaviour of An. farauti in the Solomon Islands

Anopheles larval abundance and diversity in three rice agro-village complexes Mwea irrigation scheme, central Kenya

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Mwangangi Joseph M

2010-08-01

Full Text Available Abstract Background The diversity and abundance of Anopheles larvae has significant influence on the resulting adult mosquito population and hence the dynamics of malaria transmission. Studies were conducted to examine larval habitat dynamics and ecological factors affecting survivorship of aquatic stages of malaria vectors in three agro-ecological settings in Mwea, Kenya. Methods Three villages were selected based on rice husbandry and water management practices. Aquatic habitats in the 3 villages representing planned rice cultivation (Mbui Njeru, unplanned rice cultivation (Kiamachiri and non-irrigated (Murinduko agro-ecosystems were sampled every 2 weeks to generate stage-specific estimates of mosquito larval densities, relative abundance and diversity. Records of distance to the nearest homestead, vegetation coverage, surface debris, turbidity, habitat stability, habitat type, rice growth stage, number of rice tillers and percent Azolla cover were taken for each habitat. Results Captures of early, late instars and pupae accounted for 78.2%, 10.9% and 10.8% of the total Anopheles immatures sampled (n = 29,252, respectively. There were significant differences in larval abundance between 3 agro-ecosystems. The village with 'planned' rice cultivation had relatively lower Anopheles larval densities compared to the villages where 'unplanned' or non-irrigated. Similarly, species composition and richness was higher in the two villages with either 'unplanned' or limited rice cultivation, an indication of the importance of land use patterns on diversity of larval habitat types. Rice fields and associated canals were the most productive habitat types while water pools and puddles were important for short periods during the rainy season. Multiple logistic regression analysis showed that presence of other invertebrates, percentage Azolla cover, distance to nearest homestead, depth and water turbidity were the best predictors for Anopheles mosquito larval

Gene expression changes in the salivary glands of Anopheles coluzzii elicited by Plasmodium berghei infection

Czech Academy of Sciences Publication Activity Database

Pinheiro-Silva, R.; Borges, L.; Coelho, L.P.; Cabezas-Cruz, A.; Valdés, James J.; do Rosário, V.; de la Fuente, J.; Domingos, A.

2015-01-01

Roč. 8, SEP 23 2015 (2015), s. 485 ISSN 1756-3305 Institutional support: RVO:60077344 Keywords : Anopheles coluzzii * Salivary glands * Plasmodium berghei * Sporozoite * RNA-seq * Glucose transporter * RNAi Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2015

Development of in vitro and in vivo functional assays to enable diagnosis of Variants of Uncertain Significance in the common cancer predisposition Lynch syndrome

NARCIS (Netherlands)

Drost, Mark

2014-01-01

Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose

Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study

NARCIS (Netherlands)

Jung, A.Y.; van Duijnhoven, F.J.B.; Nagengast, F.M.; Botma, A.; Heine-Broring, R.C.; Kleibeuker, J.H.; Vasen, H.F.A.; Harryvan, J.L.; Winkels, R.M.; Kampman, E.

2014-01-01

Purpose: Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given

Wide cross-reactivity between Anopheles gambiae and Anopheles funestus SG6 salivary proteins supports exploitation of gSG6 as a marker of human exposure to major malaria vectors in tropical Africa

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Petrarca Vincenzo

2011-07-01

Full Text Available Abstract Background The Anopheles gambiae gSG6 is an anopheline-specific salivary protein which helps female mosquitoes to efficiently feed on blood. Besides its role in haematophagy, gSG6 is immunogenic and elicits in exposed individuals an IgG response, which may be used as indicator of exposure to the main African malaria vector A. gambiae. However, malaria transmission in tropical Africa is sustained by three main vectors (A. gambiae, Anopheles arabiensis and Anopheles funestus and a general marker, reflecting exposure to at least these three species, would be especially valuable. The SG6 protein is highly conserved within the A. gambiae species complex whereas the A. funestus homologue, fSG6, is more divergent (80% identity with gSG6. The aim of this study was to evaluate cross-reactivity of human sera to gSG6 and fSG6. Methods The A. funestus SG6 protein was expressed/purified and the humoral response to gSG6, fSG6 and a combination of the two antigens was compared in a population from a malaria hyperendemic area of Burkina Faso where both vectors were present, although with a large A. gambiae prevalence (>75%. Sera collected at the beginning and at the end of the high transmission/rainy season, as well as during the following low transmission/dry season, were analysed. Results According to previous observations, both anti-SG6 IgG level and prevalence decreased during the low transmission/dry season and showed a typical age-dependent pattern. No significant difference in the response to the two antigens was found, although their combined use yielded in most cases higher IgG level. Conclusions Comparative analysis of gSG6 and fSG6 immunogenicity to humans suggests the occurrence of a wide cross-reactivity, even though the two proteins carry species-specific epitopes. This study supports the use of gSG6 as reliable indicator of exposure to the three main African malaria vectors, a marker which may be useful to monitor malaria transmission

Role of microsatellite instability-low as a diagnostic biomarker of Lynch syndrome in colorectal cancer.

Science.gov (United States)

Vilar, Eduardo; Mork, Maureen E; Cuddy, Amanda; Borras, Ester; Bannon, Sarah A; Taggart, Melissa W; Ying, Jun; Broaddus, Russell R; Luthra, Rajyalakshmi; Rodriguez-Bigas, Miguel A; Lynch, Patrick M; You, Yi-Qian Nancy

2014-01-01

Lynch syndrome is the most common Mendelian disorder predisposing persons to hereditary colorectal cancer. Carriers of MSH6 mutations constitute less than 10% of the total of cases with Lynch syndrome and present with a weaker clinical phenotype, including low levels of microsatellite instability (MSI-L) in colorectal tumors. The frequency of MSH6 mutation carriers among patients presenting with MSI-L colorectal cancer has yet to be determined, as has the appropriate genetic workup in this context. We have reviewed here the clinicopathologic characteristics, immunohistochemistry, and genetic testing results for 71 patients at a single institution diagnosed with MSI-L colorectal cancers. Of 71 patients with MSI-L tumors, 21 underwent genetic testing for MSH6 mutations, three of whom presented with loss of staining of MSH6 and only one of whom carried a pathogenic germline MSH6 mutation in exon 4 (c.2677_2678delCT; p.Leu893Alafs*6). This latter patient had a significant family history of cancer and had a rectal primary tumor that showed instability only in mononucleotide markers. In this cohort of MSI-L patients, we detected no notable clinicopathologic or molecular characteristic that would help to distinguish a group most likely to harbor germline MSH6 mutations. Therefore, we conclude that the prevalence of MSH6 mutations among patients with MSI-L tumors is very low. Microsatellite instability analysis combined with immunohistochemistry of mismatch repair proteins adequately detects potential MSH6 mutation carriers among MSI-L colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

Thermal limits of wild and laboratory strains of two African malaria vector species, Anopheles arabiensis and Anopheles funestus

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Lyons Candice L

2012-07-01

Full Text Available Abstract Background Malaria affects large parts of the developing world and is responsible for almost 800,000 deaths annually. As climates change, concerns have arisen as to how this vector-borne disease will be impacted by changing rainfall patterns and warming temperatures. Despite the importance and controversy surrounding the impact of climate change on the potential spread of this disease, little information exists on the tolerances of several of the vector species themselves. Methods Using a ramping protocol (to assess critical thermal limits - CT and plunge protocol (to assess lethal temperature limits - LT information on the thermal tolerance of two of Africa’s important malaria vectors, Anopheles arabiensis and Anopheles funestus was collected. The effects of age, thermal acclimation treatment, sex and strain (laboratory versus wild adults were investigated for CT determinations for each species. The effects of age and sex for adults and life stage (larvae, pupae, adults were investigated for LT determinations. Results In both species, females are more tolerant to low and high temperatures than males; larvae and pupae have higher upper lethal limits than do adults. Thermal acclimation of adults has large effects in some instances but small effects in others. Younger adults tend to be more tolerant of low or high temperatures than older age groups. Long-standing laboratory colonies are sufficiently similar in thermal tolerance to field-collected animals to provide reasonable surrogates when making inferences about wild population responses. Differences between these two vectors in their thermal tolerances, especially in larvae and pupae, are plausibly a consequence of different habitat utilization. Conclusions Limited plasticity is characteristic of the adults of these vector species relative to others examined to date, suggesting limited scope for within-generation change in thermal tolerance. These findings and the greater tolerance

Population genetics of the malaria vector Anopheles aconitus in China and Southeast Asia.

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Chen, Bin; Harbach, Ralph E; Walton, Catherine; He, Zhengbo; Zhong, Daibin; Yan, Guiyun; Butlin, Roger K

2012-12-01

Anopheles aconitus is a well-known vector of malaria and is broadly distributed in the Oriental Region, yet there is no information on its population genetic characteristics. In this study, the genetic differentiation among populations was examined using 140 mtDNA COII sequences from 21 sites throughout Southern China, Myanmar, Vietnam, Thailand, Laos and Sri Lanka. The population in Sri Lanka has characteristic rDNA D3 and ITS2, mtDNA COII and ND5 haplotypes, and may be considered a distinct subspecies. Clear genetic structure was observed with highly significant genetic variation present among population groups in Southeast Asia. The greatest genetic diversity exists in Yunnan and Myanmar population groups. All population groups are significantly different from one another in pairwise Fst values, except Northern Thailand with Central Thailand. Mismatch distributions and extremely significant F(s) values suggest that the populations passed through a recent demographic expansion. These patterns are discussed in relation to the likely biogeographic history of the region and compared to other Anopheles species. Copyright © 2012 Elsevier B.V. All rights reserved.

A Revision of the Argyritarsis Section of the Subgenus Nyssorhynchus of Anopheles (Diptera: Culicidae)

Science.gov (United States)

1988-01-01

genero Nyssorhynchus, corn especial referencia a morfologia dos ovos. Rev. Biol. Hyg. 9:51- 60. 1938b. Observacoes sobre o ciclo evolutivo de Anopheles...Vale do Paraiba. Nova variedade e ciclo evolutivo do Anofeles (Nyssorhynchus) osvaldoi var. ayrozai n. var. Ann. Paul. Med. Cir. 40:377-392. 1940b

Description and Comparison of Morphological Structures of the Eggs of Anopheles Hyrcanus Group and Related Species (Diptera: Culicidae) from the Republic of Korea

Science.gov (United States)

2009-10-20

major vector of malaria in China ; however, its vectorial capacity is unknown in the ROK. The other remaining four Anopheles species are not considered to...morphometry and morphology of Anopheles aconitus Form B and C eggs under scanning electron microscope. Revista do Instituto de Medicina Tropical de Sao Paulo...and its genetic identity with An. (Ano.) anthropophagus from China (Diptera: Culicidae). Zootaxa, 378, 1–14. RUEDA ET AL.40 · Zootaxa 2268 © 2009

Improvement of a synthetic lure for Anopheles gambiae using compounds produced by human skin microbiota

NARCIS (Netherlands)

Verhulst, N.O.; Mbadi, P.A.; Bukovinszkine-Kiss, G.; Mukabana, W.R.; Loon, van J.J.A.; Takken, W.; Smallegange, R.C.

2011-01-01

Background - Anopheles gambiae sensu stricto is considered to be highly anthropophilic and volatiles of human origin provide essential cues during its host-seeking behaviour. A synthetic blend of three human-derived volatiles, ammonia, lactic acid and tetradecanoic acid, attracts A. gambiae. In

Mitochondrial genomes of Anopheles arabiensis, An.gambiae and An.coluzzii show no clear species division

Science.gov (United States)

Here we report the complete mitochondrial sequences of 70 individual field collected mosquito specimens from throughout Sub-Saharan Africa. We generated this dataset to identify species specific markers for the following Anopheles species and chromosomal forms: An.arabiensis, An.coluzzii (The Forest...

Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer : a report from the prospective Lynch syndrome database

NARCIS (Netherlands)

Møller, Pål; Seppälä, Toni; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Evans, D Gareth; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind; Rødland, Einar Andreas; Tharmaratnam, Kukatharmini; de Vos Tot Nederveen Cappel, Wouter H; Hill, James; Wijnen, Juul; Jenkins, Mark; Green, Kate; Lalloo, Fiona; Sunde, Lone; Mints, Miriam; Bertario, Lucio; Pineda, Marta; Navarro, Matilde; Morak, Monika; Renkonen-Sinisalo, Laura; Frayling, Ian M; Plazzer, John-Paul; Pylvanainen, Kirsi; Genuardi, Maurizio; Mecklin, Jukka-Pekka; Möslein, Gabriela; Sampson, Julian R; Capella, Gabriel

2016-01-01

Objective Today most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do

Impact of Diurnal Temperature Fluctuations during Larval Development on Adult Life History Traits and Insecticide Susceptibility in Two Vectors; Anopheles gambiae and Aedes aegypti

Science.gov (United States)

2014-04-30

ANOPHELES GAMBIAE AND AEDES AEGYPTI. by Jeffrey W. Clark Dissertation submitted to the Faculty of the Department of Preventive Medicine and...Vectors; Anopheles gambiae and Aedes aegypti." Name of Candidate: Jeffrey Clark Doctor of Philosophy Degree April 30, 2014 DISSERTATION AND ABSTRACT...for the many fruitful discussions and the standing offer to help whenever I needed it; and to Joe Wagman, for providing needed Aedes aegypti eggs from

Insertion polymorphisms of SINE200 retrotransposons within speciation islands of Anopheles gambiae molecular forms

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Tu Zhijian

2008-08-01

Full Text Available Abstract Background SINEs (Short INterspersed Elements are homoplasy-free and co-dominant genetic markers which are considered to represent useful tools for population genetic studies, and could help clarifying the speciation processes ongoing within the major malaria vector in Africa, Anopheles gambiae s.s. Here, we report the results of the analysis of the insertion polymorphism of a nearly 200 bp-long SINE (SINE200 within genome areas of high differentiation (i.e. "speciation islands" of M and S A. gambiae molecular forms. Methods A SINE-PCR approach was carried out on thirteen SINE200 insertions in M and S females collected along the whole range of distribution of A. gambiae s.s. in sub-Saharan Africa. Ten specimens each for Anopheles arabiensis, Anopheles melas, Anopheles quadriannulatus A and 15 M/S hybrids from laboratory crosses were also analysed. Results Eight loci were successfully amplified and were found to be specific for A. gambiae s.s.: 5 on 2L chromosome and one on X chromosome resulted monomorphic, while two loci positioned respectively on 2R (i.e. S200 2R12D and X (i.e. S200 X6.1 chromosomes were found to be polymorphic. S200 2R12D was homozygote for the insertion in most S-form samples, while intermediate levels of polymorphism were shown in M-form, resulting in an overall high degree of genetic differentiation between molecular forms (Fst = 0.46 p S200 X6.1 was found to be fixed in all M- and absent in all S-specimens. This led to develop a novel easy-to-use PCR approach to straightforwardly identify A. gambiae molecular forms. This novel approach allows to overcome the constraints associated with markers on the rDNA region commonly used for M and S identification. In fact, it is based on a single copy and irreversible SINE200 insertion and, thus, is not subjected to peculiar evolutionary patterns affecting rDNA markers, e.g. incomplete homogenization of the arrays through concerted evolution and/or mixtures of M and S IGS

Host feeding patterns and preference of Anopheles minimus (Diptera: Culicidae in a malaria endemic area of western Thailand: baseline site description

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Tisgratog Rungarun

2012-06-01

Full Text Available Abstract Background Host feeding patterns of Anopheles minimus in relation to ambient environmental conditions were observed during a 2-year period at Tum Sua Village, located in Mae Sot District, Tak Province, in western Thailand, where An. minimus is found in abundance and regarded as the most predominant malaria vector species. Detailed information on mosquito behavior is important for understanding the epidemiology of disease transmission and developing more effective and efficient vector control methods. Methods Adult mosquitoes were collected every 2 months for two consecutive nights from 1800 to 0600 hrs. Three collection methods were used; indoor human-landing collections (HLC, outdoor HLC, and outdoor cattle-bait collections (CBC. Results A total of 7,663 female Anopheles mosquitoes were collected of which 5,392 were identified as members of 3 different species complexes, the most prevalent being Anopheles minimus complex (50.36%, followed by Anopheles maculatus complex (19.68% and Anopheles dirus complex (0.33%. An. minimus s.s. comprised virtually all (> 99.8 percent of Minimus Complex species captured. Blood feeding behavior of An. minimus was more pronounced during the second half of the evening, showing a slight preference to blood feed outdoors (~60% versus inside structures. Significantly (P An. minimus were collected from human-baited methods compared with a tethered cow, indicating a more anthropophilic feeding behavior. Although a significant difference in total number of mosquitoes from the HLC was recorded between the first and second year, the mean biting frequency over the course of the evening hours remained similar. Conclusions The Human landing activity of An. minimus in Tum Sua Village showed a stronger preference/attraction for humans compared to a cow-baited collection method. This study supports the incrimination of An. minimus as the primary malaria vector in the area. A better understanding of mosquito

Bionomics of Anopheles latens in Kapit, Sarawak, Malaysian Borneo in relation to the transmission of zoonotic simian malaria parasite Plasmodium knowlesi

Science.gov (United States)

Tan, Cheong H; Vythilingam, Indra; Matusop, Asmad; Chan, Seng T; Singh, Balbir

2008-01-01

Background A large focus of human infections with Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques was discovered in the Kapit Division of Sarawak, Malaysian Borneo. A study was initiated to identify the vectors of malaria, to elucidate where transmission is taking place and to understand the bionomics of the vectors in Kapit. Methods Three different ecological sites in the forest, farm and longhouse in the Kapit district were selected for the study. Mosquitoes were collected by human landing collection at all sites and at the forest also by monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites. Results and Discussions Over an 11-month period, a total of 2,504 Anopheles mosquitoes comprising 12 species were caught; 1,035 at the farm, 774 at the forest and 425 at the longhouse. Anopheles latens (62.3%) and Anopheles watsonii (30.6%) were the predominant species caught in the forested ecotypes, while in the farm Anopheles donaldi (49.9%) and An. latens (35.6%) predominated. In the long house, An. latens (29.6%) and An. donaldi (22.8%) were the major Anopheline species. However, An. latens was the only mosquito positive for sporozoites and it was found to be attracted to both human and monkey hosts. In monkey-baited net traps, it preferred to bite monkeys at the canopy level than at ground level. An. latens was found biting early as 18.00 hours. Conclusion Anopheles latens is the main vector for P. knowlesi malaria parasites in the Kapit District of Sarawak, Malaysian Borneo. The study underscores the relationship between ecology, abundance and bionomics of anopheline fauna. The simio-anthropophagic and acrodendrophilic behaviour of An. latens makes it an efficient vector for the transmission of P. knowlesi parasites to both human and monkey hosts. PMID:18377652

Bionomics of Anopheles latens in Kapit, Sarawak, Malaysian Borneo in relation to the transmission of zoonotic simian malaria parasite Plasmodium knowlesi

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Matusop Asmad

2008-03-01

Full Text Available Abstract Background A large focus of human infections with Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques was discovered in the Kapit Division of Sarawak, Malaysian Borneo. A study was initiated to identify the vectors of malaria, to elucidate where transmission is taking place and to understand the bionomics of the vectors in Kapit. Methods Three different ecological sites in the forest, farm and longhouse in the Kapit district were selected for the study. Mosquitoes were collected by human landing collection at all sites and at the forest also by monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites. Results and Discussions Over an 11-month period, a total of 2,504 Anopheles mosquitoes comprising 12 species were caught; 1,035 at the farm, 774 at the forest and 425 at the longhouse. Anopheles latens (62.3% and Anopheles watsonii (30.6% were the predominant species caught in the forested ecotypes, while in the farm Anopheles donaldi (49.9% and An. latens (35.6% predominated. In the long house, An. latens (29.6% and An. donaldi (22.8% were the major Anopheline species. However, An. latens was the only mosquito positive for sporozoites and it was found to be attracted to both human and monkey hosts. In monkey-baited net traps, it preferred to bite monkeys at the canopy level than at ground level. An. latens was found biting early as 18.00 hours. Conclusion Anopheles latens is the main vector for P. knowlesi malaria parasites in the Kapit District of Sarawak, Malaysian Borneo. The study underscores the relationship between ecology, abundance and bionomics of anopheline fauna. The simio-anthropophagic and acrodendrophilic behaviour of An. latens makes it an efficient vector for the transmission of P. knowlesi parasites to both human and monkey hosts.

Larvicidal effects of a neem (Azadirachta indica) oil formulation on the malaria vector Anopheles gambiae

NARCIS (Netherlands)

Okumu, F.O.; Knols, B.G.J.; Fillinger, U.

2007-01-01

Background - Larviciding is a key strategy used in many vector control programmes around the world. Costs could be reduced if larvicides could be manufactured locally. The potential of natural products as larvicides against the main African malaria vector, Anopheles gambiae s.s was evaluated.

Quantification of the efficiency of treatment of Anopheles gambiae breeding sites with petroleum products by local communities in areas of insecticide resistance in the Republic of Benin

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Doannio Julien MC MC

2007-05-01

Full Text Available Abstract Background The emergence of Anopheles populations capable of withstanding lethal doses of insecticides has weakened the efficacy of most insecticide based strategies of vector control and, has highlighted the need for developing new insecticidal molecules or, improving the efficacy of existing insecticides or abandoning those to which resistance has emerged. The use of petroleum products (PP against mosquito larvae had an immense success during early programmes of malaria control, but these compounds were abandoned and replaced in the 1950s by synthetic insecticides probably because of the high performances given by these new products. In the current context of vector resistance, it is important to elucidate the empirical use of PP by quantifying their efficiencies on resistant strains of Anopheles. Methods Larvae of Anopheles Ladji a local resistant strain were exposed to increasing concentrations of various PP (kerosene, petrol and engine oils for 24 hours and the lethal activities recorded. The highest concentration (HiC having no lethal activity (also referred as the NOEL or no effect level and the lowest concentration (LoC100 yielding 100% mortality were rated for each PP on the Ladji strain. Prior to laboratory analysis, KAP studies were conducted in three traditional communities were insecticide resistance is clearly established to confirm the use of PP against mosquitoes. Results Laboratory analysis of petrol, kerosene and engine oils, clearly established their lethal activities on resistant strains of Anopheles larvae. Contrary to existing references, this research revealed that exposed larvae of Anopheles were mostly killed by direct contact toxicity and not by suffocation as indicated in some earlier reports. Conclusion This research could serve as scientific basis to backup the empirical utilisation of PP on mosquito larvae and to envisage possibilities of using PP in some traditional settings where Anopheles have developed

HNPCC (Lynch Syndrome): Differential Diagnosis, Molecular Genetics and Management - a Review

Science.gov (United States)

2003-01-01

HNPCC (Lynch syndrome) is the most common form of hereditary colorectal cancer (CRC), wherein it accounts for between 2-7 percent of the total CRC burden. When considering the large number of extracolonic cancers integral to the syndrome, namely carcinoma of the endometrium, ovary, stomach, hepatobiliary system, pancreas, small bowel, brain tumors, and upper uroepithelial tract, these estimates of its frequency are likely to be conservative. The diagnosis is based upon its natural history in concert with a comprehensive cancer family history inclusive of all anatomic sites. In order for surveillance and management to be effective and, indeed, lifesaving, among these high-risk patients, the linchpin to cancer control would be the physician, who must be knowledgeable about hereditary cancer syndromes, their molecular and medical genetics, genetic counseling, and, most importantly, the natural history of the disorders, so that the entirety of this knowledge can be melded to highly-targeted management.

Change in Anopheles richness and composition in response to artificial flooding during the creation of the Jirau hydroelectric dam in Porto Velho, Brazil.

Science.gov (United States)

Rodrigures, Moreno S; Batista, Elis P; Silva, Alexandre A; Costa, Fábio M; Neto, Verissimo A S; Gil, Luiz Herman S

2017-02-22

Anopheles mosquitoes are the only vectors of human malaria. Anopheles species use standing water as breeding sites. Human activities, like the creation of an artificial lake during the implementation of hydroelectric power plants, lead to changes in environmental characteristics and, therefore, may changes the species richness and composition of Anopheles mosquitoes. The aim of the present study was to verify whether or not there is an association between the artificial flooding resulting from the construction of the Jirau hydroelectric power plant, and the richness and composition of anophelines. Mosquitoes samples were obtained monthly from the Jirau hydroelectric power plant area located at Porto Velho, Rondônia State, using Human Landing Catch (06:00-10:00 PM). Mosquitoes collected were transported to Laboratório de Entomologia Médica FIOCRUZ-RO where they were identified until species using dichotomous key. A total of 6347 anophelines belonging to eight different species were collected. The anophelines species richness was significantly lower during the first flooding stage. Differences in anophelines species composition were found when comparing the first flooding stage with the other stages. Furthermore, the mean number of Anopheles darlingi, the main vector of malaria in the region, increases during the first and the third flooding stages. The continual monitoring of these vectors during the late operational phase may be useful in order to understand how anophelines will behave in this area.

Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

Science.gov (United States)

Jansen, Anne M L; Geilenkirchen, Marije A; van Wezel, Tom; Jagmohan-Changur, Shantie C; Ruano, Dina; van der Klift, Heleen M; van den Akker, Brendy E W M; Laros, Jeroen F J; van Galen, Michiel; Wagner, Anja; Letteboer, Tom G W; Gómez-García, Encarna B; Tops, Carli M J; Vasen, Hans F; Devilee, Peter; Hes, Frederik J; Morreau, Hans; Wijnen, Juul T

2016-01-01

Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes.

Effects of fungal infection on feeding and survival of Anopheles gambiae (Diptera: Culicidae) on plant sugars

NARCIS (Netherlands)

Ondiaka, S.N.; Masinde, E.W.; Koenraadt, C.J.M.; Takken, W.; Mukabana, W.R.

2015-01-01

Background The entomopathogenic fungus Metarhizium anisopliae shows great promise for the control of adult malaria vectors. A promising strategy for infection of mosquitoes is supplying the fungus at plant feeding sites. Methods We evaluated the survival of fungus-exposed Anopheles gambiae

The effect of temperature on Anopheles mosquito population dynamics and the potential for malaria transmission.

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Lindsay M Beck-Johnson

Full Text Available The parasites that cause malaria depend on Anopheles mosquitoes for transmission; because of this, mosquito population dynamics are a key determinant of malaria risk. Development and survival rates of both the Anopheles mosquitoes and the Plasmodium parasites that cause malaria depend on temperature, making this a potential driver of mosquito population dynamics and malaria transmission. We developed a temperature-dependent, stage-structured delayed differential equation model to better understand how climate determines risk. Including the full mosquito life cycle in the model reveals that the mosquito population abundance is more sensitive to temperature than previously thought because it is strongly influenced by the dynamics of the juvenile mosquito stages whose vital rates are also temperature-dependent. Additionally, the model predicts a peak in abundance of mosquitoes old enough to vector malaria at more accurate temperatures than previous models. Our results point to the importance of incorporating detailed vector biology into models for predicting the risk for vector borne diseases.

INSECTICIDAL ACTIVITIES OF ESSENTIAL OILS EXTRACTED FROM THREE SPECIES OF POACEAE ON ANOPHELES GAMBIAE SPP, MAJOR VECTOR OF MALARIA

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Dominique C. K. Sohounhloué

2010-12-01

Full Text Available In this paper, the insecticidal activities on Anopheles gambiae spp of the essential oils (EO extracted from the dry leaves of some species collected in Benin were studied. The essential oil yields are 2.8, 1.7 and 1.4�0respectively for Cymbopogon schoanenthus (L. Spreng (CS, Cymbopogon citratus Stapf. (CC and Cymbopogon giganteus (Hochst. Chiov (CG. The GC/MS analysis showed that the EO of CS had a larger proportion in oxygenated monoterpenes (86.3�20whereas those of the sheets of CC and CG are relatively close proportions (85.5�0and 82.7�0respectively with. The piperitone (68.5�  2-carene (11.5� and -eudesmol (4.6�20are the major components of the EO of CS while trans para-mentha-1(7,8-dien-2-ol (31.9� trans para-mentha-2,8-dien-1-ol (19.6� cis para-mentha-2,8-dien-1-ol (7.2� trans piperitol (6.3�20and limonene (6.3�20prevailed in the EO of CG. The EO of CC revealed a rich composition in geranial (41.3� neral (33� myrcene (10.4� and geraniol (6.6� The biological tests have shown that these three EO induced 100�0mortality of Anopheles gambiae to 1.1, 586.58 and 1549 µg•cm-2 respectively for CC, CS and CG. These effects are also illustrated by weak lethal concentration for 50�0anopheles population (CC: 0.306; CS: 152.453 and CG: 568.327 µg•cm-2 in the same order of reactivity. The EO of CC appeared most active on two stocks (sensitive and resistant of Anopheles gambiae.

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

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Paulo FP Pimenta

2015-02-01

Full Text Available In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

Science.gov (United States)

Pimenta, Paulo FP; Orfano, Alessandra S; Bahia, Ana C; Duarte, Ana PM; Ríos-Velásquez, Claudia M; Melo, Fabrício F; Pessoa, Felipe AC; Oliveira, Giselle A; Campos, Keillen MM; Villegas, Luis Martínez; Rodrigues, Nilton Barnabé; Nacif-Pimenta, Rafael; Simões, Rejane C; Monteiro, Wuelton M; Amino, Rogerio; Traub-Cseko, Yara M; Lima, José BP; Barbosa, Maria GV; Lacerda, Marcus VG; Tadei, Wanderli P; Secundino, Nágila FC

2015-01-01

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence. PMID:25742262

Ultrastructure of a microsporidium brachiola gambiae n.sp.parasitising a mosquito anopheles gamblae, a malaria vector

Czech Academy of Sciences Publication Activity Database

Weiser, Jaroslav; Žižka, Zdeněk

- (2003), s. 35-36 ISSN 1214-021X. [Conference on Cell Biology /5./. České Budějovice, 08.09.2003-10.09.2003] Institutional research plan: CEZ:AV0Z5020903 Keywords : anopheles gambiae * malaria * vector Subject RIV: EE - Microbiology, Virology

BEBERAPA ASPEK BIONOMIK ANOPHELES SP DI KABUPATEN SUMBA TENGAH, PROVINSI NUSA TENGGARA TIMUR

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Ni Wayan Dewi Adyana

2012-07-01

Full Text Available Research Some Aspects of Anopheles sp Bionomik in Central Sumba Regency, Province of East Nusa Tenggara. Committed in the territory Maradesa Health Center. Data were collected by catching adult mosquitoes by using bait People inside and outside the home, a collection of breaks in the wall and at home, continued with larval surveys in all potential breeding places.  The results showed that the biting behavior tends eksofagik found on An. kochi, An. aconitus and An.barbirostris with bite density peaks in An. aconitus (0.6 persons/hour with a biting peak at 20:00 to 21:00. Behavior tends eksofilik break in An. kochi, An. aconitus, An. tesselatus, An. barbirostris, An. vagus, An.flavirostris, An. maculatus and An. indefinitus with the highest density in An.aconitus (0.9 persons/hour at 1:00 a.m. to 2:00 a.m. Anopheles larvae breeding places found in the small hole in the ground, creek, wetland, non-permanent irrigation, water reservoirs in the vegetable garden, ditches, puddles, swamps, springs, with species that are found as An.kochi, An.aconitus, An. tesselatus, An. barbirostris, An. vagus, An. flavirostris, An. maculatus, An. indefinitus and An. annullaris

Ecology of Anopheles dthali Patton in Bandar Abbas District, Hormozgan Province, Southern Iran

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H Vatandoost

2007-06-01

Full Text Available Ecology of Anopheles dthali was studied in Bandar Abbas County, where there is indigenous malaria. Anopheles dthali plays as a secondary malaria vector in the region. It is active throughout the year in mountainous area with two peaks of activity, whereas in coastal area it has one peak. There is no report of hibernation or aestivation for this species in the re¬gion. Precipitin tests on specimens from different parts showed that 15.6-20.8% were positive for human blood. This species usually rests outdoors. It has different larval habitats. Insecticides susceptibility tests on adult females exhibited susceptibil¬ity to all insecticides recommended by WHO. LT50 for the currently used insecticide, lambda-cyhalothrin, is measured less than one minute. The irritability tests to pyrethroid insecticides, showed that permethrin and lambda-cyhalothrin had more irritancy compared to deltamethrin and cyfluthrin. Larval bioassay using malathion, chlorpyrifos, temephos and fenithrothion did not show any sing of resistance to these larvicides at the diagnostic dose. It is recommended that all the decision makers should consider the results of our study for any vector control measures in the region.

Ecology of Anopheles dthali Patton in Bandar Abbas District, Hormozgan Province, Southern Iran

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H Vatandoost

2007-05-01

Full Text Available Ecology of Anopheles dthali was studied in Bandar Abbas County, where there is indigenous malaria. Anopheles dthali plays as a secondary malaria vector in the region. It is active throughout the year in mountainous area with two peaks of activity, whereas in coastal area it has one peak. There is no report of hibernation or aestivation for this species in the re¬gion. Precipitin tests on specimens from different parts showed that 15.6-20.8% were positive for human blood. This species usually rests outdoors. It has different larval habitats. Insecticides susceptibility tests on adult females exhibited susceptibil¬ity to all insecticides recommended by WHO. LT50 for the currently used insecticide, lambda-cyhalothrin, is measured less than one minute. The irritability tests to pyrethroid insecticides, showed that permethrin and lambda-cyhalothrin had more irritancy compared to deltamethrin and cyfluthrin. Larval bioassay using malathion, chlorpyrifos, temephos and fenithrothion did not show any sing of resistance to these larvicides at the diagnostic dose. It is recommended that all the decision makers should consider the results of our study for any vector control measures in the region.

Från outsiderfilmmakare till etablerad indieregissör : David Lynch, Jim Jarmusch och Steven Soderbergh

OpenAIRE

Simberg, Maximilian

2014-01-01

Det här arbetet behandlar kreativ frihet och konstnärligt oberoende i filmskapande, utgående från begreppet independent film och regissörerna David Lynch, Jim Jarmusch och Steven Soderbergh. Den centrala frågeställningen är hur det har varit möjligt för en filmkonstnär att uppnå konstnärligt oberoende och samtidigt ha en långlivad och framgångsrik karriär. Arbetets fokus ligger på de tre regissörernas genombrottsfilmer; Eraserhead, Stranger Than Paradise och sex, lies, and videotape, och förs...

Screening of the DNA mismatch repair genes MLH1, MSH2 and MSH6 in a Greek cohort of Lynch syndrome suspected families

International Nuclear Information System (INIS)

Thodi, Georgia; Fountzilas, George; Yannoukakos, Drakoulis; Fostira, Florentia; Sandaltzopoulos, Raphael; Nasioulas, George; Grivas, Anastasios; Boukovinas, Ioannis; Mylonaki, Maria; Panopoulos, Christos; Magic, Mirjana Brankovic

2010-01-01

Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort. Forty-two samples from twenty-four families, out of which twenty two of Greek, one of Cypriot and one of Serbian origin, were screened for the presence of germline mutations in the major mismatch repair genes through direct sequencing and MLPA. Families were selected upon Amsterdam criteria or revised Bethesda guidelines. Ten deleterious alterations were detected in twelve out of the twenty-four families subjected to genetic testing, thus our detection rate is 50%. Four of the pathogenic point mutations, namely two nonsense, one missense and one splice site change, are novel, whereas the detected genomic deletion encompassing exon 6 of the MLH1 gene has been described repeatedly in the LOVD database. The average age of onset for the development of both colorectal and endometrial cancer among mutation positive families is 43.2 years. The mutational spectrum of the MMR genes investigated as it has been shaped by our analysis is quite heterogeneous without any strong indication for the presence of a founder effect

HNPCC (Lynch Syndrome: Differential Diagnosis, Molecular Genetics and Management - a Review

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Lynch Henry T

2003-12-01

Full Text Available Abstract HNPCC (Lynch syndrome is the most common form of hereditary colorectal cancer (CRC, wherein it accounts for between 2-7 percent of the total CRC burden. When considering the large number of extracolonic cancers integral to the syndrome, namely carcinoma of the endometrium, ovary, stomach, hepatobiliary system, pancreas, small bowel, brain tumors, and upper uroepithelial tract, these estimates of its frequency are likely to be conservative. The diagnosis is based upon its natural history in concert with a comprehensive cancer family history inclusive of all anatomic sites. In order for surveillance and management to be effective and, indeed, lifesaving, among these high-risk patients, the linchpin to cancer control would be the physician, who must be knowledgeable about hereditary cancer syndromes, their molecular and medical genetics, genetic counseling, and, most importantly, the natural history of the disorders, so that the entirety of this knowledge can be melded to highly-targeted management.

Effectiveness of synthetic versus natural human volatiles as attractants for Anopheles gambiae (Diptera: Culicidae) sensu stricto

NARCIS (Netherlands)

Smallegange, R.C.; Knols, B.G.J.; Takken, W.

2010-01-01

Females of the African malaria vector, Anopheles gambiae Giles sensu stricto, use human volatiles to find their blood-host. Previous work has shown that ammonia, lactic acid, and aliphatic carboxylic acids significantly affect host orientation and attraction of this species, In the current study,

HABITAT PERKEMBANGBIAKAN DAN AKTIVITAS MENGGIGIT NYAMUK ANOPHELES SUNDAICUS DAN ANOPHELES SUBPICTUS DI PURWOREJO, JAWA TENGAH

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Supratman Sukowati

2012-11-01

Full Text Available Malaria continues to be a public health problem, it causes morbidity, mortality as well as outbreak in several remote areas in Indonesia. Vector control remains the most effective measure to prevent malaria transmission. The understanding of mosquito species, its bio-ecology, and the characteristic of their habitats are very important to formulate the vector control strategy. It was recognized that there are many aspects of behavior that are directly and indirectly important in the prevention and control of malaria. One of the main cause of malaria control failure due to lack of understanding vector spesies and its bio-ecology.This paper reported the study of breeding places and biting activities of malaria vector Anophles sundaicus and An. subpictus from coastal area of Purworejo area in year 2004. Natural population of anopheline species was sampled from larval survey, landing collection, animal resting collection, resting collection to study the larval habitat, biting activities, resting habit and biting sites. Nine species of anopheline werefound in Jati Malang e.g. An. sundaicus, An. subpictus, An. barbirostris, An. vagus, An. aconitus, An.indefinitus, An. tesselatus, An. nigerrimus, An. annularis. In Gedangan village was found 5 species of Anopheles e.g. An. sundaicus, An. subpictus, An. barbirostris, An. vagus, and An. aconitus.The breeding places of Anopheles spp. are varied, in Jati Malang and Gedangan were found lagoon, brackish water fish-pond, rice field, freshwater fishpond, irrigation channel, and pit hole. Therefore, the breeding places of An. sundaicus and An. subpictus confined in the lagoon and brackish water fish ponds, with its characteristics e.g. water temperature ranges 25,6°C-27,8°C, pH ranges 7,2-7,6, water salinity 3,0-3,4%, and water dept is 20,3 cm-25,2 cm, muddy undergroud, stagnant or slow running water with the water weed mostly green algae (Chlorophyta and lichen.The biting activities of An. sundaicus and An

A novel heterozygous germline deletion in MSH2 gene in a five generation Chinese family with Lynch syndrome

OpenAIRE

Wu, Bin; Ji, Wuyang; Liang, Shengran; Ling, Chao; You, Yan; Xu, Lai; Zhong, Min-Er; Xiao, Yi; Qiu, Hui-Zhong; Lu, Jun-Yang; Banerjee, Santasree

2017-01-01

Lynch syndrome (LS) is one of the most common familial forms of colorectal cancer predisposing syndrome with an autosomal dominant mode of inheritance. LS is caused by the germline mutations in DNA mismatch repair (MMR) genes including MSH2, MLH1, MSH6 and PMS2. Clinically, LS is characterized by high incidence of early-onset colorectal cancer as well as endometrial, small intestinal and urinary tract cancers, usually occur in the third to fourth decade of the life. Here we describe a five ge...

Rare mutations in RINT1 predispose carriers to breast and Lynch Syndrome-spectrum cancers

Science.gov (United States)

Park, Daniel J.; Tao, Kayoko; Le Calvez-Kelm, Florence; Nguyen-Dumont, Tu; Robinot, Nivonirina; Hammet, Fleur; Odefrey, Fabrice; Tsimiklis, Helen; Teo, Zhi L.; Thingholm, Louise B.; Young, Erin L.; Voegele, Catherine; Lonie, Andrew; Pope, Bernard J.; Roane, Terrell C.; Bell, Russell; Hu, Hao; Shankaracharya; Huff, Chad D.; Ellis, Jonathan; Li, Jun; Makunin, Igor V.; John, Esther M.; Andrulis, Irene L.; Terry, Mary B.; Daly, Mary; Buys, Saundra S.; Snyder, Carrie; Lynch, Henry T.; Devilee, Peter; Giles, Graham G.; Hopper, John L.; Feng, Bing J.; Lesueur, Fabienne; Tavtigian, Sean V.; Southey, Melissa C.; Goldgar, David E.

2014-01-01

Approximately half of the familial aggregation of breast cancer remains unexplained. A multiple-case breast cancer family exome sequencing study identified three likely pathogenic mutations in RINT1 (NM_021930.4) not present in public sequencing databases: RINT1 c.343C>T (p.Q115X), c.1132_1134del (p.M378del) and c.1207G>T (p.D403Y). Based on this finding, a population-based case-control mutation-screening study was conducted and identified 29 carriers of rare (MAF Lynch syndrome-spectrum cancers (SIR 3.35, 95% CI 1.7-6.0; P=0.005), particularly for relatives diagnosed with cancer under age 60 years (SIR 10.9, 95%CI 4.7-21; P=0.0003). PMID:25050558

Disecciones de Mosquitos del género Anopheles en la Intendencia del Meta

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Renjifo-Salcedo Santiago

1948-06-01

Full Text Available EI esclarecimiento de los vectores de malaria reviste especial importancia para la salubridad nacional. En la presente comunicación se dan a conocer los resultados de 1048 disecciones de mosquitos del genero Anopheles (889 glándulas y 894 estómagos hechas por nosotros en el Laboratorio de Villavicencio, Instituto "Carlos Finlay", durante los meses de septiembre, octubre, noviembre y diciembre de 1946.

Mitochondrial genome sequences reveal deep divergences among Anopheles punctulatus sibling species in Papua New Guinea

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Logue Kyle

2013-02-01

Full Text Available Abstract Background Members of the Anopheles punctulatus group (AP group are the primary vectors of human malaria in Papua New Guinea. The AP group includes 13 sibling species, most of them morphologically indistinguishable. Understanding why only certain species are able to transmit malaria requires a better comprehension of their evolutionary history. In particular, understanding relationships and divergence times among Anopheles species may enable assessing how malaria-related traits (e.g. blood feeding behaviours, vector competence have evolved. Methods DNA sequences of 14 mitochondrial (mt genomes from five AP sibling species and two species of the Anopheles dirus complex of Southeast Asia were sequenced. DNA sequences from all concatenated protein coding genes (10,770 bp were then analysed using a Bayesian approach to reconstruct phylogenetic relationships and date the divergence of the AP sibling species. Results Phylogenetic reconstruction using the concatenated DNA sequence of all mitochondrial protein coding genes indicates that the ancestors of the AP group arrived in Papua New Guinea 25 to 54 million years ago and rapidly diverged to form the current sibling species. Conclusion Through evaluation of newly described mt genome sequences, this study has revealed a divergence among members of the AP group in Papua New Guinea that would significantly predate the arrival of humans in this region, 50 thousand years ago. The divergence observed among the mtDNA sequences studied here may have resulted from reproductive isolation during historical changes in sea-level through glacial minima and maxima. This leads to a hypothesis that the AP sibling species have evolved independently for potentially thousands of generations. This suggests that the evolution of many phenotypes, such as insecticide resistance will arise independently in each of the AP sibling species studied here.

The Use of Social Media to Recruit Participants With Rare Conditions: Lynch Syndrome as an Example.

Science.gov (United States)

Burton-Chase, Allison M; Parker, Wendy M; Hennig, Kelsey; Sisson, Faith; Bruzzone, Linda L

2017-01-23

Social media is increasingly being used as a means of recruiting participants, particularly for investigators whose areas of interest involve rare conditions or hard-to-reach populations. However, much of the literature to date has focused on paid advertisement recruitment. We used Lynch syndrome (LS), a rare hereditary cancer syndrome, as a model to demonstrate the successful partnership between researchers and a Web-based patient education and advocacy organization to facilitate participant recruitment. Recruitment was undertaken in partnership with Lynch Syndrome International (LSI), an advocacy organization with a strong social media presence. After LSI published our study information, participants followed up via email or phone call. Following prescreening and consent, interested and eligible participants were then sent a secure survey link. Within 36 hours of a single Facebook post by the site administrators for LSI, over 150 individuals responded via phone or email. Sixty-five individuals were sent the survey link and 57 individuals completed the survey (88% response rate). Of note, these 57 individuals were geographically diverse within the Unites States, representing LS patients from 26 different states. This approach has several advantages, including recruitment through a trusted source outside of a clinical setting, higher response rates, and cost-effectiveness with a small research team in a relatively short amount of time. Overall, social media recruitment with a trusted online partner can be highly effective in hard-to-reach clinical populations, such as patients with LS. However, this approach requires additional effort for eligibility screening. ©Allison M Burton-Chase, Wendy M Parker, Kelsey Hennig, Faith Sisson, Linda L Bruzzone. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 23.01.2017.

Biological differences in reproductive strategy between the mosquito sibling species Anopheles gambiae sensu stricto and An. quadriannulatus

NARCIS (Netherlands)

Takken, W.; Stuke, K.; Klowden, M.J.

2002-01-01

Females of the afrotropical mosquito species Anopheles gambiae Giles sensu stricto and An. quadriannulatus (Theobald) (Diptera: Culicidae) were studied for the effect of blood meal size and the frequency of blood feeding on reproductive development during the first gonotrophic cycle. To standardize

Identification of four evolutionarily related G protein-coupled receptors from the malaria mosquito Anopheles gambiae

DEFF Research Database (Denmark)

Belmont, Martin; Cazzamali, Giuseppe; Williamson, Michael

2006-01-01

The mosquito Anopheles gambiae is an important vector for malaria, which is one of the most serious human parasitic diseases in the world, causing up to 2.7 million deaths yearly. To contribute to our understanding of A. gambiae and to the transmission of malaria, we have now cloned four evolutio......The mosquito Anopheles gambiae is an important vector for malaria, which is one of the most serious human parasitic diseases in the world, causing up to 2.7 million deaths yearly. To contribute to our understanding of A. gambiae and to the transmission of malaria, we have now cloned four...... evolutionarily related G protein-coupled receptors (GPCRs) from this mosquito and expressed them in Chinese hamster ovary cells. After screening of a library of thirty-three insect or other invertebrate neuropeptides and eight biogenic amines, we could identify (de-orphanize) three of these GPCRs as...... relationship to the A. gambiae and other insect AKH receptors suggested that it is a receptor for an AKH-like peptide. This is the first published report on evolutionarily related AKH, corazonin, and CCAP receptors in mosquitoes....

The Uterine Sandwich Method for Placenta Previa Accreta in Mullerian Anomaly: Combining the B-Lynch Compression Suture and an Intrauterine Gauze Tampon

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Mustafa Kaplanoğlu

2013-01-01

Full Text Available Mullerian duct anomalies may cause obstetric complications, such as postpartum hemorrhage (PPH and placental adhesion anomalies. Uterine compression suture may be useful for controlling PPH (especially atony. In recent studies, uterine compression sutures have been used in placenta accreta. We report a case of PPH, a placenta accreta accompanying a large septae, treated with B-Lynch suture and intrauterine gauze tampon.

INKRIMINASI VEKTOR MALARIA DAN IDENTIFIKASI PAKAN DARAH PADA NYAMUK AnopHELEs SPP DI KECAMATAN BOROBUDUR, KABUPATEN MAGELANG

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Umi Widyastuti

2013-12-01

Full Text Available AbstrakMalaria masih merupakan masalah kesehatan di Kabupaten Magelang, khususnya di Kecamatan Borobudur. Annual Parasite Incidence (API dua tahun terakhir sebesar 0,19 pada tahun 2004 dan meningkat 0,34 pada tahun 2005, menunjukkan status Low Case Incidence (LCI. Kasus malaria di daerah tersebut sehubungan dengan  adanya  beberapa  spesies  nyamuk  Anopheles  yang  potensial  sebagai  vektor  malaria.  Kompetensi vektorial  nyamuk  Anopheles  di  Kecamatan  Borobudur  belum  banyak  dilaporkan,  khususnya  halam  hal kerentanannya terhadap Plasmodium dan sifat antropofilik (kesukaan menghisap darah manusia. Berbagai spesies seperti Anopheles aconitus, An maculatus, dan An. balabacensis merupakan tersangka vektor malaria di daerah tersebut. Tujuan penelitian ini adalah: a. mendeteksi antigen protein circum sporozoit P. falciparum atau P. vivax pada nyamuk Anopheles sp dengan teknik Enzyme Linked Immunosarbant Assay (Elisa dan b.  mengidentifikasi  pakan  darah  manusia  pada  nyamuk  Anopheles  spp  dengan  teknik  Elisa.  Penelitian dilaksanakan pada bulan Januari-Mei 2006 di 2 desa HCI yaitu di Giripurno dan Giritengah, Kecamatan Borobudur. Penelitian dilakukan dengan menangkap nyamuk yang istirahat di dalam dan luar rumah pada malam hari (18.00-12.00 dan pagi hari (06.00-08.00 sesuai dengan metode WHO, 2003. Nyamuk Anopheles spp dipisahkan berdasarkan spesies untuk dihitung kepadatannya. Selanjutnya dilakukan pembedahan ovarium untuk  mengetahui  paritasnya  (parous  atau  nulliparous. Anopheles  spp  parous  (4  spesies  yaitu Anopheles aconitus, An maculatus, An. balabacensis dan An. barbirostris diperiksa kondisi abdomennya untuk kepentingan pengujian dengan ELISA. Keempat spesies nyamuk parous (semua kondisi abdomen yaitu unfed, blood fed, half gravid dan gravid diambil bagian dada-kepala untuk kepentingan Elisa sporozoit. Nyamuk parous dengan kondisi blood fed dan half gravid diambil bagian

Contributions of Anopheles larval control to malaria suppression in tropical Africa: review of achievements and potential.

Science.gov (United States)

Walker, K; Lynch, M

2007-03-01

Malaria vector control targeting the larval stages of mosquitoes was applied successfully against many species of Anopheles (Diptera: Culicidae) in malarious countries until the mid-20th Century. Since the introduction of DDT in the 1940s and the associated development of indoor residual spraying (IRS), which usually has a more powerful impact than larval control on vectorial capacity, the focus of malaria prevention programmes has shifted to the control of adult vectors. In the Afrotropical Region, where malaria is transmitted mainly by Anopheles funestus Giles and members of the Anopheles gambiae Giles complex, gaps in information on larval ecology and the ability of An. gambiae sensu lato to exploit a wide variety of larval habitats have discouraged efforts to develop and implement larval control strategies. Opportunities to complement adulticiding with other components of integrated vector management, along with concerns about insecticide resistance, environmental impacts, rising costs of IRS and logistical constraints, have stimulated renewed interest in larval control of malaria vectors. Techniques include environmental management, involving the temporary or permanent removal of anopheline larval habitats, as well as larviciding with chemical or biological agents. This present review covers large-scale trials of anopheline larval control methods, focusing on field studies in Africa conducted within the past 15 years. Although such studies are limited in number and scope, their results suggest that targeting larvae, particularly in human-made habitats, can significantly reduce malaria transmission in appropriate settings. These approaches are especially suitable for urban areas, where larval habitats are limited, particularly when applied in conjunction with IRS and other adulticidal measures, such as the use of insecticide treated bednets.

FAUNA ANOPHELES DI DAERAH PANTAI BEKAS HUTAN MANGROVE KECAMATAN PADANG CERMIN KABUPATEN LAMPUNG SELATAN

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N. Sushanti Idris-Idram

2012-09-01

Full Text Available Intensive mosquito collections were carried out in two villages in subdistrict of Padangcermin during 1992-1993. The method of mosquito collections consisted of night landing on man indoor and outdoor, night resting indoor and outdoor around cattle shelters, light trap in cattle shelters, daytime resting indoor and outdoor, as well as larvae collections to identify anophelines breeding sites. Sixteen anophelines i.e. Anopheles sundaicus, An. subpictus, An. vagus, An. indefinitus, An. nigerrimus, An. peditaeniatus, An. kochi, An. barbirostris, An. bambumbrosus, An. annularis, An. separatus, An. tesselatus, An. aconitus, An. umbrosus, An. leucosphyrus and An. letifer were collected. Among these mosquitos, An. sundaicus was found predominant, followed by An. vagus and An. subpictus. Other species were collected in small numbers. The behavior of Anopheles sundaicus, An. subpictus and An. vagus were exophagic and endophilic. The larvae of An. sundaicus was found only in brackish standing water such as abandoned shrimp ponds, An. subpictus in brackish standing water as well as fresh standing water, while An. vagus was found only in fresh standing water. Breeding sites of An. sundaicus was characterized by pond with floating algae while An. subpictus and An. vagus were not depending on vegetation.

A(maize)ing attraction: gravid Anopheles arabiensis are attracted and oviposit in response to maize pollen odours.

Science.gov (United States)

Wondwosen, Betelehem; Hill, Sharon R; Birgersson, Göran; Seyoum, Emiru; Tekie, Habte; Ignell, Rickard

2017-01-23

Maize cultivation contributes to the prevalence of malaria mosquitoes and exacerbates malaria transmission in sub-Saharan Africa. The pollen from maize serves as an important larval food source for Anopheles mosquitoes, and females that are able to detect breeding sites where maize pollen is abundant may provide their offspring with selective advantages. Anopheles mosquitoes are hypothesized to locate, discriminate among, and select such sites using olfactory cues, and that synthetic volatile blends can mimic these olfactory-guided behaviours. Two-port olfactometer and two-choice oviposition assays were used to assess the attraction and oviposition preference of gravid Anopheles arabiensis to the headspace of the pollen from two maize cultivars (BH-660 and ZM-521). Bioactive compounds were identified using combined gas chromatography and electroantennographic detection from the headspace of the cultivar found to be most attractive (BH-660). Synthetic blends of the volatile compounds were then assessed for attraction and oviposition preference of gravid An. arabiensis, as above. Here the collected headspace volatiles from the pollen of two maize cultivars was shown to differentially attract and stimulate oviposition in gravid An. arabiensis. Furthermore, a five-component synthetic maize pollen odour blend was identified, which elicited the full oviposition behavioural repertoire of the gravid mosquitoes. The cues identified from maize pollen provide important substrates for the development of novel control measures that modulate gravid female behaviour. Such measures are irrespective of indoor or outdoor feeding and resting patterns, thus providing a much-needed addition to the arsenal of tools that currently target indoor biting mosquitoes.

BIONOMIK NYAMUK Anopheles DAN KEBIASAAN PENDUDUK YANG MENUNJANG KEJADIAN MALARIA DI KECAMATAN PAGEDONGAN KABUPATEN BANJARNEGARA TAHUN 2005

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Jarohman Raharjo

2013-03-01

Full Text Available Malaria masih merupakan masalah kesehatan global termasuk di Indonesia. Kabupaten Banjarnegara merupakan salah satu kabupaten di Jawa Tengah yang mempunyai masalah malaria cukup serius. Sampai dengan tahun 2002 telah tercatat 86 desa endemis dari 276 desa yang ada, sedangkan 175 desa terancam menjadi daerah HCI (High Case lncidens, jumlah penderita malaria pada tahun 2001 sebanyak 6.793 orang (API: 7,47%o meningkat menjadi 13.401 orang (API: 15,33%o pada tahun 2002 dan 90,2% dari kasus penderita indigenous.Tujuan penelitian ini adalah mengetahui bionomik nyamuk anopheles dan kebiasaan penduduk yang menunjang kejadian malaria di lokasi penelitian.Penelitian ini termasuk dalam jenis penelitian deskriptif, karena menggambarkan bionomik nyamuk vektor dan kebiasaan penduduk. Penelitian ini bertempat di Kecamatan Pagedongan, KabupatenBanjarnegara, Provinsi Jawa Tengah dilaksanakan pada bulan Februari Nopember 2005.Tempat berkembangbiak Anopheles spp positif adalah kobakan air (belik dan bekas galian pasir disungai dan mata air. Kebiasaan nyamuk Anopheles spp menggigit orang di dalam dan di luar rumah hampir sama banyaknya. Terjadi peningkatan jumlah nyamuk yang tajam pada bulan September. Aktivitas menggigit di dalam rumah dimulai pada pukul 18.00-19.00. Sedangkan aktivitas menggigit di luar rumah meningkat pada pukul 21. 00-22.00 dan mencapai puncaknya pada pukul 22. 00-23.00 dan 03.00-04.00.Kesimpulan dari penelitian ini adalah adanya nyamuk tersangka vektor, kondisi lingkungan dan pengetahuan masyarakat menjadi faktor yang menunjang kejadian malaria di desa wilayah Kecamatan Pagedongan. Saran yang diberikan adalah meningkatkan pengetahuan masyarakat tentang malaria dan mengurangi keberadaan tempat-tempat perkembangbiakan nyamuk. Kata Kunci : Malaria, Biomonik

La representación de los personajes monstruosos en el cine de David Lynch: Cabeza Borradora y El Hombre Elefante

OpenAIRE

Suñer Royo, Iris

2015-01-01

Treball final de Grau en Comunicació Audiovisual. Codi: CA0932. Curs acadèmic 2014-2015 El universo creado por David Lynch es prácticamente inabarcable, sin embargo, con cada producto que realiza incorpora nuevas estrategias expresivas y formales que podemos desglosar y analizar para entender cada vez mejor como su mente y creatividad se desarrollan. Para ello hemos empezado desde el principio, por sus dos primeros largometrajes, los cuales son los únicos filmados en blanco ...

Implications for changes in Anopheles darlingi biting behaviour in three communities in the peri-Iquitos region of Amazonian Peru.

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Moreno, Marta; Saavedra, Marlon P; Bickersmith, Sara A; Lainhart, William; Tong, Carlos; Alava, Freddy; Vinetz, Joseph M; Conn, Jan E

2015-07-30

Malaria transmission in the peri-Iquitos region of Amazonian Peru has been designated as seasonal and hypo-endemic with recently described hyper-endemic hotspots. Despite relatively recent distribution of long-lasting insecticidal bed nets (LLINs), malaria in Amazonian Peru persists and increased substantially in 2014 compared to previous years. Anopheles darlingi, identified as the main malaria vector, is known for its variable behaviour depending on locality and environment. To evaluate vector biology metrics in relation to seasonality and malaria transmission, mosquito collections were carried out in three localities in the peri-Iquitos region, Loreto, Peru in 2011-2012. Human landing catch (HLC) collection method, Shannon (SHA) and CDC trap types were compared for effectiveness in a neotropical setting. Abundance, human biting rate and entomological inoculation rate (EIR) were measured to provide an updated view of transmission patterns post-LLIN distribution. HLC collected significantly more anopheline mosquitoes than SHA and CDC light traps. Anopheles darlingi was the most prevalent species in all three villages (84% overall). Biting patterns varied depending on trap type, season and village. EIR varied temporally (monthly) and spatially and the highest (2.52) occurred during the 2012 malaria outbreak in Cahuide. Unexpectedly there was a high infection rate (1.47 and 1.75) outside the normal malaria transmission season, coincident with a second local outbreak in Cahuide. The first identification of Anopheles dunhami and Anopheles oswaldoi C in Peru, using molecular markers, is also reported in this study. These data underscore the importance of HLC as the most meaningful collection method for measuring vector biology indices in this region. The highest monthly EIR provides additional evidence of seasonal transmission in riverine localities correlated with high river levels, and An. darlingi as the only contributor to transmission. The trend of an increase in

[Identification of anopheles breeding sites in the residual foci of low malaria transmission «hotspots» in Central and Western Senegal].

Science.gov (United States)

Sy, O; Konaté, L; Ndiaye, A; Dia, I; Diallo, A; Taïrou, F; Bâ, E L; Gomis, J F; Ndiaye, J L; Cissé, B; Gaye, O; Faye, O

2016-02-01

Malaria incidence has markedly declined in the Mbour, Fatick, Niakhar and Bambey districts (central and western Senegal) thanks to a scaling up of effective control measures namely LLINs (Long Lasting Insecticide Treated Net), ACTs (Artesunate Combination Therapy) and promoting care seeking. However malaria cases are now maintained by foci of transmission called hotspots. We evaluate the role of anopheles breeding sites in the identification of malaria hotspots in the health districts of Mbour, Fatick, Niakhar and Bambey. Surveys of breeding sites were made in 6 hotspot villages and 4 non-hotspot villages. A sample was taken in each water point with mosquito larvae by dipping method and the collected specimens were identified to the genus level. Additional parameters as name of the village and breeding sites, type of collection, original water turbidity, presence of vegetation, proximity to dwellings, geographic coordinates, sizes were also collected. Sixty-two water collections were surveyed and monitored between 2013 and 2014. Temporary natural breeding sites were predominant regardless of the epidemiological status of the village. Among the 31 breeding sites located within 500 meters of dwellings in hotspots villages, 70% carried Anopheles larvae during the rainy season while 43% of the 21 breeding sites located at similar distances in non-hotspot villages carried Anopheles larvae during the same period (P = 0.042). At the end of the rainy season, the trend is the same with 27% of positive breeding sites in hotspots and 14% in non-hotspots villages. The breeding sites encountered in hotspots villages are mostly small to medium size and are more productive by Anopheles larvae than those found in non-hotspot area. This study showed that the high frequency of smallest and productive breeding sites around and inside the villages can create conditions of residual transmission.

The Brazilian Malaria Vector Anopheles (Kerteszia) Cruzii: Life Stages and Biology (Diptera: Culicidae)

Science.gov (United States)

1991-11-01

Mosquitos no litoral paranaense. I - Idade fisioldgica de no Parque National da Serra dos Orgaos, Anopheles cruzii (Diptera, Culicidae). Arq. Estado do...no Parque National da Peryassii, A.G. 1908. OS culicideos do Brazil. Serra dos Grgaos, Estado do Rio de Janeiro, Inst. de Manguinhos, Rio de Janeiro...Kerteszia no litoral Guimar%es, A.E. and V.N.M. Victoria. 1986. do estado de Santa Catarina. Rev. Bras. Mosquitos no Parque National da Serra dos

The efficacy of repellents against Aedes, Anopheles, Culex and Ixodes spp. - a literature review.

Science.gov (United States)

Lupi, Eleonora; Hatz, Christoph; Schlagenhauf, Patricia

2013-01-01

Travellers are confronted with a variety of vector-borne threats. Is one type of repellent effective against all biting vectors? The aim of this review is to examine the literature, up to December 31st, 2012, regarding repellent efficacy. We searched PubMed for relevant papers. Repellents of interest were DEET, Icaridin as well as other piperidine-derived products (SS220), Insect Repellent (IR) 3535 (ethyl-butylacetyl-amino-propionat, EBAAP) and plant-derived products, including Citriodora (para-menthane-3,8-diol). As vectors, we considered the mosquito species Anopheles, Aedes and Culex as well as the tick species Ixodes. We selected only studies evaluating the protective efficacy of repellents on human skin. We reviewed a total of 102 publications. Repellents were evaluated regarding complete protection time or as percentage efficacy [%] in a time interval. We found no standardized study for tick bite prevention. Regarding Aedes, DEET at concentration of 20% or more, showed the best efficacy providing up to 10 h protection. Citriodora repellency against this mosquito genus was lower compared to the other products. Also between subspecies a difference could be observed: Ae. aegypti proved more difficult to repel than Ae. Albopictus. Fewer studies have been conducted on mosquito species Anopheles and Culex. The repellency profile against Anopheles species was similar for the four principal repellents of interest, providing on average 4-10 h of protection. Culex mosquitoes are easier to repel and all four repellents provided good protection. Few studies have been conducted on the tick species Ixodes. According to our results, the longest protection against Ixodes scapularis was provided by repellents containing IR3535, while DEET and commercial products containing Icaridin or PMD showed a better response than IR3535 against Ixodes ricinus. Many plant-based repellents provide only short duration protection. Adding vanillin 5% to plant-based repellents and to DEET

Development of a gravid trap for collecting live malaria vectors Anopheles gambiae s.l.

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Sisay Dugassa

Full Text Available Effective malaria vector control targeting indoor host-seeking mosquitoes has resulted in fewer vectors entering houses in many areas of sub-Saharan Africa, with the proportion of vectors outdoors becoming more important in the transmission of this disease. This study aimed to develop a gravid trap for the outdoor collection of the malaria vector Anopheles gambiae s.l. based on evaluation and modification of commercially available gravid traps.Experiments were implemented in an 80 m(2 semi-field system where 200 gravid Anopheles gambiae s.s. were released nightly. The efficacy of the Box, CDC and Frommer updraft gravid traps was compared. The Box gravid trap was tested to determine if the presence of the trap over water and the trap's sound affected catch size. Mosquitoes approaching the treatment were evaluated using electrocuting nets or detergents added to the water in the trap. Based on the results, a new gravid trap (OviART trap that provided an open, unobstructed oviposition site was developed and evaluated.Box and CDC gravid traps collected similar numbers (relative rate (RR 0.8, 95% confidence interval (CI 0.6-1.2; p = 0.284, whereas the Frommer trap caught 70% fewer mosquitoes (RR 0.3, 95% CI 0.2-0.5; p < 0.001. The number of mosquitoes approaching the Box trap was significantly reduced when the trap was positioned over a water-filled basin compared to an open pond (RR 0.7 95% CI 0.6-0.7; p < 0.001. This effect was not due to the sound of the trap. Catch size increased by 60% (RR 1.6, 1.2-2.2; p = 0.001 with the new OviART trap.Gravid An. Gambiae s.s. females were visually deterred by the presence of the trapping device directly over the oviposition medium. Based on these investigations, an effective gravid trap was developed that provides open landing space for egg-laying Anopheles.

Beberapa aspek perilaku Anopheles sundaicus di Desa Konda Maloba Kecamatan Katikutana Selatan Kabupaten Sumba Tengah

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Ira Indriaty Paskalita Bule Sopi

2015-01-01

Full Text Available Abstract. Konda Maloba village is one of the areas of malaria risk is high enough. Research surveys conducted in the region with cross sectional data collection. The purpose of this paper is to investigate behavioral aspect of Anopheles sundaicus in Konda Maloba Village, Katikutana District, Central Sumba Regency includes breeding sites, density, characteristics of the environment, bitting and resting activity. Data collection was conducted by human-bait collection method and resting, the detention pra-matured mosquitos and propagation mullet observation. The result showed that the characteristics of breeding habitats of Anopheles sundaicus found in water flow with density 4.1, temperature 25ºC, pH 8.8, salinity 12%, cloudy, heliophilik and biota Cambarus virilis, Poa Annua, and Sphagnum sp. Of 681 An. sundaicus was captured through outdoor landing collection (30.90%, indoor landing collection (30.40%, resting on the wall (23.20% and in the cage (15.95%. Indoor bitting activity of An. sundaicus reached a peak in November (MBR=7,21. The highest indoor man-hour density was experienced in November (MHD=0,78 during 01.00-02.00 a.m. The environmental characteristics and An. sundaicus behavior were potentially maintained malaria transmission in Konda Maloba village, South Katikutana. Keywords: behavior, vector, malaria, Anopheles sundaicus Abstrak. Desa Konda Maloba merupakan salah satu wilayah risiko malaria cukup tinggi. Penelitian survey dilakukan di wilayah tersebut dengan pengumpulan data secara cross-sectional. Tujuan penelitian untuk mengetahui gambaran beberapa aspek perilaku An .sundaicus meliputi jenis habitat perkembangbiakan, kepadatan, karakteristik lingkungannya, aktifitas menghisap darah dan istirahat. Pengumpulan data melalui metode koleksi umpan badan orang dan istirahat, pencidukan nyamuk pradewasa dan observasi habitat perkembangbiakan. Hasil penelitian menunjukkan bahwa karakteristik habitat perkembangbiakan An.sundaicus pada

IgG responses to Anopheles gambiae salivary antigen gSG6 detect variation in exposure to malaria vectors and disease risk

DEFF Research Database (Denmark)

Stone, Will; Bousema, Teun; Jones, Sophie

2012-01-01

as the basis of an immuno-assay determining exposure to Afrotropical malaria vectors. In the present study, IgG responses to gSG6 and 6 malaria antigens (CSP, AMA-1, MSP-1, MSP-3, GLURP R1, and GLURP R2) were compared to Anopheles exposure and malaria incidence in a cohort of children from Korogwe district...... with subsequent malaria incidence (test for trend p¿=¿0.004), comparable to malaria antigens MSP-1 and GLURP R2. Our results show that the gSG6 assay is sensitive to micro-epidemiological variations in exposure to Anopheles mosquitoes, and provides a correlate of malaria risk that is unrelated to immune...

The role of skin microbiota in the attractiveness of humans to the malaria mosquito Anopheles gambiae Giles

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Verhulst, N.O.

2010-01-01

Malaria is one of the most serious infectious diseases in the world. The African mosquito Anopheles gambiae sensu stricto (henceforth termed An. gambiae) is highly competent for malaria parasites and preferably feeds on humans inside houses, which make it one of the most effective vectors of the

Carbon dioxide baited trap catches do not correlate with human landing collections of Anopheles aquasalis in Suriname

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Hiwat-van Laar, H.; Andriessen, R.; Rijk, de M.; Koenraadt, C.J.M.; Takken, W.

2011-01-01

Three types of carbon dioxide-baited traps, i.e., the Centers for Disease Control Miniature Light Trap without light, the BioGents (BG) Sentinel Mosquito Trap (BG-Sentinel) and the Mosquito Magnet® Liberty Plus were compared with human landing collections in their efficiency in collecting Anopheles

Human skin microbiota and their volatiles as odour baits for the malaria mosquito Anopheles gambiae s.s

NARCIS (Netherlands)

Verhulst, N.O.; Mukabana, W.R.; Takken, W.; Smallegange, R.C.

2011-01-01

Host seeking by the malaria mosquito Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) is mainly guided by volatile chemicals present in human odours. The skin microbiota plays an important role in the production of these volatiles, and skin bacteria grown on agar plates attract An. gambiae

Uncertainties in the Management of a Lynch Syndrome Patient: A Case Report

Science.gov (United States)

Campos, Sara; Amaro, Pedro; Cunha, Inês; Fraga, João; Cipriano, Maria Augusta; Tomé, Luís

2017-01-01

Introduction Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is characterized by mutations in mismatch repair (MMR) genes leading to an increased cancer risk, namely colorectal cancer. Case In the context of surveillance colonoscopy, a 40-mm flat lesion (0-IIa+b, Paris classification) was identified and submitted to piecemeal mucosal endoscopic resection in a 64-year-old LS patient with an MLH1 germline mutation (262delATC) and two previous segmental resections due to metachronous colorectal cancer. Pathology raised the suspicion of superficial submucosal invasive carcinoma with poor differentiation. Immunochemistry showed heterogeneous MLH1 expression and PMS2 loss. In a short-term follow-up colonoscopy, another 30-mm advanced carcinoma was identified. The patient was referred to surgery. Conclusion This case raises several issues: (1) the potentially fast tumorigenesis and progression to carcinoma in LS and implications for endoscopic screening and surveillance; (2) pitfalls in the interpretation of MMR proteins immunochemistry; (3) the role of endoscopic resection in LS. PMID:29255760

Uncertainties in the Management of a Lynch Syndrome Patient: A Case Report

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Sara Campos

2017-03-01

Full Text Available Introduction: Lynch syndrome (LS, the most common hereditary colorectal cancer syndrome, is characterized by mutations in mismatch repair (MMR genes leading to an increased cancer risk, namely colorectal cancer. Case: In the context of surveillance colonoscopy, a 40-mm flat lesion (0-IIa+b, Paris classification was identified and submitted to piecemeal mucosal endoscopic resection in a 64-year-old LS patient with an MLH1 germline mutation (262delATC and two previous segmental resections due to metachronous colorectal cancer. Pathology raised the suspicion of superficial submucosal invasive carcinoma with poor differentiation. Immunochemistry showed heterogeneous MLH1 expression and PMS2 loss. In a short-term follow-up colonoscopy, another 30-mm advanced carcinoma was identified. The patient was referred to surgery. Conclusion: This case raises several issues: (1 the potentially fast tumorigenesis and progression to carcinoma in LS and implications for endoscopic screening and surveillance; (2 pitfalls in the interpretation of MMR proteins immunochemistry; (3 the role of endoscopic resection in LS.