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Sample records for resembling human sporadic

  1. A molecular model for sporadic human aneuploidy.

    PubMed

    Warren, William D; Gorringe, Kylie L

    2006-04-01

    Aneuploidy is a leading cause of birth defects and a significant contributor to infertility in humans. Maternal age is the only well-established risk factor for gametic aneuploidy in the general population, with the underlying cause(s) yet to be identified. Here we present an extension of the 'two-hit' model for sporadic human aneuploidy. An important implication of this model is that the genetic makeup of an individual will influence the threshold where recombinationally at-risk oocytes (hit-1 events) become sensitive to the effects of advancing age (hit-2 events). Consequently, the age-related risk of gametic aneuploidy in many individuals is likely to differ significantly from the population average, and single nucleotide polymorphisms (SNPs) associated with altered risk should be identifiable.

  2. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda

    PubMed Central

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT. PMID:27293254

  3. Differentiated human stem cells resemble fetal, not adult, β cells.

    PubMed

    Hrvatin, Sinisa; O'Donnell, Charles W; Deng, Francis; Millman, Jeffrey R; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K; Melton, Douglas A

    2014-02-25

    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS(+)) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS(+) cells and (ii) hPSC-derived INS(+) (hPSC-INS(+)) cells more closely resemble human fetal β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS(+) cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS(+) cells into functional β cells.

  4. Muscular dystrophy in a dog resembling human becker muscular dystrophy.

    PubMed

    Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

    2014-05-01

    A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man.

  5. Feline epidermal nevi resembling human inflammatory linear verrucous epidermal nevus.

    PubMed

    Sato, Masafumi; Kariya, Kazuhiro; Matsumoto, Munetaka; Itoh, Miyuki; Kobayashi, Yoshiyasu; Nishifuji, Koji; Kamiie, Junichi; Shirota, Kinji

    2012-10-01

    Multiple, pigmented, verrucous, cutaneous lesions in a 2-year-old female cat were pathologically examined. The lesions were linearly arranged on the right side of the body, and had developed along with moderate pruritus since infancy. Histologically, prominent exophytic, papillomatous outgrowths of the epidermis and acanthosis with intense ortho and parakeratotic hyperkeratosis were characteristic of the lesions. Dermal inflammation with mononuclear cells, neutrophils, and eosinophils was also noted. Inclusion bodies, cellular degeneration, and intranuclear viral particles suggesting papillomavirus infection in the keratinocytes were not observed. Papillomavirus antigen and DNA were not detected in the lesions by immunohistochemistry and polymerase chain reaction, respectively. In accordance with these clinical and histopathological features, the cutaneous lesions of the present cat were diagnosed as epidermal nevi, which were consistent with human inflammatory linear verrucous epidermal nevi.

  6. A Drosophila gene encoding a protein resembling the human. beta. -amyloid protein precursor

    SciTech Connect

    Rosen, D.R.; Martin-Morris, L.; Luo, L.; White, K. )

    1989-04-01

    The authors have isolated genomic and cDNA clones for a Drosophila gene resembling the human {beta}-amyloid precursor protein (APP). This gene produces a nervous system-enriched 6.5-kilobase transcript. Sequencing of cDNAs derived from the 6.5-kilobase transcript predicts an 886-amino acid polypeptide. This polypeptide contains a putative transmembrane domain and exhibits strong sequence similarity to cytoplasmic and extracellular regions of the human {beta}-amyloid precursor protein. There is a high probability that this Drosophila gene corresponds to the essential Drosophila locus vnd, a gene required for embryonic nervous system development.

  7. A Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor.

    PubMed Central

    Rosen, D R; Martin-Morris, L; Luo, L Q; White, K

    1989-01-01

    We have isolated genomic and cDNA clones for a Drosophila gene resembling the human beta-amyloid precursor protein (APP). This gene produces a nervous system-enriched 6.5-kilobase transcript. Sequencing of cDNAs derived from the 6.5-kilobase transcript predicts an 886-amino acid polypeptide. This polypeptide contains a putative transmembrane domain and exhibits strong sequence similarity to cytoplasmic and extracellular regions of the human beta-amyloid precursor protein. There is a high probability that this Drosophila gene corresponds to the essential Drosophila locus vnd, a gene required for embryonic nervous system development. Images PMID:2494667

  8. American alligator proximal pedal phalanges resemble human finger bones: Diagnostic criteria for forensic investigators.

    PubMed

    Ferraro, Joseph V; Binetti, Katie M

    2014-07-01

    A scientific approach to bone and tooth identification requires analysts to pursue the goal of empirical falsification. That is, they may attribute a questioned specimen to element and taxon only after having ruled out all other possible attributions. This requires analysts to possess a thorough understanding of both human and non-human osteology, particularly so for remains that may be morphologically similar across taxa. To date, forensic anthropologists have identified several potential 'mimics' for human skeletal remains, including pig teeth and bear paws. Here we document another possible mimic for isolated human skeletal elements--the proximal pedal phalanges of American alligators (Alligator mississippiensis) closely resemble the proximal and intermediate hand phalanges of adult humans. We detail morphological similarities and differences between these elements, with the goal of providing sufficient information for investigators to confidently falsify the hypothesis that a questioned phalanx is derived from an American alligator.

  9. Sclerosing cholangitis in baboons (Papio spp) resembling primary sclerosing cholangitis of humans.

    PubMed

    Arenas-Gamboa, A M; Bearss, J J; Hubbard, G B; Porter, B F; Owston, M A; Dick, E J

    2012-05-01

    Primary sclerosing cholangitis is a chronic and progressive cholestatic liver disease that has been extensively documented in the human literature. Although it shares many features in common with chronic lymphocytic cholangitis in cats, primary sclerosing cholangitis has never been reported in a nonhuman primate. Primary sclerosing cholangitis is characterized by the presence of intrahepatic and/or extrahepatic inflammation and concentric fibrosis of bile ducts, eventually leading to cirrhosis and hepatic failure. The pathogenesis and cause remain unknown, but the disease likely involves a multifactorial mechanism with genetic- and immune-mediated components. The authors report 2 cases that histologically resemble the condition in humans; they consist of 2 adult male baboons with a clinical history of chronic elevated liver enzymes. In both cases, the liver was histologically characterized by thick bands of fibrosis and mild lymphoplasmacytic periportal cholangiohepatitis with concentric periductal fibrosis, resulting in atrophy and loss of bile ducts. Immunohistochemical analysis revealed positivity of hepatocytes to cytokeratin 7. Masson stain demonstrated marked biliary fibrosis. This is the first report that resembles sclerosing cholangitis in a nonhuman primate, and it suggests that the baboon may provide a useful animal model for this condition in humans.

  10. A Mouse Model of Diet-Induced Obesity Resembling Most Features of Human Metabolic Syndrome

    PubMed Central

    Della Vedova, Maria C.; Muñoz, Marcos D.; Santillan, Lucas D.; Plateo-Pignatari, Maria G.; Germanó, Maria J.; Rinaldi Tosi, Martín E.; Garcia, Silvina; Gomez, Nidia N.; Fornes, Miguel W.; Gomez Mejiba, Sandra E.; Ramirez, Dario C.

    2016-01-01

    Increased chicken-derived fat and fructose consumption in the human diet is paralleled by an increasing prevalence of obesity and metabolic syndrome (MS). Herein, we aimed at developing and characterizing a mouse model of diet-induced obesity (DIO) resembling most of the key features of the human MS. To accomplish this, we fed male C57BL/6J mice for 4, 8, 12, and 16 weeks with either a low-fat diet (LFD) or a high-chicken-fat diet (HFD) and tap water with or without 10% fructose (F). This experimental design resulted in the following four experimental groups: LFD, LFD + F, HFD, and HFD + F. Over the feeding period, and on a weekly basis, the HFD + F group had more caloric intake and gained more weight than the other experimental groups. Compared to the other groups, and at the end of the feeding period, the HFD + F group had a higher adipogenic index, total cholesterol, low-density lipoprotein cholesterol, fasting basal glycemia, insulin resistance, hypertension, and atherogenic index and showed steatohepatitis and systemic oxidative stress/inflammation. A mouse model of DIO that will allow us to study the effect of MS in different organs and systems has been developed and characterized. PMID:27980421

  11. Human endomembrane H sup + pump strongly resembles the ATP-synthetase of Archaebacteria

    SciTech Connect

    Suedhof, T.C.; Stone, D.K.; Johnston, P.A.; Xie, Xiaosong ); Fried, V.A. )

    1989-08-01

    Preparations of mammalian H{sup +} pumps that acidify intracellular vesicles contain eight or nine polypeptides, ranging in size from 116 to 17 kDa. Biochemical analysis indicates that the 70- and 58-kDa polypeptides are subunits critical for ATP hydrolysis. The amino acid sequences of the major catalytic subunits (58 and 70 kDa) of the endomembrane H{sup +} pump are unknown from animal cells. The authors report here the complete sequence of the 58-kDa subunit derived from a human kidney cDNA clone and partial sequences of the 70- and 58-kDa subunits purified from clathrin-coated vesicles of bovine brain. The amino acid sequences of both proteins strongly resemble the sequences of the corresponding subunits of the vacuolar H{sup +} pumps of Archaebacteria, plants, and fungi. The archaebacterial enzyme is believed to use a H{sup +} gradient to synthesize ATP. Thus, a common ancestral protein has given rise to a H{sup +} pump that synthesizes ATP in one organism and hydrolyzes it in another and is highly conserved from prokaryotes to humans. The same pump appears to mediate the acidification of intracellular organelles, including coated vesicles, lysosomes, and secretory granules, as well as extracellular fluids such as urine.

  12. Response of mice to continuous 5-day passive hyperthermia resembles human heat acclimation.

    PubMed

    Sareh, Houtan; Tulapurkar, Mohan E; Shah, Nirav G; Singh, Ishwar S; Hasday, Jeffrey D

    2011-05-01

    Chronic repeated exposure to hyperthermia in humans results in heat acclimation (HA), an adaptive process that is attained in humans by repeated exposure to hyperthermia and is characterized by improved heat elimination and increased exercise capacity, and acquired thermal tolerance (ATT), a cellular response characterized by increased baseline heat shock protein (HSP) expression and blunting of the acute increase in HSP expression stimulated by re-exposure to thermal stress. Epidemiologic studies in military personnel operating in hot environments and elite athletes suggest that repeated exposure to hyperthermia may also exert long-term health effects. Animal models demonstrate that coincident exposure to mild hyperthermia or prior exposure to severe hyperthermia can profoundly affect the course of experimental infection and injury, but these models do not represent HA. In this study, we demonstrate that CD-1 mice continuously exposed to mild hyperthermia (ambient temperature ~37°C causing ~2°C increase in core temperature) for 5 days and then exposed to a thermal stress (42°C ambient temperature for 40 min) exhibited some of the salient features of human HA, including (1) slower warming during thermal stress and more rapid cooling during recovery and (2) increased activity during thermal stress, as well as some of the features of ATT, including (1) increased baseline expression of HSP72 and HSP90 in lung, heart, spleen, liver, and brain; and (2) blunted incremental increase in HSP72 expression following acute thermal stress. This study suggests that continuous 5-day exposure of CD-1 mice to mild hyperthermia induces a state that resembles the physiologic and cellular responses of human HA. This model may be useful for analyzing the molecular mechanisms of HA and its consequences on host responsiveness to subsequent stresses.

  13. Mutations in human lymphocytes commonly involve gene duplication and resemble those seen in cancer cells

    SciTech Connect

    Turner, D.R.; Grist, S.A.; Janatipour, M.; Morley, A.A.

    1988-05-01

    Mutations in human lymphocytes are commonly due to gene deletion. To investigate the mechanism of deletion for autosomal genes, the authors immunoselected lymphocytes mutated at the HLA-A locus and clones them for molecular analysis. Of 36 mutant clones that showed deletion of the selected HLA-A allele, 8 had resulted from a simple gene deletion, whereas 28 had resulted from a more complex mutational event involving reduplication of the nonselected HLA-A allele as indicated by hybridization intensity on Southern blots. In 3 of the 28 clones, retention of heterozygosity at the HLA-B locus indicated that the reduplication was due to recombination between the two chromosomes 6; but in the remaining 25 clones, distinction could not be made between recombination and chromosome reduplication. The results indicate that mutations in normal somatic cells frequently result in hemizygosity or homozygosity at gene loci and, thereby, resemble the mutations thought to be important in the etiology of various forms of cancer.

  14. Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.

    PubMed

    Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

    2014-01-01

    Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model.

  15. Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma

    PubMed Central

    Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

    2014-01-01

    Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. PMID:24128326

  16. Somatic activating mutations in Pik3ca cause sporadic venous malformations in mice and humans.

    PubMed

    Castillo, Sandra D; Tzouanacou, Elena; Zaw-Thin, May; Berenjeno, Inma M; Parker, Victoria E R; Chivite, Iñigo; Milà-Guasch, Maria; Pearce, Wayne; Solomon, Isabelle; Angulo-Urarte, Ana; Figueiredo, Ana M; Dewhurst, Robert E; Knox, Rachel G; Clark, Graeme R; Scudamore, Cheryl L; Badar, Adam; Kalber, Tammy L; Foster, Julie; Stuckey, Daniel J; David, Anna L; Phillips, Wayne A; Lythgoe, Mark F; Wilson, Valerie; Semple, Robert K; Sebire, Neil J; Kinsler, Veronica A; Graupera, Mariona; Vanhaesebroeck, Bart

    2016-03-30

    Venous malformations (VMs) are painful and deforming vascular lesions composed of dilated vascular channels, which are present from birth. Mutations in the TEK gene, encoding the tyrosine kinase receptor TIE2, are found in about half of sporadic (nonfamilial) VMs, and the causes of the remaining cases are unknown. Sclerotherapy, widely accepted as first-line treatment, is not fully efficient, and targeted therapy for this disease remains underexplored. We have generated a mouse model that faithfully mirrors human VM through mosaic expression of Pik3ca(H1047R), a constitutively active mutant of the p110α isoform of phosphatidylinositol 3-kinase (PI3K), in the embryonic mesoderm. Endothelial expression of Pik3ca(H1047R)resulted in endothelial cell (EC) hyperproliferation, reduction in pericyte coverage of blood vessels, and decreased expression of arteriovenous specification markers. PI3K pathway inhibition with rapamycin normalized EC hyperproliferation and pericyte coverage in postnatal retinas and stimulated VM regression in vivo. In line with the mouse data, we also report the presence of activating PIK3CA mutations in human VMs, mutually exclusive with TEK mutations. Our data demonstrate a causal relationship between activating Pik3ca mutations and the genesis of VMs, provide a genetic model that faithfully mirrors the normal etiology and development of this human disease, and establish the basis for the use of PI3K-targeted therapies in VMs.

  17. Deep Networks Can Resemble Human Feed-forward Vision in Invariant Object Recognition.

    PubMed

    Kheradpisheh, Saeed Reza; Ghodrati, Masoud; Ganjtabesh, Mohammad; Masquelier, Timothée

    2016-09-07

    Deep convolutional neural networks (DCNNs) have attracted much attention recently, and have shown to be able to recognize thousands of object categories in natural image databases. Their architecture is somewhat similar to that of the human visual system: both use restricted receptive fields, and a hierarchy of layers which progressively extract more and more abstracted features. Yet it is unknown whether DCNNs match human performance at the task of view-invariant object recognition, whether they make similar errors and use similar representations for this task, and whether the answers depend on the magnitude of the viewpoint variations. To investigate these issues, we benchmarked eight state-of-the-art DCNNs, the HMAX model, and a baseline shallow model and compared their results to those of humans with backward masking. Unlike in all previous DCNN studies, we carefully controlled the magnitude of the viewpoint variations to demonstrate that shallow nets can outperform deep nets and humans when variations are weak. When facing larger variations, however, more layers were needed to match human performance and error distributions, and to have representations that are consistent with human behavior. A very deep net with 18 layers even outperformed humans at the highest variation level, using the most human-like representations.

  18. Deep Networks Can Resemble Human Feed-forward Vision in Invariant Object Recognition

    PubMed Central

    Kheradpisheh, Saeed Reza; Ghodrati, Masoud; Ganjtabesh, Mohammad; Masquelier, Timothée

    2016-01-01

    Deep convolutional neural networks (DCNNs) have attracted much attention recently, and have shown to be able to recognize thousands of object categories in natural image databases. Their architecture is somewhat similar to that of the human visual system: both use restricted receptive fields, and a hierarchy of layers which progressively extract more and more abstracted features. Yet it is unknown whether DCNNs match human performance at the task of view-invariant object recognition, whether they make similar errors and use similar representations for this task, and whether the answers depend on the magnitude of the viewpoint variations. To investigate these issues, we benchmarked eight state-of-the-art DCNNs, the HMAX model, and a baseline shallow model and compared their results to those of humans with backward masking. Unlike in all previous DCNN studies, we carefully controlled the magnitude of the viewpoint variations to demonstrate that shallow nets can outperform deep nets and humans when variations are weak. When facing larger variations, however, more layers were needed to match human performance and error distributions, and to have representations that are consistent with human behavior. A very deep net with 18 layers even outperformed humans at the highest variation level, using the most human-like representations. PMID:27601096

  19. Genomic landscape of retinoblastoma in Rb(-/-) p130(-/-) mice resembles human retinoblastoma.

    PubMed

    Kooi, Irsan E; van Mil, Saskia E; MacPherson, David; Mol, Berber M; Moll, Annette C; Meijers-Heijboer, Hanne; Kaspers, Gertjan J L; Cloos, Jacqueline; Te Riele, Hein; Dorsman, Josephine C

    2017-03-01

    Several murine retinoblastoma models have been generated by deleting the genes encoding for retinoblastoma susceptibility protein pRb and one of its family members p107 or p130. In Rb(-/-) p107(-/-) retinoblastomas, somatic copy number alterations (SCNAs) like Mdm2 amplification or Cdkn2a deletion targeting the p53-pathway occur, which is uncommon for human retinoblastoma. In our study, we determined SCNAs in retinoblastomas developing in Rb(-/-) p130(-/-) mice and compared this to murine Rb(-/-) p107(-/-) tumors and human tumors. Chimeric mice were made by injection of 129/Ola-derived Rb(-/-) p130(-/-) embryonic stem cells into wild type C57BL/6 blastocysts. SCNAs of retinoblastoma samples were determined by low-coverage (∼0.5×) whole genome sequencing. In Rb(-/-) p130(-/-) tumors, SCNAs included gain of chromosomes 1 (3/23 tumors), 8 (1/23 tumors), 10 (1/23 tumors), 11 (2/23 tumors), and 12 (4/23 tumors), which could be mapped to frequently altered chromosomes in human retinoblastomas. While the altered chromosomes in Rb(-/-) p130(-/-) tumors were similar to those in Rb(-/-) p107(-/-) tumors, the alteration frequencies were much lower in Rb(-/-) p130(-/-) tumors. Most of the Rb(-/-) p130(-/-) tumors (16/23 tumors, 70%) were devoid of SCNAs, in strong contrast to Rb(-/-) p107(-/-) tumors, which were never (0/15 tumors) SCNA-devoid. Similarly, to human retinoblastoma, increased age at diagnosis significantly correlated with increased SCNA frequencies. Additionally, focal loss of Cdh11 was observed in one Rb(-/-) p130(-/-) tumor, which enforces studies in human retinoblastoma that identified CDH11 as a retinoblastoma suppressor. Moreover, based on a comparison of genes altered in human and murine retinoblastoma, we suggest exploring the role of HMGA1 and SRSF3 in retinoblastoma development. © 2016 Wiley Periodicals, Inc.

  20. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    PubMed Central

    2010-01-01

    Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV). Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift. PMID:20109187

  1. Animal cognition. Number-space mapping in the newborn chick resembles humans' mental number line.

    PubMed

    Rugani, Rosa; Vallortigara, Giorgio; Priftis, Konstantinos; Regolin, Lucia

    2015-01-30

    Humans represent numbers along a mental number line (MNL), where smaller values are located on the left and larger on the right. The origin of the MNL and its connections with cultural experience are unclear: Pre-verbal infants and nonhuman species master a variety of numerical abilities, supporting the existence of evolutionary ancient precursor systems. In our experiments, 3-day-old domestic chicks, once familiarized with a target number (5), spontaneously associated a smaller number (2) with the left space and a larger number (8) with the right space. The same number (8), though, was associated with the left space when the target number was 20. Similarly to humans, chicks associate smaller numbers with the left space and larger numbers with the right space.

  2. ATM deficiency promotes development of murine B-cell lymphomas that resemble diffuse large B-cell lymphoma in humans

    PubMed Central

    Hathcock, Karen S.; Padilla-Nash, Hesed M.; Camps, Jordi; Shin, Dong-Mi; Triner, Daniel; Shaffer, Arthur L.; Maul, Robert W.; Steinberg, Seth M.; Gearhart, Patricia J.; Staudt, Louis M.; Morse, Herbert C.; Ried, Thomas

    2015-01-01

    The serine-threonine kinase ataxia-telangiectasia mutated (ATM) plays a central role in maintaining genomic integrity. In mice, ATM deficiency is exclusively associated with T-cell lymphoma development, whereas B-cell tumors predominate in human ataxia-telangiectasia patients. We demonstrate in this study that when T cells are removed as targets for lymphomagenesis and as mediators of immune surveillance, ATM-deficient mice exclusively develop early-onset immunoglobulin M+ B-cell lymphomas that do not transplant to immunocompetent mice and that histologically and genetically resemble the activated B cell–like (ABC) subset of human diffuse large B-cell lymphoma (DLBCL). These B-cell lymphomas show considerable chromosomal instability and a recurrent genomic amplification of a 4.48-Mb region on chromosome 18 that contains Malt1 and is orthologous to a region similarly amplified in human ABC DLBCL. Of importance, amplification of Malt1 in these lymphomas correlates with their dependence on nuclear factor (NF)-κB, MALT1, and B-cell receptor (BCR) signaling for survival, paralleling human ABC DLBCL. Further, like some human ABC DLBCLs, these mouse B-cell lymphomas also exhibit constitutive BCR-dependent NF-κB activation. This study reveals that ATM protects against development of B-cell lymphomas that model human ABC DLBCL and identifies a potential role for T cells in preventing the emergence of these tumors. PMID:26400962

  3. Hydrogen-dependent organisms from the human gingival crevice resembling Vibrio succinogenes.

    PubMed

    Van Palenstein Helderman, W H; Rosman, I

    1976-01-01

    Twenty-eight strains of microaerophilic, motile, slightly curved gram-negative rods isolated from the gingival crevice of patients with gingivitis were studied. They seemed similar to Vibrio sputorum, though eleven strains differed in minor characters from Bergey's description under the new name Campylobacter sputorum, subspecies sputorum. The oral strains studied appeared to be closely related to several species of the genus Campylobacter and to Vibrio succinogenes. The oral strains were able to utilize gaseous hydrogen and to grow in a mineral medium with either nitrate of fumarate as hydrogen acceptor. Formate could replace hydrogen as hydrogen donor. In contrast the Campylobacter strains were not dependent on hydrogen or formate as energy source and grew poorly in mineral medium. In these nutritional and metabolic aspects the oral strains are more related to Vibrio succinogenes than to Campylobacter species. Serologically the oral strains differed from all the Campylobacter species. The GC ratio in the DNA of the oral strains varied between 48 and 50%, conform to the values described for Vibrio succinogenes. Vibrio sputorum seems a nomen conservandum and vibrio-like organisms from human infections should be tested for hydrogen-dependence before they are classified as Campylobacter species.

  4. Inclusion bodies in loggerhead erythrocytes are associated with unstable hemoglobin and resemble human Heinz bodies.

    PubMed

    Basile, Filomena; Di Santi, Annalisa; Caldora, Mercedes; Ferretti, Luigi; Bentivegna, Flegra; Pica, Alessandra

    2011-08-01

    The aim of this study was to clarify the role of the erythrocyte inclusions found during the hematological screening of loggerhead population of the Mediterranean Sea. We studied the erythrocyte inclusions in blood specimens collected from six juvenile and nine adult specimens of the loggerhead turtle, Caretta caretta, from the Adriatic and Tyrrhenian Seas. Our study indicates that the percentage of mature erythrocytes containing inclusions ranged from 3 to 82%. Each erythrocyte contained only one round inclusion body. Inclusion bodies stained with May Grünwald-Giemsa show that their cytochemical and ultrastructure characteristics are identical to those of human Heinz bodies. Because Heinz bodies originate from the precipitation of unstable hemoglobin (Hb) and cause globular osmotic resistance to increase, we analyzed loggerhead Hb using electrophoresis and high-performance liquid chromatography to detect and quantitate Hb fractions. We also tested the resistance of Hb to alkaline pH, heat, isopropanol denaturation, and globular osmosis. Our hemogram results excluded the occurrence of any infection, which could be associated with an inclusion body, in all the specimens. Negative Feulgen staining indicated that the inclusion bodies are not derived from DNA fragmentation. We hypothesize that amino acid substitutions could explain why loggerhead Hb precipitates under normal physiologic conditions, forming Heinz bodies. The identification of inclusion bodies in loggerhead erythrocytes allow us to better understand the haematological characteristics and the physiology of these ancient reptiles, thus aiding efforts to conserve such an endangered species.

  5. The RNA Binding Specificity of Human APOBEC3 Proteins Resembles That of HIV-1 Nucleocapsid

    PubMed Central

    Errando, Manel; Bieniasz, Paul D.

    2016-01-01

    The APOBEC3 (A3) cytidine deaminases are antiretroviral proteins, whose targets include human immunodeficiency virus type-1 (HIV-1). Their incorporation into viral particles is critical for antiviral activity and is driven by interactions with the RNA molecules that are packaged into virions. However, it is unclear whether A3 proteins preferentially target RNA molecules that are destined to be packaged and if so, how. Using cross-linking immunoprecipitation sequencing (CLIP-seq), we determined the RNA binding preferences of the A3F, A3G and A3H proteins. We found that A3 proteins bind preferentially to RNA segments with particular properties, both in cells and in virions. Specifically, A3 proteins target RNA sequences that are G-rich and/or A-rich and are not scanned by ribosomes during translation. Comparative analyses of HIV-1 Gag, nucleocapsid (NC) and A3 RNA binding to HIV-1 RNA in cells and virions revealed the striking finding that A3 proteins partially mimic the RNA binding specificity of the HIV-1 NC protein. These findings suggest a model for A3 incorporation into HIV-1 virions in which an NC-like RNA binding specificity is determined by nucleotide composition rather than sequence. This model reconciles the promiscuity of A3 RNA binding that has been observed in previous studies with a presumed advantage that would accompany selective binding to RNAs that are destined to be packaged into virions. PMID:27541140

  6. Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis.

    PubMed

    Matsuzaki, K

    2006-06-01

    Transforming growth factor-beta (TGF-beta) signaling occurring during human colorectal carcinogenesis involves a shift in TGF-beta function, reducing the cytokine's antiproliferative effect, while increasing actions that promote invasion and metastasis. TGF-beta signaling involves phosphorylation of Smad3 at serine residues 208 and 213 in the linker region and serine residues 423 and 425 in the C-terminal region. Exogenous TGF-beta activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), changing unphosphorylated Smad3 to its phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker phosphorylated Smad3 (pSmad3L). Either pSmad3C or pSmad3L oligomerizes with Smad4, and translocates into nuclei. While the TbetaRI/pSmad3C pathway inhibits growth of normal epithelial cells in vivo, JNK/pSmad3L-mediated signaling promotes tumor cell invasion and extracellular matrix synthesis by activated mesenchymal cells. Furthermore, hepatocyte growth factor signaling interacts with TGF-beta to activate the JNK/pSmad3L pathway, accelerating nuclear transport of cytoplasmic pSmad3L. This reduces accessibility of unphosphorylated Smad3 to membrane-anchored TbetaRI, preventing Smad3C phosphorylation, pSmad3C-mediated transcription, and antiproliferative effects of TGF-beta on epithelial cells. As neoplasia progresses from normal colorectal epithelium through adenoma to invasive adenocarcinoma with distant metastasis, nuclear pSmad3L gradually increases while pSmad3C decreases. The shift from TbetaRI/pSmad3C-mediated to JNK/pSmad3L-mediated signaling is a major mechanism orchestrating a complex transition of TGF-beta signaling during sporadic human colorectal carcinogenesis. This review summarizes the recent understanding of Smad3 phosphoisoform-mediated signaling, particularly 'cross-talk' between Smad3 and JNK pathways that cooperatively promote oncogenic activities. Understanding of these actions should help to develop more effective

  7. Human Glioma–Initiating Cells Show a Distinct Immature Phenotype Resembling but Not Identical to NG2 Glia

    PubMed Central

    Barrantes-Freer, Alonso; Kim, Ella; Bielanska, Joanna; Giese, Alf; Mortensen, Lena Sünke; Schulz-Schaeffer, Walter J.; Stadelmann, Christine; Brück, Wolfgang

    2013-01-01

    Abstract Glioma-initiating cells (GICs) represent a potential important therapeutic target because they are likely to account for the frequent recurrence of malignant gliomas; however, their identity remains unsolved. Here, we characterized the cellular lineage fingerprint of GICs through a combination of electrophysiology, lineage marker expression, and differentiation assays of 5 human patient-derived primary GIC lines. Most GICs coexpressed nestin, NG2 proteoglycan, platelet-derived growth factor receptor-α, and glial fibrillary acidic protein. Glioma-initiating cells could be partially differentiated into astrocytic but not oligodendroglial or neural lineages. We also demonstrate that GICs have a characteristic electrophysiologic profile distinct from that of well-characterized tumor bulk cells. Together, our results suggest that GICs represent a unique type of cells reminiscent of an immature phenotype that closely resembles but is not identical to NG2 glia with respect to marker expression and functional membrane properties. PMID:23481707

  8. A skeletal disorder in a dog resembling the Klippel-Feil Syndrome with Sprengel's Deformity in humans.

    PubMed

    Bertolini, G; Trotta, M; Caldin, M

    2015-03-01

    A five-year-old intact male golden retriever dog was evaluated for cervical pain and right hemiparesis. Clinical and computed tomography features suggested a caudal cervical instability and myelopathy due to a cervicoscapular malformation resembling the human Klippel-Feil Syndrome with Sprengel Deformity, a rare complex congenital disorder. Polymerase chain reaction (PCR) and direct sequencing of MEOX1, PAX1 and FGFR3 genes were performed in this dog to investigate a possible underlying genetic predisposition, but no mutations were detected in the coding regions of the three target genes evaluated. Other genes can be involved in this condition in dogs and require further investigation. This report describes a cervical vertebral fusion and complex scapular anomaly in a dog. The presence of an omovertebral bone should be considered in the setting of signs characteristic of myelopathy in dogs with or without obvious skeletal deformity.

  9. Nicotine Delivery to Rats via Lung Alveolar Region-Targeted Aerosol Technology Produces Blood Pharmacokinetics Resembling Human Smoking

    PubMed Central

    2013-01-01

    Introduction: Nicotine is a heavily used addictive drug acquired through smoking tobacco. Nicotine in cigarette smoke is deposited and absorbed in the lungs, which results in a rapidly peaked slowly declining arterial concentration. This pattern plays an important role in initiation of nicotine addiction. Methods: A method and device were developed for delivering nicotine to rodents with lung alveolar region-targeted aerosol technology. The dose of delivery can be controlled by the nicotine aerosol concentration and duration of exposure. Results: Our data showed that, in the breathing zone of the nose-only exposure chamber, the aerosol droplet size distribution was within the respirable diameter range. Rats were exposed to nicotine aerosol for 2min. The arterial blood nicotine concentration reached 43.2±15.7ng/ml (mean ± SD) within 1–4min and declined over the next 20min, closely resembling the magnitude and early pharmacokinetics of a human smoking a cigarette. The acute inhalation toxicity of nicotine: LC50 = 2.3mg/L was determined; it was affected by pH, suggesting that acidification decreases nicotine absorption and/or bioavailability. Conclusions: A noninvasive method and toolkit were developed for delivering nicotine to rodents that enable rapid delivery of a controllable amount of nicotine into the systemic circulation and brain-inducing dose-dependent pharmacological effects, even a lethal dose. Aerosol inhalation can produce nicotine kinetics in both arterial and venous blood resembling human smoking. This method can be applied to studies of the effects of chronic intermittent nicotine exposure, nicotine addiction, toxicology, tobacco-related diseases, teratogenicity, and for discovery of pharmacological therapeutics. PMID:23239844

  10. Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

    PubMed Central

    Wong-Baeza, Carlos; Reséndiz-Mora, Albany; Donis-Maturano, Luis; Wong-Baeza, Isabel; Zárate-Neira, Luz; Yam-Puc, Juan Carlos; Calderón-Amador, Juana; Medina, Yolanda; Wong, Carlos; Baeza, Isabel; Flores-Romo, Leopoldo

    2016-01-01

    Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers. PMID:27746783

  11. On the lack of evidence that non-human animals possess anything remotely resembling a 'theory of mind'.

    PubMed

    Penn, Derek C; Povinelli, Daniel J

    2007-04-29

    After decades of effort by some of our brightest human and non-human minds, there is still little consensus on whether or not non-human animals understand anything about the unobservable mental states of other animals or even what it would mean for a non-verbal animal to understand the concept of a 'mental state'. In the present paper, we confront four related and contentious questions head-on: (i) What exactly would it mean for a non-verbal organism to have an 'understanding' or a 'representation' of another animal's mental state? (ii) What should (and should not) count as compelling empirical evidence that a non-verbal cognitive agent has a system for understanding or forming representations about mental states in a functionally adaptive manner? (iii) Why have the kind of experimental protocols that are currently in vogue failed to produce compelling evidence that non-human animals possess anything even remotely resembling a theory of mind? (iv) What kind of experiments could, at least in principle, provide compelling evidence for such a system in a non-verbal organism?

  12. PLTP secreted by HepG2 cells resembles the high-activity PLTP form in human plasma.

    PubMed

    Siggins, Sarah; Jauhiainen, Matti; Olkkonen, Vesa M; Tenhunen, Jukka; Ehnholm, Christian

    2003-09-01

    Plasma phospholipid transfer protein (PLTP) is an important regulator of plasma HDL levels and HDL particle distribution. PLTP is present in plasma in two forms, one with high and the other with low phospholipid transfer activity. We have used the human hepatoma cell line, HepG2, as a model to study PLTP secreted from hepatic cells. PLTP activity was secreted by the cells into serum-free culture medium as a function of time. However, modification of a previously established ELISA assay to include a denaturing sample pretreatment with the anionic detergent sodium dodecyl sulphate was required for the detection of the secreted PLTP protein. The HepG2 PLTP could be enriched by Heparin-Sepharose affinity chromatography and eluted in size-exclusion chromatography at a position corresponding to the size of 160 kDa. PLTP coeluted with apolipoprotein E (apoE) but not with apoB-100 or apoA-I. A portion of PLTP was retained by an anti-apoE immunoaffinity column together with apoE, suggesting an interaction between these two proteins. Furthermore, antibodies against apoE but not those against apoB-100 or apoA-I were capable of inhibiting PLTP activity. These results show that the HepG2-derived PLTP resembles in several aspects the high-activity form of PLTP found in human plasma.

  13. Calpain 1 inhibitor BDA-410 ameliorates α-klotho-deficiency phenotypes resembling human aging-related syndromes

    PubMed Central

    Nabeshima, Yoko; Washida, Miwa; Tamura, Masaru; Maeno, Akiteru; Ohnishi, Mutsuko; Shiroishi, Toshihiko; Imura, Akihiro; Razzaque, M. Shawkat; Nabeshima, Yo-ichi

    2014-01-01

    Taking good care of elderly is a major challenge of our society, and thus identification of potential drug targets to reduce age-associated disease burden is desirable. α-klotho-/- (α-kl) is a short-lived mouse model that displays multiple phenotypes resembling human aging-related syndromes. Such ageing phenotype of α-kl-/- mice is associated with activation of a proteolytic enzyme, Calpain-1. We hypothesized that uncontrolled activation of calpain-1 might be causing age-related phenotypes in α-kl-deficient mice. We found that daily administration of BDA-410, a calpain-1 inhibitor, strikingly ameliorated multiple aging-related phenotypes. Treated mice showed recovery of reproductive ability, increased body weight, reduced organ atrophy, and suppression of ectopic calcifications, bone mineral density reduction, pulmonary emphysema and senile atrophy of skin. We also observed ectopic expression of FGF23 in calcified arteries of α-kl-/- mice, which might account for the clinically observed association of increased FGF23 level with increased risk of cardiovascular mortality. These findings allow us to propose that modulation of calpain-1 activity is a potential therapeutic option for delaying age-associated organ pathology, particularly caused by the dysregulation of mineral ion homeostasis. PMID:25080854

  14. Does Facial Resemblance Enhance Cooperation?

    PubMed Central

    Giang, Trang; Bell, Raoul; Buchner, Axel

    2012-01-01

    Facial self-resemblance has been proposed to serve as a kinship cue that facilitates cooperation between kin. In the present study, facial resemblance was manipulated by morphing stimulus faces with the participants' own faces or control faces (resulting in self-resemblant or other-resemblant composite faces). A norming study showed that the perceived degree of kinship was higher for the participants and the self-resemblant composite faces than for actual first-degree relatives. Effects of facial self-resemblance on trust and cooperation were tested in a paradigm that has proven to be sensitive to facial trustworthiness, facial likability, and facial expression. First, participants played a cooperation game in which the composite faces were shown. Then, likability ratings were assessed. In a source memory test, participants were required to identify old and new faces, and were asked to remember whether the faces belonged to cooperators or cheaters in the cooperation game. Old-new recognition was enhanced for self-resemblant faces in comparison to other-resemblant faces. However, facial self-resemblance had no effects on the degree of cooperation in the cooperation game, on the emotional evaluation of the faces as reflected in the likability judgments, and on the expectation that a face belonged to a cooperator rather than to a cheater. Therefore, the present results are clearly inconsistent with the assumption of an evolved kin recognition module built into the human face recognition system. PMID:23094095

  15. Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma.

    PubMed

    Undén, A B; Zaphiropoulos, P G; Bruce, K; Toftgård, R; Ståhle-Bäckdahl, M

    1997-06-15

    Recently, a human homologue of the Drosophila patched gene, PTCH, was identified as a putative tumor suppressor mutated in both hereditary and sporadic basal cell carcinomas. Because PTCH controls its own transcription, inactivating mutations in PTCH may lead to overexpression of mutant PTCH mRNA due to loss of autoregulation. The present study is aimed at evaluating whether deregulation of PTCH mRNA expression is a general feature of BCCs of varying histological growth pattern and malignant potential. Irrespective of histological subtype, PTCH mRNA was overexpressed consistently as determined by in situ hybridization in all of the sporadic (n = 16) and hereditary (n = 20) tumors examined. PTCH expression was found in all of the tumor cells but appeared stronger in the peripheral palisading cells. PTCH mRNA was not detected in adjacent nontumor epidermal cells or in other parts of the epidermis. In the majority of tumors (20 of 36), nuclear immunostaining for p53 was found in scattered cells, whereas seven tumors completely lacked p53 immunoreactivity. Our finding of an up-regulation of PTCH mRNA levels in all of the BCCs analyzed indicates that deregulation of the PTCH signaling pathway constitutes an early rate-limiting event in BCC development.

  16. Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

    PubMed Central

    Alves, Chrystian J.; Dariolli, Rafael; Jorge, Frederico M.; Monteiro, Matheus R.; Maximino, Jessica R.; Martins, Roberto S.; Strauss, Bryan E.; Krieger, José E.; Callegaro, Dagoberto; Chadi, Gerson

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that leads to widespread motor neuron death, general palsy and respiratory failure. The most prevalent sporadic ALS form is not genetically inherited. Attempts to translate therapeutic strategies have failed because the described mechanisms of disease are based on animal models carrying specific gene mutations and thus do not address sporadic ALS. In order to achieve a better approach to study the human disease, human induced pluripotent stem cell (hiPSC)-differentiated motor neurons were obtained from motor nerve fibroblasts of sporadic ALS and non-ALS subjects using the STEMCCA Cre-Excisable Constitutive Polycistronic Lentivirus system and submitted to microarray analyses using a whole human genome platform. DAVID analyses of differentially expressed genes identified molecular function and biological process-related genes through Gene Ontology. REVIGO highlighted the related functions mRNA and DNA binding, GTP binding, transcription (co)-repressor activity, lipoprotein receptor binding, synapse organization, intracellular transport, mitotic cell cycle and cell death. KEGG showed pathways associated with Parkinson's disease and oxidative phosphorylation, highlighting iron homeostasis, neurotrophic functions, endosomal trafficking and ERK signaling. The analysis of most dysregulated genes and those representative of the majority of categorized genes indicates a strong association between mitochondrial function and cellular processes possibly related to motor neuron degeneration. In conclusion, iPSC-derived motor neurons from motor nerve fibroblasts of sporadic ALS patients may recapitulate key mechanisms of neurodegeneration and may offer an opportunity for translational investigation of sporadic ALS. Large gene profiling of differentiated motor neurons from sporadic ALS patients highlights mitochondrial participation in the establishment of autonomous mechanisms associated with sporadic ALS

  17. Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration.

    PubMed

    Alves, Chrystian J; Dariolli, Rafael; Jorge, Frederico M; Monteiro, Matheus R; Maximino, Jessica R; Martins, Roberto S; Strauss, Bryan E; Krieger, José E; Callegaro, Dagoberto; Chadi, Gerson

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that leads to widespread motor neuron death, general palsy and respiratory failure. The most prevalent sporadic ALS form is not genetically inherited. Attempts to translate therapeutic strategies have failed because the described mechanisms of disease are based on animal models carrying specific gene mutations and thus do not address sporadic ALS. In order to achieve a better approach to study the human disease, human induced pluripotent stem cell (hiPSC)-differentiated motor neurons were obtained from motor nerve fibroblasts of sporadic ALS and non-ALS subjects using the STEMCCA Cre-Excisable Constitutive Polycistronic Lentivirus system and submitted to microarray analyses using a whole human genome platform. DAVID analyses of differentially expressed genes identified molecular function and biological process-related genes through Gene Ontology. REVIGO highlighted the related functions mRNA and DNA binding, GTP binding, transcription (co)-repressor activity, lipoprotein receptor binding, synapse organization, intracellular transport, mitotic cell cycle and cell death. KEGG showed pathways associated with Parkinson's disease and oxidative phosphorylation, highlighting iron homeostasis, neurotrophic functions, endosomal trafficking and ERK signaling. The analysis of most dysregulated genes and those representative of the majority of categorized genes indicates a strong association between mitochondrial function and cellular processes possibly related to motor neuron degeneration. In conclusion, iPSC-derived motor neurons from motor nerve fibroblasts of sporadic ALS patients may recapitulate key mechanisms of neurodegeneration and may offer an opportunity for translational investigation of sporadic ALS. Large gene profiling of differentiated motor neurons from sporadic ALS patients highlights mitochondrial participation in the establishment of autonomous mechanisms associated with sporadic ALS.

  18. Regulation of human cerebrospinal fluid malate dehydrogenase 1 in sporadic Creutzfeldt-Jakob disease patients

    PubMed Central

    Schmitz, Matthias; Llorens, Franc; Pracht, Alexander; Thom, Tobias; Correia, Ângela; Zafar, Saima; Ferrer, Isidre; Zerr, Inga

    2016-01-01

    The identification of reliable diagnostic biomarkers in differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous two-dimensional proteomic study on cerebrospinal fluid (CSF) revealed an elevated level of an enzyme, mitochondrial malate dehydrogenase 1 (MDH1), in sporadic Creutzfeldt-Jakob disease (sCJD) patients. Here, we could demonstrate the expression of MDH1 in neurons as well as in the neuropil. Its levels are lower in sCJD brains than in control brains. An examination of CSF-MDH1 in sCJD patients by ELISA revealed a significant elevation of CSF-MDH1 levels in sCJD patients (independently from the PRNP codon 129 MV genotype or the prion protein scrapie (PrPSc) type) in comparison to controls. In combination with total tau (tau), CSF-MDH1 detection exhibited a high diagnostic accuracy for sCJD diagnosis with a sensitivity of 97.5% and a specificity of 95.6%. A correlation study of MDH1 level in CSF with other neurodegenerative marker proteins revealed a significant positive correlation between MDH1 concentration with tau, 14-3-3 and neuron specific enolase level. In conclusion, our study indicated the potential of MDH1 in combination with tau as an additional biomarker in sCJD improving diagnostic accuracy of tau markedly. PMID:27852982

  19. Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma

    SciTech Connect

    Burmer, G.C.; Rabinovitch, P.S.; Loeb, L.A. )

    1991-06-01

    Sporadic colon carcinomas, carcinomas arising in chronic ulcerative colitis, and pancreatic adenocarcinomas have been analyzed for the presence of c-Ki-ras mutations by a combination of histological enrichment, cell sorting, polymerase chain reaction, and direct sequencing. Although 60% (37/61) of sporadic colon carcinomas contained mutations in codon 12, only 1 of 17 specimens of dysplasia or carcinoma from ulcerative colitis patients contained c-Ki-ras mutations, despite a high frequency of aneuploid tumors. In contrast, a higher percentage (16/20 = 80%) of pancreatic adenocarcinomas contained mutations in c-Ki-ras 2, despite a lower frequency of DNA aneuploidy in these neoplasms. Moreover, the spectrum of mutations differed between sporadic colon carcinoma, where the predominant mutation was a G to A transition, and pancreatic carcinomas, which predominantly contained G to C or T transversions. These results suggest that the etiology of ras mutations is different in these three human neoplasms.

  20. Species composition of phlebotomine sand fly fauna in an area with sporadic cases of Leishmania infantum human visceral leishmaniasis, Morocco.

    PubMed

    Kahime, Kholoud; Boussaa, Samia; Ouanaimi, Fouad; Boumezzough, Ali

    2015-08-01

    Visceral and cutaneous leishmaniases are the main endemic vector-born diseases in Morocco. Human visceral leishmaniasis (HVL), by Leishmania infantum, currently presents a significant health problem throughout the country and may constitute factor for death, especially among children with less than 15 years old. In the past, HVL has been basically absent or at least sporadic in Marrakesh-Tensift-Al Haouz region; however it became significant during the last decade. An entomological survey and a retrospective study on L. infantum HVL cases had been carried out to assess the risk of the disease apparition in this region. 7046 sand flies (Diptera: Psychodidae) were collected and studied from twelve localities within Marrakesh-Tensift-Al Haouz region. The result shows the presence of ten sand fly species, 58.76% from the genus Phlebotomus and 41.24% from genus Sergentomyia. A further analysis indicates that Phlebotomus perniciosus, Phlebotomus longicuspis and Phlebotomus ariasi species, incriminated vectors of L. infantum, are dominant (35.56%), so, we describe their spatial (according to altitude and biotopes) and temporal (seasonal activity) distribution in study area.

  1. Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease

    PubMed Central

    Sánchez-Danés, Adriana; Richaud-Patin, Yvonne; Carballo-Carbajal, Iria; Jiménez-Delgado, Senda; Caig, Carles; Mora, Sergio; Di Guglielmo, Claudia; Ezquerra, Mario; Patel, Bindiben; Giralt, Albert; Canals, Josep M; Memo, Maurizio; Alberch, Jordi; López-Barneo, José; Vila, Miquel; Cuervo, Ana Maria; Tolosa, Eduard; Consiglio, Antonella; Raya, Angel

    2012-01-01

    Induced pluripotent stem cells (iPSC) offer an unprecedented opportunity to model human disease in relevant cell types, but it is unclear whether they could successfully model age-related diseases such as Parkinson's disease (PD). Here, we generated iPSC lines from seven patients with idiopathic PD (ID-PD), four patients with familial PD associated to the G2019S mutation in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene (LRRK2-PD) and four age- and sex-matched healthy individuals (Ctrl). Over long-time culture, dopaminergic neurons (DAn) differentiated from either ID-PD- or LRRK2-PD-iPSC showed morphological alterations, including reduced numbers of neurites and neurite arborization, as well as accumulation of autophagic vacuoles, which were not evident in DAn differentiated from Ctrl-iPSC. Further induction of autophagy and/or inhibition of lysosomal proteolysis greatly exacerbated the DAn morphological alterations, indicating autophagic compromise in DAn from ID-PD- and LRRK2-PD-iPSC, which we demonstrate occurs at the level of autophagosome clearance. Our study provides an iPSC-based in vitro model that captures the patients' genetic complexity and allows investigation of the pathogenesis of both sporadic and familial PD cases in a disease-relevant cell type. PMID:22407749

  2. Expression of cell growth negative regulators MEG3 and GADD45γ is lost in most sporadic human pituitary adenomas.

    PubMed

    Mezzomo, Lisiane Cervieri; Gonzales, Paulo Henrique; Pesce, Frederico Giacomoni; Kretzmann Filho, Nélson; Ferreira, Nelson Pires; Oliveira, Miriam Costa; Kohek, Maria Beatriz Fonte

    2012-09-01

    We aimed at the evaluation of MEG3 and GADD45γ expression in sporadic functioning and clinically non-functioning human pituitary adenomas, morphologically characterized by immunohistochemistry analysis and their association with clinical features. Thirty eight patients who had undergone hypophysectomy at São José Hospital of Irmandade Santa Casa de Misericórdia in Porto Alegre, Brazil, were included in this study. We evaluated tumor-type specific MEG3 and GADD45γ expression by qRT-PCR in the pituitary adenomas, and its association with clinical features, as age, gender and tumor size, obtained from medical records. The patients consisted of 21 males and 17 females and the mean age was 47 ± 14 (mean ± SD), ranging from 18 to 73 years-old. Of these 14 were clinically non-functioning, 10 GH-secreting, 9 PRL-secreting, and 5 ACTH-secreting pituitary adenomas. All samples were macroadenomas, except four ACTH-secreting tumors, which were microadenomas. In summary, MEG3 and GADD45γ expression was significantly lost in most clinically non-functioning adenomas (78 and 92%, respectively). Other assessed pituitary tumor phenotypes expressed both genes at significantly different levels, and, in some cases, with overexpression. There was no significant association between gene expression and the analyzed clinical features. Our results confirm the previous report, which indicated that MEG3 and GADD45γ expression is lost in the majority of human pituitary tumors, mainly in clinically-nonfunctioning adenomas. Functioning tumors had differences of relative expression levels. The two groups of tumors are probably genetically different and may have a different natural history.

  3. MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer's Disease (AD)-Novel and Unique Pathological Features.

    PubMed

    Zhao, Yuhai; Pogue, Aileen I; Lukiw, Walter J

    2015-12-17

    Of the approximately ~2.65 × 10³ mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset-about 35-40-are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA-mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer's disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS.

  4. Genetic determinants for cadmium and arsenic resistance among Listeria monocytogenes serotype 4b isolates from sporadic human listeriosis patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Listeria monocytogenes serotype 4b from sporadic listeriosis, heavy metal resistance was primarily encountered in certain clonal groups (ECI, ECII, ECIa). All arsenic-resistant isolates harbored the arsenic resistance cassette previously identified in pLI100; ECIa harbored additional arsenic resi...

  5. Population Structure of Listeria monocytogenes Serotype 4b Isolates from Sporadic Human Listeriosis in the United States, 2003-2008

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes can cause severe foodborne disease (listeriosis). Serotype 4b strains have resulted in numerous outbreaks, repeatedly involving three epidemic clones (ECI, ECII, and ECIa). Little is known about population structure of L. monocytogenes serotype 4b from sporadic listeriosis, ev...

  6. Hemangiomatosis associated with osteolysis of the mandible in a dog resembling Gorham-Stout disease in humans.

    PubMed

    López Peña, M; Muñoz, F; Alemañ, N; González, A; Pereira, J L; Nieto, J M

    2005-07-01

    A 6-month-old female German Shepherd Dog died as a result of profuse oral bleeding. At postmortem examination, the oral cavity showed visible roots of the right mandibular fourth premolar and first molar teeth and, in addition, they were very mobile and compressible. Radiographs showed a generalized radiolucency in the body of the right mandible, with evidence of resorption of the affected alveolar bone. Histologically, the lesion of the right mandible was characterized by the lysis of bony structures and a non-malignant proliferation of blood-filled vascular spaces lined by a single layer of well-differentiated endothelial cells. The clinical, radiographic, and histologic presentation of this dog is consistent with that associated with Gorham-Stout disease, a rare bone disorder in humans.

  7. Characterization of naturally occurring cutaneous neurofibromatosis in Holstein cattle. A disorder resembling neurofibromatosis type 1 in humans.

    PubMed Central

    Sartin, E. A.; Doran, S. E.; Riddell, M. G.; Herrera, G. A.; Tennyson, G. S.; D'Andrea, G.; Whitley, R. D.; Collins, F. S.

    1994-01-01

    Neurofibromatosis in cattle is typically a noncutaneous disease. A small group of cows in a Holstein dairy herd developed cutaneous neurofibromatosis. This unique condition was investigated and compared with neurofibromatosis type 1 (NF1) in humans. All cutaneous lesions but one were consistent with neurofibromas in noncutaneous sites in cattle and neurofibromas in patients with NF1. One bovine lesion was classified as a neurofibrosarcoma. Immunohistochemistry and electron microscopy supported Schwannian differentiation in benign and malignant lesions. Linkage analysis with a polymorphism in the bovine NF1 gene confirmed that two affected animals from the same sire inherited the same paternal NF1 allele. Bovine cutaneous neurofibromatosis is a naturally occurring disease in this group of animals, characterized by skin tumors morphologically identical to those of NF1. An informative polymorphism at the NF1 locus of two animals and their sire suggests this disorder may be caused by hereditary mutations at the bovine NF1 locus. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:7977647

  8. Cancer driver-passenger distinction via sporadic human and dog cancer comparison: a proof-of-principle study with colorectal cancer.

    PubMed

    Tang, J; Li, Y; Lyon, K; Camps, J; Dalton, S; Ried, T; Zhao, S

    2014-02-13

    Herein we report a proof-of-principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver-passenger distinction. We previously demonstrated that sporadic canine colorectal cancers (CRCs) share similar molecular pathogenesis mechanisms as their human counterparts. In this study, we compared the genome-wide copy number abnormalities between 29 human and 10 canine sporadic CRCs. This led to the identification of 73 driver candidate genes (DCGs), altered in both species, and with 27 from the whole genome and 46 from dog-human genomic rearrangement breakpoint (GRB) regions, as well as 38 passenger candidate genes (PCGs), altered in humans only and located in GRB regions. We noted that DCGs significantly differ from PCGs in every analysis conducted to assess their cancer relevance and biological functions. Importantly, although PCGs are not enriched in any specific functions, DCGs possess significantly enhanced functionality closely associated with cell proliferation and death regulation, as well as with epithelial cell apicobasal polarity establishment/maintenance. These observations support the notion that, in sporadic CRCs of both species, cell polarity genes not only contribute in preventing cancer cell invasion and spreading, but also likely serve as tumor suppressors by modulating cell growth. This pilot study validates our novel strategy and has uncovered four new potential cell polarity and colorectal tumor suppressor genes (RASA3, NUPL1, DENND5A and AVL9). Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals.

  9. Molecular subtyping by genome and plasmid analysis of Campylobacter jejuni serogroups O1 and O2 (Penner) from sporadic and outbreak cases of human diarrhoea.

    PubMed Central

    Fayos, A.; Owen, R. J.; Hernandez, J.; Jones, C.; Lastovica, A.

    1993-01-01

    Ribosomal RNA gene patterns, randomly amplified polymorphic genomic DNA (RAPD) profiles and plasmid profiles were used to discriminate between 28 strains of Campylobacter jejuni serogroups O1 and O2 (Penner). Most isolates were biotype I (Lior). The strains were representative isolates from a UK school outbreak of enteritis (7 cases) and from 21 sporadic human cases of enteritis in 4 countries. The molecular techniques discriminated to various degrees between strains in each of the serogroups. The outbreak strains were homogeneous in most molecular features but a variety of types was detected amongst the isolates from the sporadic cases. Five groups of two or more strains with identical ribopatterns were identified and within each, strains from different patients were homogenous with respect to serogroup. RAPD profile typing based on numerical analysis generally matched ribotyping. Plasmid profiling overall gave least discrimination but was useful in separating some strains similar in other features. We concluded that optimal discrimination of C. jejuni could best be achieved using a combination of phenotypic and genotypic properties. Hae III ribotyping was the single most discriminatory and reproducible technique investigated. Several strains of C. jejuni from sporadic infections had similar molecular profiles which have potential for general typing purposes. Images Fig. 1 Fig. 3 PMID:7505748

  10. MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer’s Disease (AD)-Novel and Unique Pathological Features

    PubMed Central

    Zhao, Yuhai; Pogue, Aileen I.; Lukiw, Walter J.

    2015-01-01

    Of the approximately ~2.65 × 103 mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset—about 35–40—are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA–mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer’s disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS. PMID:26694372

  11. Human XCR1+ Dendritic Cells Derived In Vitro from CD34+ Progenitors Closely Resemble Blood Dendritic Cells, Including Their Adjuvant Responsiveness, Contrary to Monocyte-Derived Dendritic Cells

    PubMed Central

    Balan, Sreekumar; Ollion, Vincent; Colletti, Nicholas; Chelbi, Rabie; Montanana-Sanchis, Frédéric; Liu, Hong; Vu Manh, Thien-Phong; Sanchez, Cindy; Savoret, Juliette; Perrot, Ivan; Doffin, Anne-Claire; Fossum, Even; Bechlian, Didier; Chabannon, Christian; Bogen, Bjarne; Asselin-Paturel, Carine; Shaw, Michael; Soos, Timothy; Caux, Christophe; Valladeau-Guilemond, Jenny

    2014-01-01

    Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1+ DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1+ human DC. Assessment of the immunoactivation potential of XCR1+ human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1+ and XCR1− human DC in CD34+ progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1− CD34-DC are similar to canonical MoDC, whereas XCR1+ CD34-DC resemble XCR1+ blood DC (bDC). XCR1+ DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1+ DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1+ CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1+ bDC. Hence, it is feasible to generate high numbers of bona fide XCR1+ human DC in vitro as a model to decipher the functions of XCR1+ bDC and as a potential source of XCR1+ DC for clinical use. PMID:25009205

  12. Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation.

    PubMed

    Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars

    2011-01-01

    Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

  13. Evolution of alpha 2-macroglobulin. The demonstration in a variety of vertebrate species of a protein resembling human alpha 2-macroglobulin.

    PubMed Central

    Starkey, P M; Barrett, A J

    1982-01-01

    Plasma or serum samples from a large number of vertebrate species were screened for the presence of a papain-binding protein resembling human alph a 2-macroglobulin (alpha 2M). The screening method depended on the unique property of alpha 2M of binding proteinases in such a way that the enzyme retains partial activity against low-molecular-weight substrates. A papain-binding protein was detected in serum from members of all the major vertebrate taxa. In mammals, birds, reptiles and amphibians the protein had an Mr similar to that of human alpha 2M (725 000), but in fish, including dipnoans, actinopterygians, elasmobranchs and cyclostomes, the papain-binding protein was of Mr about 360 000. Of the invertebrate species tested, all of which were arthropods, two were negative, but the horseshoe crab, an arachnid, did possess a papain-binding protein, although this was heterogeneous in electrophoresis and differed from alpha 2M in resisting inactivation by methylamine. From the results, and a detailed study of the properties of the fish papain-binding protein described in an accompanying paper [Starkey, Fletcher & Barrett (1982) Biochem. J. 205, 97-104], it seems that alpha 2M first appeared in an ancestor of all modern vertebrates as a protein of Mr 360 000 and that the larger macroglobulin (Mr 725 000) first appeared in an ancestor of the tetrapods. Images Fig. 1. PMID:6181778

  14. Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

    PubMed Central

    Wong-Baeza, Carlos; Tescucano, Alonso; Astudillo, Horacio; Reséndiz, Albany; Landa, Carla; España, Luis; Serafín-López, Jeanet; Estrada-García, Iris; Estrada-Parra, Sergio; Flores-Romo, Leopoldo; Wong, Carlos; Baeza, Isabel

    2015-01-01

    Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR) signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK) cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice. PMID:26568960

  15. Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus.

    PubMed

    Wong-Baeza, Carlos; Tescucano, Alonso; Astudillo, Horacio; Reséndiz, Albany; Landa, Carla; España, Luis; Serafín-López, Jeanet; Estrada-García, Iris; Estrada-Parra, Sergio; Flores-Romo, Leopoldo; Wong, Carlos; Baeza, Isabel

    2015-01-01

    Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR) signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK) cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice.

  16. Simultaneous effects on parvalbumin-positive interneuron and dopaminergic system development in a transgenic rat model for sporadic schizophrenia

    PubMed Central

    Hamburg, Hannah; Trossbach, Svenja V.; Bader, Verian; Chwiesko, Caroline; Kipar, Anja; Sauvage, Magdalena; Crum, William R.; Vernon, Anthony C.; Bidmon, Hans J.; Korth, Carsten

    2016-01-01

    To date, unequivocal neuroanatomical features have been demonstrated neither for sporadic nor for familial schizophrenia. Here, we investigated the neuroanatomical changes in a transgenic rat model for a subset of sporadic chronic mental illness (CMI), which modestly overexpresses human full-length, non-mutant Disrupted-in-Schizophrenia 1 (DISC1), and for which aberrant dopamine homeostasis consistent with some schizophrenia phenotypes has previously been reported. Neuroanatomical analysis revealed a reduced density of dopaminergic neurons in the substantia nigra and reduced dopaminergic fibres in the striatum. Parvalbumin-positive interneuron occurrence in the somatosensory cortex was shifted from layers II/III to V/VI, and the number of calbindin-positive interneurons was slightly decreased. Reduced corpus callosum thickness confirmed trend-level observations from in vivo MRI and voxel-wise tensor based morphometry. These neuroanatomical changes help explain functional phenotypes of this animal model, some of which resemble changes observed in human schizophrenia post mortem brain tissues. Our findings also demonstrate how a single molecular factor, DISC1 overexpression or misassembly, can account for a variety of seemingly unrelated morphological phenotypes and thus provides a possible unifying explanation for similar findings observed in sporadic schizophrenia patients. Our anatomical investigation of a defined model for sporadic mental illness enables a clearer definition of neuroanatomical changes associated with subsets of human sporadic schizophrenia. PMID:27721451

  17. Lower urogenital tract anatomical and functional phenotype in lysyl oxidase like-1 knockout mice resembles female pelvic floor dysfunction in humans.

    PubMed

    Lee, Una J; Gustilo-Ashby, A Marcus; Daneshgari, Firouz; Kuang, Mei; Vurbic, Drina; Lin, Dan Li; Flask, Chris A; Li, Tiansen; Damaser, Margot S

    2008-08-01

    Female pelvic floor dysfunction (FPFD) is a complex group of conditions that include urinary incontinence and pelvic organ prolapse (POP). In humans, elastin homeostasis has been implicated in the pathophysiology of FPFD. Lysyl oxidase-like 1 knockout (LOXL1-KO) mice demonstrate abnormal elastic fiber homeostasis and develop FPFD after parturition. We compared the lower urogenital tract (LUT) anatomy and function in LOXL1-KO mice with and without POP. LUT anatomy was assessed in LOXL1-KO mice over 28 wk. Pelvic visceral anatomy in LOXL1-KO was evaluated with a 7-Tesla magnetic resonance imaging (MRI) scanner. LUT function was assessed using conscious cystometry and leak point pressure (LPP) testing. Quantitative histological analysis of elastic fibers was performed on external urethral sphincter (EUS) cross sections. By 25 wk of age, 50% of parous LOXL1-KO mice developed POP. LOXL1-KO mice with POP had greater variability in the size and location of the bladder on MRI compared with mice without POP. Parity and POP were associated with lower LPP. Elastin clusters were significantly increased in the EUS of LOXL1-KO mice with POP. Because parity triggers POP in LOXL1-KO mice, LOXL1-KO mice with POP have variable internal pelvic anatomy, and both parity and POP are associated with a decrease in LPP, we conclude that LOXL1 LUT anatomical and functional phenotype resembles FPFD in humans. The increase in elastin clusters in the urethra of LOXL1-KO mice with POP suggests that elastin disorganization may lead to functional abnormalities. We conclude that LOXL1 warrants further investigation in the pathphysiology of FPFD.

  18. Human bronchial epithelial cells exposed in vitro to cigarette smoke at the air-liquid interface resemble bronchial epithelium from human smokers.

    PubMed

    Mathis, Carole; Poussin, Carine; Weisensee, Dirk; Gebel, Stephan; Hengstermann, Arnd; Sewer, Alain; Belcastro, Vincenzo; Xiang, Yang; Ansari, Sam; Wagner, Sandra; Hoeng, Julia; Peitsch, Manuel C

    2013-04-01

    Organotypic culture of human primary bronchial epithelial cells is a useful in vitro system to study normal biological processes and lung disease mechanisms, to develop new therapies, and to assess the biological perturbations induced by environmental pollutants. Herein, we investigate whether the perturbations induced by cigarette smoke (CS) and observed in the epithelium of smokers' airways are reproducible in this in vitro system (AIR-100 tissue), which has been shown to recapitulate most of the characteristics of the human bronchial epithelium. Human AIR-100 tissues were exposed to mainstream CS for 7, 14, 21, or 28 min at the air-liquid interface, and we investigated various biological endpoints [e.g., gene expression and microRNA profiles, matrix metalloproteinase 1 (MMP-1) release] at multiple postexposure time points (0.5, 2, 4, 24, 48 h). By performing a Gene Set Enrichment Analysis, we observed a significant enrichment of human smokers' bronchial epithelium gene signatures derived from different public transcriptomics datasets in CS-exposed AIR-100 tissue. Comparison of in vitro microRNA profiles with microRNA data from healthy smokers highlighted various highly translatable microRNAs associated with inflammation or with cell cycle processes that are known to be perturbed by CS in lung tissue. We also found a dose-dependent increase of MMP-1 release by AIR-100 tissue 48 h after CS exposure in agreement with the known effect of CS on this collagenase expression in smokers' tissues. In conclusion, a similar biological perturbation than the one observed in vivo in smokers' airway epithelium could be induced after a single CS exposure of a human organotypic bronchial epithelium-like tissue culture.

  19. Familial Resemblance for Loneliness

    PubMed Central

    Rebollo-Mesa, Irene; Abdellaoui, Abdel; Derom, Catherine A.; Willemsen, Gonneke; Cacioppo, John T.; Boomsma, Dorret I.

    2010-01-01

    Social isolation and loneliness in humans have been associated with physical and psychological morbidity, as well as mortality. This study aimed to assess the etiology of individual differences in feelings of loneliness. The genetic architecture of loneliness was explored in an extended twin-family design including 8,683 twins, siblings and parents from 3,911 families. In addition, 917 spouses of twins participated. The presence of assortative mating, genetic non-additivity, vertical cultural transmission, genotype–environment (GE) correlation and interaction was modeled. GE interaction was considered for several demographic characteristics. Results showed non-random mating for loneliness. We confirmed that loneliness is moderately heritable, with a significant contribution of non-additive genetic variation. There were no effects of vertical cultural transmission. With respect to demographic characteristics, results indicated that marriage, having offspring, more years of education, and a higher number of siblings are associated with lower levels of loneliness. Interestingly, these effects tended to be stronger for men than women. There was little evidence of changes in genetic architecture as a function of these characteristics. We conclude that the genetic architecture of loneliness points to non-additive genetic influences, suggesting it may be a trait that was not neutral to selection in our evolutionary past. Sociodemographic factors that influence the prevalence of loneliness do not affect its genetic architecture. PMID:20145989

  20. Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease

    PubMed Central

    Mattoso-Barbosa, Armanda Moreira; Perdigão-de-Oliveira, Marcelo; Costa, Ronaldo Peres; Elói-Santos, Silvana Maria; Gomes, Matheus de Souza; do Amaral, Laurence Rodrigues; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Dick, Edward J.; Hubbard, Gene B.; VandeBerg, Jane F.; VandeBerg, John L.

    2016-01-01

    Background Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations. Methods and Findings Our data established that CH displayed increased expression of CD32+ and CD56+ in monocytes and enhanced frequency of NK Granzyme A+ cells as compared to non-infected controls (NI). Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8+ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8+ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-γRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8+ T-cells, as the most reliable biomarkers of potential use for clinical applications. Conclusions Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease. PMID:26808481

  1. Sporadic meteoroid complex: Modeling

    NASA Astrophysics Data System (ADS)

    Andreev, V.

    2014-07-01

    The distribution of the sporadic meteoroids flux density over the celestial sphere is the common form of representation of the meteoroids distribution in the vicinity of the Earth's orbit. The determination of the flux density of sporadic meteor bodies is Q(V,e,f) = Q_0 P_e(V) P(e,f) where V is the meteoroid velocity, e,f are the radiant coordinates, Q_0 is the meteoroid flux over whole celestial sphere, P_e(V) is the conditional velocity distributions and P(e,f) is the radiant distribution over the celestial sphere. The sporadic meteoroid complex model is analytical and based on heliocentric velocities and radiant distributions. The multi-mode character of the heliocentric velocity and radiant distributions follows from the analysis of meteor observational data. This fact points to a complicated structure of the sporadic meteoroid complex. It is the consequence of the plurality of the parent bodies and the origin mechanisms of the meteoroids. The meteoroid complex was divided into four groups for that reason and with a goal of more accurate modelling of velocities and radiant distributions. As the classifying parameter to determine the meteoroid membership in any group, we adopt the Tisserand invariant relative to Jupiter T_J = 1/a + 2 A_J^{-3/2} √{a (1 - e^2)} cos i and the meteoroid orbit inclination i. Two meteoroid groups relate to long-period and short-period comets. One meteoroid group is related to asteroids. The relationship to the last, fourth group is a problematic one. Then, we construct models of radiant and velocity distributions for each group. The analytical model for the whole sporadic meteoroid complex is the sum of the ones for each group.

  2. Detection and characterization of Human caliciviruses associated with sporadic acute diarrhea in adults in Djibouti (horn of Africa).

    PubMed

    Maslin, Jérôme; Nicand, Elisabeth; Ambert-Balay, Katia; Fouet, Christine; Kaplon, Jérôme; Haus, Rachel; Pothier, Pierre; Kohli, Evelyne

    2008-03-01

    Recent advances in molecular diagnostics have allowed us to recognize Human caliciviruses (HuCVs) as important agents of acute diarrhea in industrialized countries. Their prevalence and genetic diversity in developing countries remains unknown. We report on the characterization of HuCVs among adults presenting acute diarrheas in Djibouti; 108 stool samples collected were screened by EIA, RTPCR, or cell cultures for the group A Rotaviruses, Adenoviruses, Astroviruses, and HuCVs, which were further characterized by genotyping. Among stool samples screened for HuCVs, 25.3% were positive. The other enteric viruses were less prevalent. The 11 HuCV strains sequenced revealed a large diversity (3 sapoviruses and 8 noroviruses). GII strains noroviruses were predominant, five were newly described genotypes, and two were recombinant with a pol gene related to GGIIb strains with the particularity to associate a unique pol gene to different capsid genes. These results could help to the knowledge of HuCV infections in Tropical Africa.

  3. Children's Explanations of Family Resemblances.

    ERIC Educational Resources Information Center

    Horobin, Karen D.

    Four studies investigated children's explanations for family resemblance and species-typical characteristics, under different conditions of biological parentage and rearing environment. Participating were 226 children between 3 and 11 years. Children Children were presented with a number of different tasks, some involving people and some domestic…

  4. Sporadic (nonepidemic) puerperal mastitis.

    PubMed

    Niebyl, J R; Spence, M R; Parmley, T H

    1978-02-01

    Sporadic puerperal mastitis is an acute cellulitis, characterized by fever and segmental erythema in the breast. Staphylococcus aureus can be cultured in approximately one-half of the cases. With early antibiotic therapy, the infection can be cleared and abscess formation prevented. Breast engorgement may also contribute to abscess formation, and so nursing should not be discontinued. No ill effects are observed in infants who continue to nurse. Twenty women with acute puerperal mastitis had breast milk cultures, and Staphylococcus aureus was recovered in seven cases. All patients were treated with antibiotics and continued nursing. No abscesses developed, and no ill effects were observed in any infants.

  5. Expression of catalytically active Matrix Metalloproteinase-1 in dermal fibroblasts induces collagen fragmentation and functional alterations that resemble aged human skin

    PubMed Central

    Xia, Wei; Hammerberg, Craig; Li, Yong; He, Tianyuan; Quan, Taihao; Voorhees, John J; Fisher, Gary J

    2013-01-01

    Summary Increased expression of matrix metalloproteinase-1 (MMP-1) and reduced production of type I collagen by dermal fibroblasts are prominent features of aged human skin. We have proposed that MMP-1-mediated collagen fibril fragmentation is a key driver of age-related decline of skin function. To investigate this hypothesis, we constructed, characterized, and expressed constitutively active MMP-1 mutant (MMP-1 V94G) in adult human skin in organ culture and fibroblasts in three dimensional collagen lattice cultures. Expression of MMP-1 V94G in young skin in organ culture caused fragmentation and ultrastructural alterations of collagen fibrils similar to those observed in aged human skin in vivo. Expression of MMP-1 V94G in dermal fibroblasts cultured in three-dimensional collagen lattices caused substantial collagen fragmentation, which was markedly reduced by MMP-1 siRNA-mediated knockdown or MMP inhibitor MMI270. Importantly, fibroblasts cultured in MMP-1 V94G-fragmented collagen lattices displayed many alterations observed in fibroblasts in aged human skin, including reduced cytoplasmic area, disassembled actin cytoskeleton, impaired TGF-β pathway, and reduced collagen production. These results support the concept that MMP-1-mediated fragmentation of dermal collagen fibrils alters the morphology and function of dermal fibroblasts, and provide a foundation for understanding specific mechanisms that link collagen fibril fragmentation to age-related decline of fibroblast function. PMID:23601157

  6. Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media

    PubMed Central

    Esteban-Rubio, Susana; Rackov, Gorjana; Rodríguez-Fanjul, Vanessa; Cruz, Jorge Oliver-De La; Prat-Acín, Ricardo; Peris-Celda, María; Blesa, David; Ramírez-Jiménez, Laura; Sánchez-Gómez, Pilar; Perona, Rosario; Escobedo-Lucea, Carmen; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

    2016-01-01

    Human gliomas harbour cancer stem cells (CSCs) that evolve along the course of the disease, forming highly heterogeneous subpopulations within the tumour mass. These cells possess self-renewal properties and appear to contribute to tumour initiation, metastasis and resistance to therapy. CSC cultures isolated from surgical samples are considered the best preclinical in vitro model for primary human gliomas. However, it is not yet well characterized to which extent their biological and functional properties change during in vitro passaging in the serum-free culture conditions. Here, we demonstrate that our CSC-enriched cultures harboured from one to several CSC clones from the human glioma sample. When xenotransplanted into mouse brain, these cells generated tumours that reproduced at least three different dissemination patterns found in original tumours. Along the passages in culture, CSCs displayed increased expression of stem cell markers, different ratios of chromosomal instability events, and a varied response to drug treatment. Our findings highlight the need for better characterization of CSC-enriched cultures in the context of their evolution in vitro, in order to uncover their full potential as preclinical models in the studies aimed at identifying molecular biomarkers and developing new therapeutic approaches of human gliomas. PMID:27589567

  7. Novel feline autoimmune blistering disease resembling bullous pemphigoid in humans: IgG autoantibodies target the NC16A ectodomain of type XVII collagen (BP180/BPAG2).

    PubMed

    Olivry, T; Chan, L S; Xu, L; Chace, P; Dunston, S M; Fahey, M; Marinkovich, M P

    1999-07-01

    In humans and dogs, bullous pemphigoid (BP) is an autoimmune blistering disease associated with the production of basement membrane autoantibodies that target the 180-kd type XVII collagen (BP180, BPAG2) and/or the 230-kd plakin epidermal isoform BPAG1e (BP230). In two adult cats, an acquired dermatosis and stomatitis was diagnosed as BP subsequent to the fulfillment of the following criteria: 1) presence of cutaneous vesicles, erosions, and ulcers; 2) histologic demonstration of subepidermal vesiculation with inflammatory cells, including eosinophils; 3) in vivo deposition of IgG autoantibodies at the epidermal basement membrane zone; and 4) serum IgG autoantibodies targeting a 180-kd epidermal protein identified as type XVII collagen. In both cats, the antigenic epitopes targeted by IgG autoantibodies were shown to be situated in the NC16A ectodomain of type XVII collagen, a situation similar to that of humans and dogs with BP. Feline BP therefore can be considered a clinical, histopathologic, and immunologic homologue of BP in humans and dogs.

  8. Detection and genetic characterization of porcine group A rotaviruses in asymptomatic pigs in smallholder farms in East Africa: predominance of P[8] genotype resembling human strains.

    PubMed

    Amimo, J O; Junga, J O; Ogara, W O; Vlasova, A N; Njahira, M N; Maina, S; Okoth, E A; Bishop, R P; Saif, L J; Djikeng, A

    2015-02-25

    Viral enteritis is a serious problem accounting for deaths in neonatal animals and humans worldwide. The absence of surveillance programs and diagnostic laboratory facilities have resulted in a lack of data on rotavirus associated diarrheas in pigs in East Africa. Here we describe the incidence of group A rotavirus (RVA) infections in asymptomatic young pigs in East Africa. Of the 446 samples examined, 26.2% (117/446) were positive for RVA. More nursing piglets (78.7%) shed RVA than weaned (32.9%) and grower (5.8%) pigs. RVA incidence was higher in pigs that were either housed_free-range (77.8%) or tethered_free-range (29.0%) than those that were free-range or housed or housed-tethered pigs. The farms with larger herd size (>10 pigs) had higher RVA prevalence (56.5%) than farms with smaller herd size (24.1-29.7%). This study revealed that age, management system and pig density significantly (p<0.01) influenced the incidence of RVA infections, with housed_free-range management system and larger herd size showing higher risks for RVA infection. Partial (811-1604nt region) sequence of the VP4 gene of selected positive samples revealed that different genotypes (P[6], P[8] and P[13]) are circulating in the study area with P[8] being predominant. The P[6] strain shared nucleotide (nt) and amino acid (aa) sequence identity of 84.4-91.3% and 95.1-96.9%, respectively, with known porcine and human P[6] strains. The P[8] strains shared high nt and aa sequence identity with known human P[8] strains ranging from 95.6-100% to 92-100%, respectively. The P[13] strains shared nt and aa sequence identity of 83.6-91.7% and 89.3-96.4%, respectively, only with known porcine P[13] strains. No P[8] strains yielded RNA of sufficient quality/quantity for full genome sequencing. However analysis of the full genome constellation of the P[6], two P[13] and one untypeable strains revealed that the P[6] strain (Ke-003-5) genome constellation was G26-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H1, P[13

  9. Mouse model of human RPE65 P25L hypomorph resembles wild type under normal light rearing but is fully resistant to acute light damage

    PubMed Central

    Li, Yan; Yu, Shirley; Duncan, Todd; Li, Yichao; Liu, Pinghu; Gene, Erelda; Cortes-Pena, Yoel; Qian, Haohua; Dong, Lijin; Redmond, T. Michael

    2015-01-01

    Human RPE65 mutations cause a spectrum of blinding retinal dystrophies from severe early-onset disease to milder manifestations. The RPE65 P25L missense mutation, though having <10% of wild-type (WT) activity, causes relatively mild retinal degeneration. To better understand these mild forms of RPE65-related retinal degeneration, and their effect on cone photoreceptor survival, we generated an Rpe65/P25L knock-in (KI/KI) mouse model. We found that, when subject to the low-light regime (∼100 lux) of regular mouse housing, homozygous Rpe65/P25L KI/KI mice are morphologically and functionally very similar to WT siblings. While mutant protein expression is decreased by over 80%, KI/KI mice retinae retain comparable 11-cis-retinal levels with WT. Consistently, the scotopic and photopic electroretinographic (ERG) responses to single-flash stimuli also show no difference between KI/KI and WT mice. However, the recovery of a-wave response following moderate visual pigment bleach is delayed in KI/KI mice. Importantly, KI/KI mice show significantly increased resistance to high-intensity (20 000 lux for 30 min) light-induced retinal damage (LIRD) as compared with WT, indicating impaired rhodopsin regeneration in KI/KI. Taken together, the Rpe65/P25L mutant produces sufficient chromophore under normal conditions to keep opsins replete and thus manifests a minimal phenotype. Only when exposed to intensive light is this hypomorphic mutation manifested physiologically, as its reduced expression and catalytic activity protects against the successive cycles of opsin regeneration underlying LIRD. These data also help define minimal requirements of chromophore for photoreceptor survival in vivo and may be useful in assessing a beneficial therapeutic dose for RPE65 gene therapy in humans. PMID:25972377

  10. Genetics Home Reference: sporadic hemiplegic migraine

    MedlinePlus

    ... Home Health Conditions sporadic hemiplegic migraine sporadic hemiplegic migraine Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Sporadic hemiplegic migraine is a rare form of migraine headache. Migraines ...

  11. In Vitro Development and Characterization of a Tissue-Engineered Conduit Resembling Esophageal Wall Using Human and Pig Skeletal Myoblast, Oral Epithelial Cells, and Biologic Scaffolds

    PubMed Central

    Poghosyan, Tigran; Gaujoux, Sebastien; Vanneaux, Valerie; Bruneval, Patrick; Domet, Thomas; Lecourt, Severine; Jarraya, Mohamed; Sfeir, Rony; Larghero, Jerome

    2013-01-01

    Introduction Tissue engineering represents a promising approach for esophageal replacement, considering the complexity and drawbacks of conventional techniques. Aim To create the components necessary to reconstruct in vitro or in vivo an esophageal wall, we analyzed the feasibility and the optimal conditions of human and pig skeletal myoblast (HSM and PSM) and porcine oral epithelial cell (OEC) culture on biologic scaffolds. Materials and Methods PSM and HSM were isolated from striated muscle and porcine OECs were extracted from oral mucosa biopsies. Myoblasts were seeded on an acellular scaffold issue from porcine small intestinal submucosa (SIS) and OEC on decellularized human amniotic membrane (HAM). Seeding conditions (cell concentrations [0.5×106 versus 106 cells/cm2] and culture periods [7, 14 and 21 days]), were analyzed using the methyl thiazoltetrazolium assay, quantitative PCR, flow cytometry, and immunohistochemistry. Results Phenotypic stability was observed after cellular expansion for PSM and HSM (85% and 97% CD56-positive cells, respectively), and OECs (90% AE1/AE3- positive cells). After PSM and HSM seeding, quantities of viable cells were similar whatever the initial cell concentration used and remained stable at all time points. During cell culture on SIS, a decrease of CD56-positive cells was observed (76% and 76% by D7, 56% and 70% by D14, 28% and 60% by D21, for PSM and HSM, respectively). Multilayered surface of α-actin smooth muscle and Desmine-positive cells organized in bundles was seen as soon as D7, with no evidence of cell within the SIS. Myoblasts fusion was observed at D21. Pax3 and Pax7 expression was downregulated and MyoD expression upregulated, at D14.OEC proliferation was observed on HAM with both cell concentrations from D7 to D21. The cell metabolism activity was more important on matrix seeded by 106 cells/cm2. With 0.5×106 OEC/cm2, a single layer of pancytokeratin-positive cells was seen at D7, which became pluristratified

  12. Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress) in Rats

    PubMed Central

    Abdul Aziz, Siti Hajar; Nordin, Massita; Ramasamy, Rajesh; Adam, Aishah

    2016-01-01

    This study attempts to develop an experimental gestational diabetes mellitus (GDM) animal model in female Sprague-Dawley rats. Rats were fed with high fat sucrose diet, impregnated, and induced with Streptozotocin and Nicotinamide on gestational day 0 (D0). Sleeping patterns of the rats were also manipulated to induce stress, a lifestyle factor that contributes to GDM. Rats were tested for glycemic parameters (glucose, C-peptide, and insulin), lipid profiles (total cholesterol, triglycerides, HDL, and LDL), genes affecting insulin signaling (IRS-2, AKT-1, and PCK-1), glucose transporters (GLUT-2 and GLUT-4), proinflammatory cytokines (IL-6, TNF-α), and antioxidants (SOD, CAT, and GPX) on D6 and D21. GDM rats showed possible insulin resistance as evidenced by high expression of proinflammatory cytokines, PCK-1 and CRP. Furthermore, low levels of IRS-2 and AKT-1 genes and downregulation of GLUT-4 from the initial to final phases indicate possible defect of insulin signaling. GDM rats also showed an impairment of antioxidant status and a hyperlipidemic state. Additionally, GDM rats exhibited significantly higher body weight and blood glucose and lower plasma insulin level and C-peptide than control. Based on the findings outlined, the current GDM animal model closely replicates the disease state in human and can serve as a reference for future investigations. PMID:27379252

  13. A majority of Ig H chain cDNA of normal human adult blood lymphocytes resembles cDNA for fetal Ig and natural autoantibodies

    SciTech Connect

    Huang, C.; Stollar, B.D. )

    1993-11-15

    Certain Ig V[sub H] gene segments, with few or no mutations, recur frequently in natural autoantibodies, fetal antibodies, and products of B cell tumors. The goal of this study was to determine whether similar Ig gene segment usage occurs in normal human adult PBL. Extending previous analyses, 105 randomly picked H chain V region clones of representative cDNA libraries from PBL were sequenced. Clones were from: IgM and IgG libraries from one RNA sample of a normal adult; a second IgM library from the same subject 11 mo later; and one IgM library from a second subject. Although some clones had clear evidence of mutation, 48 of 77 IgM clones (62%) shared 99% or more identity with known germline V[sub H] segments, and most of these had no mutations in the CDR3 portion of the J[sub H] segment. Certain V[sub H] gene segments, expressed in autoantibodies and fetal antibodies, occurred at high frequency in these libraries. Fourteen of the clones with 99% identity to known V[sub H] segments had CDR3 segments identical to portions of known germline D[sub H] gene sequences; two such clones had no N nucleotides at the V[sub H] D[sub H] or D[sub H]J[sub H] junctions. IgG-encoding sequences had more mutations than IgM-encoding sequences. J[sub H] and D[sub H] usage was not random. The circulating B cell population may represent a distinct compartment, with a large proportion of cells similar to those of the fetal and natural autoantibody repertoire. Polyreactive Ig products of these circulating cells may serve a screening function, binding and delivering diverse Ag to secondary lymphoid tissues where more highly selective antibodies are formed to foreign or Self-Ag. 40 refs., 2 figs., 6 tabs.

  14. Soluble human leukocyte antigen -G during pregnancy and infancy in Benin: Mother/child resemblance and association with the risk of malaria infection and low birth weight

    PubMed Central

    Milet, Jacqueline; Cottrell, Gilles; Mondière, Amandine; Avokpaho, Euripide; Gineau, Laure; Sabbagh, Audrey; Massougbodji, Achille; Moutairou, Kabirou; Donadi, Eduardo A.; Favier, Benoit; Carosella, Edgardo; Moreau, Philippe; Rouas-Freiss, Nathalie; Courtin, David; Garcia, André

    2017-01-01

    Human leukocyte antigen (HLA) G is a tolerogenic molecule involved in the maternal-fetal immune tolerance phenomenon. Its expression during some infectious diseases leading to immune evasion has been established. A first study conducted in Benin has shown that the production of soluble HLA-G (sHLA-G) during the first months of life is strongly correlated with the maternal level at delivery and associated with low birth weight and malaria. However sHLA-G measurements during pregnancy were not available for mothers and furthermore, to date the evolution of sHLA-G in pregnancy is not documented in African populations. To extend these previous findings, between January 2010 and June 2013, 400 pregnant women of a malaria preventive trial and their newborns were followed up in Benin until the age of 2 years. Soluble HLA-G was measured 3 times during pregnancy and repeatedly during the 2 years follow-up to explore how sHLA-G evolved and the factors associated. During pregnancy, plasma levels of sHLA-G remained stable and increased significantly at delivery (p<0.001). Multigravid women seemed to have the highest levels (p = 0.039). In infants, the level was highest in cord blood and decreased before stabilizing after 18 months (p<0.001). For children, a high level of sHLA-G was associated with malaria infection during the follow-up (p = 0.02) and low birth weight (p = 0.06). The mean level of sHLA-G during infancy was strongly correlated with the mother’s level during pregnancy (<0.001), and not only at delivery. Moreover, mothers with placental malaria infection had a higher probability of giving birth to a child with a high level of sHLA-g (p = 0.006). High sHLA-G levels during pregnancy might be associated with immune tolerance related to placental malaria. Further studies are needed but this study provides a first insight concerning the potential role of sHLA-G as a biomarker of weakness for newborns and infants. PMID:28166246

  15. DNA Methylation Identifies Loci Distinguishing Hereditary Nonpolyposis Colorectal Cancer Without Germ-Line MLH1/MSH2 Mutation from Sporadic Colorectal Cancer

    PubMed Central

    Chen, Chung-Hsing; Sheng Jiang, Shih; Hsieh, Ling-Ling; Tang, Reiping; Hsiung, Chao A; Tsai, Hui-Ju; Chang, I-Shou

    2016-01-01

    Objectives: Roughly half of hereditary nonpolyposis colorectal cancer (HNPCC) cases are Lynch syndrome and exhibit germ-line mutations in DNA mismatch repair (MMR) genes; the other half are familial colorectal cancer (CRC) type X (FCCTX) and are MMR proficient. About 70% of Lynch syndrome tumors have germ-line MLH1 or MSH2 mutations. The clinical presentation, histopathological features, and carcinogenesis of FCCTX resemble those of sporadic MMR-proficient colorectal tumors. It is of interest to obtain biomarkers that distinguish FCCTX from sporadic microsatellite stable (MSS) CRC, to develop preventive strategies. Methods: The tumors and adjacent normal tissues of 40 patients with HNPCC were assayed using the Illumina Infinium HumanMethylation27 (HM27) BeadChip to assess the DNA methylation level at about 27,000 loci. The germ-line mutation status of MLH1 and MSH2 and the microsatellite instability status in these patients were obtained. Genome-wide DNA methylation measurements of three groups of patients with general CRC were downloaded from public domain databases. Probes with DNA methylation levels that differed significantly between patients with sporadic MSS CRC and FCCTX were examined, to explore their potential as biomarkers. Results: We found that MSS HNPCC tumors were overwhelmingly hypomethylated compared with those from patient groups with other types of CRC, including germ-line MLH1/MSH2-mutated HNPCC and sporadic MSS CRC. Five gene-marker panels that exhibited a sensitivity of 100% and a specificity higher than 90% in both discovery and validation cohorts were proposed to distinguish MSS HNPCC tumors from sporadic MSS CRC. Conclusions: Our results warrant further investigation and validation. The loci identified here may become useful biomarkers for distinguishing between FCCTX and sporadic MSS CRC tumors. PMID:27977020

  16. SAND FLY SPECIES COMPOSITION (DIPTERA: PSYCHODIDAE: PHLEBOTOMINAE) IN THE MUNICIPALITY OF CANTAGALO , AN AREA WITH SPORADIC CASES OF HUMAN CUTANEOUS LEISHMANIASIS IN RIO DE JANEIRO STATE, BRAZIL

    PubMed Central

    PERES-DIAS, Quezia Nunes; OLIVEIRA, Claudete Diniz; de SOUZA, Marcos Barbosa; MEIRA, Antônio de Medeiros; VILLANOVA, Ciro Benigno

    2016-01-01

    SUMMARY The municipality of Cantagalo is an area with sustained transmission of American Cutaneous Leishmaniasis (ACL). Monthly sand fly collections were performed for three years (June 2012 - May 2015) using a CDC light trap. A total of 3,310 specimens belonging to 12 species were trapped: Nyssomyia intermedia, Nyssomyia whitmani, Migonemyia migonei, Evandromyia lenti, Evandromyia cortelezzii, Micropygomyia quinquefer, Brumptomyia brumpti, Psathyromyia aragaoi, Micropygomyia schreiberi, Pintomyia fischeri, Sciopemyia sordellii, and Evandromyia edwardsi. The last seven species have not been previously recorded in this area. The highest abundance of species occurred between October and March. October was the month with the highest number of captured sand flies, one month before the peak in the summer rainfall. In October the highest number of Ny. intermedia, Ny. whitmani and Mg. migonei, were also collected, the three epidemiologically most important species. The high abundance of species with epidemiological importance for ACL transmission might explain the sporadic occurrence of the disease in the area. PMID:27410910

  17. Midlatitude sporadic-E layers

    NASA Technical Reports Server (NTRS)

    Miller, K. L.; Smith, L. G.

    1976-01-01

    The partially transparent echo from midlatitude sporadic E layers was recorded by ionosondes between the blanketing frequency and the maximum frequency. The theory that the midlatitude sporadic E layers are not uniform in the horizontal plane but contain localized regions of high electron density was evaluated using data obtained by incoherent scatter radar and found to provide a satisfactory explanation. The main features of midlatitude sporadic E layers are consistent with the convergence of metallic ions as described by the wind shear theory applied to gravity waves and tides. The interference of gravity waves with other gravity waves and tides can be recognized in the altitudes of occurrence and the structure of the layers. Small scale horizontal irregularities are attributed in some cases to critical level effects and in others to fluid instabilities. The convergence of a meteor trail can, under some circumstances, account for localized enhancement of the electron density in the layer.

  18. The monster sporadic group and a theory underlying superstring models

    SciTech Connect

    Chapline, G.

    1996-09-01

    The pattern of duality symmetries acting on the states of compactified superstring models reinforces an earlier suggestion that the Monster sporadic group is a hidden symmetry for superstring models. This in turn points to a supersymmetric theory of self-dual and anti-self-dual K3 manifolds joined by Dirac strings and evolving in a 13 dimensional spacetime as the fundamental theory. In addition to the usual graviton and dilaton this theory contains matter-like degrees of freedom resembling the massless states of the heterotic string, thus providing a completely geometric interpretation for ordinary matter. 25 refs.

  19. Positive selection at codon 38 of the human KCNE1 (= minK) gene and sporadic absence of 38Ser-coding mRNAs in Gly38Ser heterozygotes

    PubMed Central

    Herlyn, Holger; Zechner, Ulrich; Oswald, Franz; Pfeufer, Arne; Zischler, Hans; Haaf, Thomas

    2009-01-01

    Background KCNE1 represents the regulatory beta-subunit of the slowly activating delayed rectifier potassium channel (IKs). Variants of KCNE1 have repeatedly been linked to the long-QT syndrome (LQTS), a disorder which predisposes to deafness, ventricular tachyarrhythmia, syncope, and sudden cardiac death. Results We here analyze the evolution of the common Gly38Ser variant (rs1805127), using genomic DNAs, complementary DNAs, and HEK293-expressed variants of altogether 19 mammalian species. The between species comparison reveals that the human-specific Gly38Ser polymorphism evolved under strong positive Darwinian selection, probably in adaptation to specific challenges in the fine-tuning of IKs channels. The involved amino acid exchanges (Asp > Gly, Gly > Ser) are moderately radical and do not induce apparent changes in posttranslational modification. According to population genetic analyses (HapMap phase II) a heterozygote advantage accounts for the maintenance of the Gly38Ser polymorphism in humans. On the other hand, the expression of the 38Ser allele seems to be disadvantageous under certain conditions, as suggested by the sporadic deficiency of 38Ser-coding mRNAs in heterozygote Central Europeans and the depletion of homozygotes 38Ser in the Yoruban sample. Conclusion We speculate that individual differences in genomic imprinting or genomic recoding might have contributed to conflicting results of recent association studies between Gly38Ser polymorphism and QT phenotype. The findings thus highlight the relevance of mRNA data in future association studies of genotypes and clinical disorders. To the best of our knowledge, they moreover provide first time evidence for a unique pattern; i.e. coincidence of positive Darwinian selection and polymorphism with a sporadically suppressed expression of one allele. PMID:19660109

  20. Sporadic ampullary hamartoma simulating cancer

    PubMed Central

    Moyana, Terence N.; Miller, Grant G.; Keith, Roger G.

    1997-01-01

    Ampullary tumours are uncommon. They may occur with familial polyposis syndromes or neurofibromatosis. It can be difficult to distinguish them from their periampullary counterparts on clinical, radiologic or histologic grounds. Because most ampullary and periampullary tumours are malignant, they tend to be treated by radical surgery. A 67-year-old man was seen with a sporadic ampullary hamartoma that simulated cancer. It was succesfully treated by local excision through a transverse duodenotomy. PMID:9194785

  1. Immune-privileged embryonic Swiss mouse STO and STO cell-derived progenitor cells: major histocompatibility complex and cell differentiation antigen expression patterns resemble those of human embryonic stem cell lines.

    PubMed

    Koch, Katherine S; Son, Kyung-Hwa; Maehr, Rene; Pellicciotta, Illenia; Ploegh, Hidde L; Zanetti, Maurizio; Sell, Stewart; Leffert, Hyam L

    2006-09-01

    Embryonic mouse STO (S, SIM; T, 6-thioguanine resistant; O, ouabain resistant) and 3(8)21-enhanced green fluorescent protein (EGFP) cell lines exhibit long-term survival and hepatic progenitor cell behaviour after xenogeneic engraftment in non-immunosuppressed inbred rats, and were previously designated major histocompatibility complex (MHC) class I- and class II-negative lines. To determine the molecular basis for undetectable MHC determinants, the expression and haplotype of H-2K, H-2D, H-2L and I-A proteins were reassessed by reverse transcriptase-polymerase chain reaction (RT-PCR), cDNA sequencing, RNA hybridization, immunoblotting, quantitative RT-PCR (QPCR), immunocytochemistry and flow cytometry. To detect cell differentiation (CD) surface antigens characteristic of stem cells, apoptotic regulation or adaptive immunity that might facilitate progenitor cell status or immune privilege, flow cytometry was also used to screen untreated and cytokine [interferon (IFN)-gamma]-treated cultures. Despite prior PCR genotyping analyses suggestive of H-2q haplotypes in STO, 3(8)21-EGFP and parental 3(8)21 cells, all three lines expressed H-2K cDNA sequences identical to those of d-haplotype BALB/c mice, as well as constitutive and cytokine-inducible H-2K(d) determinants. In contrast, apart from H-2L(d[LOW]) display in 3(8)21 cells, H-2Dd, H-2Ld and I-Ad determinants were undetectable. All three lines expressed constitutive and cytokine-inducible CD34; however, except for inducible CD117([LOW]) expression in 3(8)21 cells, no expression of CD45, CD117, CD62L, CD80, CD86, CD90.1 or CD95L/CD178 was observed. Constitutive and cytokine-inducible CD95([LOW]) expression was detected in STO and 3(8)21 cells, but not in 3(8)21-EGFP cells. MHC (class I(+[LOW])/class II-) and CD (CD34+/CD80-/CD86-/CD95L-) expression patterns in STO and STO cell-derived progenitor cells resemble patterns reported for human embryonic stem cell lines. Whether these patterns reflect associations with

  2. Sporadic medulloblastomas contain PTCH mutations.

    PubMed

    Raffel, C; Jenkins, R B; Frederick, L; Hebrink, D; Alderete, B; Fults, D W; James, C D

    1997-03-01

    Nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin's syndrome, is an autosomal dominant disorder that predisposes to developmental defects and various forms of cancer. PTCH was recently proposed as a candidate gene for NBCCS due to its frequent mutation in basal cell carcinomas, the cancer most often associated with this syndrome. Another NBCCS-associated cancer is medulloblastoma, a common central nervous system tumor in children. Most medulloblastomas, however, occur without indication of an inherited predisposition. We have examined 24 sporadic medulloblastomas for loss of heterozygosity (LOH) at loci flanking as well as within PTCH. In cases with LOH, single-strand conformational polymorphism and sequencing analysis were performed to determine the status of the remaining PTCH allele. Microsatellite analysis indicated LOH of PTCH in 5 of 24 tumors, and in three of these cases a mutation of the remaining allele was identified. Two of the mutations were duplication insertions, and the third consisted of a single base deletion. It is interesting that all three mutations occur in exon 17 of the PTCH gene. These data suggest that inactivation of PTCH function is involved in the development of at least a subset of sporadic medulloblastomas.

  3. Sporadic Fatal Insomnia in an Adolescent

    PubMed Central

    Blase, Jennifer L.; Cracco, Laura; Schonberger, Lawrence B.; Maddox, Ryan A.; Cohen, Yvonne; Cali, Ignazio

    2014-01-01

    The occurrence of sporadic prion disease among adolescents is extremely rare. A prion disease was confirmed in an adolescent with disease onset at 13 years of age. Genetic, neuropathologic, and biochemical analyses of the patient’s autopsy brain tissue were consistent with sporadic fatal insomnia, a type of sporadic prion disease. There was no evidence of an environmental source of infection, and this patient represents the youngest documented case of sporadic prion disease. Although rare, a prion disease diagnosis should not be discounted in adolescents exhibiting neurologic signs. Brain tissue testing is necessary for disease confirmation and is particularly beneficial in cases with an unusual clinical presentation. PMID:24488737

  4. Characterization of azoxymethane-induced colon tumor metastasis to lung in a mouse model relevant to human sporadic colorectal cancer and evaluation of grape seed extract efficacy.

    PubMed

    Derry, Molly M; Raina, Komal; Agarwal, Rajesh; Agarwal, Chapla

    2014-08-01

    The second leading cause of cancer-related deaths (both genders combined) in the United States is colorectal cancer (CRC). This emphasizes the need to develop both effective therapies for CRC patients and pre-clinical models mimicking human disease that carry translational potential in drug-development. Notably, at present there are no in situ models of CRC metastasis to lung. In our azoxymethane-induced colon tumorigenesis study in A/J mice assessing grape seed extract (GSE) efficacy, during necropsy we also found multiple lung nodules suggestive of colon tumor metastasis to lung that were significantly inhibited in GSE fed group. Both histopathological and molecular studies were performed to characterize and establish the origin of these lesions in lung. Histologically these nodules were determined as adenocarcinoma of mucin origin. Molecular analyses by immunohistochemistry (IHC) and RT-PCR revealed strong protein and transcript levels of colon specific markers CDX2 and CK20 in these lung nodules compared to uninvolved control lung tissue. Vis-à-vis, these nodules also showed minimally expressed lung specific biomarkers, specifically surfactant D and TTF-1, in IHC analysis. Additionally, 0.25% GSE supplementation in diet (w/w) decreased the incidence of these lung nodules by 53% and their total number by 66%. Together, the characterization of this unique in situ mouse model of CRC metastasis to lung provides translational opportunities in developing effective therapies to clinically manage and treat CRC at the advanced stage. Moreover, GSE efficacy in inhibiting CRC metastasis to lung in this model further supports its translational potential in controlling CRC growth, progression and metastasis in patients.

  5. A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1.

    PubMed

    Gach, Johannes S; Quendler, Heribert; Tong, Tommy; Narayan, Kristin M; Du, Sean X; Whalen, Robert G; Binley, James M; Forthal, Donald N; Poignard, Pascal; Zwick, Michael B

    2013-01-01

    Primary isolates of HIV-1 resist neutralization by most antibodies to the CD4 binding site (CD4bs) on gp120 due to occlusion of this site on the trimeric spike. We describe 1F7, a human CD4bs monoclonal antibody that was found to be exceptionally potent against the HIV-1 primary isolate JR-FL. However, 1F7 failed to neutralize a patient-matched primary isolate, JR-CSF even though the two isolates differ by <10% in gp120 at the protein level. In an HIV-1 cross clade panel (n = 157), 1F7 exhibited moderate breadth, but occasionally achieved considerable potency. In binding experiments using monomeric gp120s of select resistant isolates and domain-swap chimeras between JR-FL and JR-CSF, recognition by 1F7 was limited by sequence polymorphisms involving at least the C2 region of Env. Putative N-linked glycosylation site (PNGS) mutations, notably at position 197, allowed 1F7 to neutralize JR-CSF potently without improving binding to the cognate, monomeric gp120. In contrast, flow cytometry experiments using the same PNGS mutants revealed that 1F7 binding is enhanced on cognate trimeric Env. BN-PAGE mobility shift experiments revealed that 1F7 is sensitive to the diagnostic mutation D368R in the CD4 binding loop of gp120. Our data on 1F7 reinforce how exquisitely targeted CD4bs antibodies must be to achieve cross neutralization of two closely related primary isolates. High-resolution analyses of trimeric Env that show the orientation of glycans and polymorphic elements of the CD4bs that affect binding to antibodies like 1F7 are desirable to understand how to promote immunogenicity of more conserved elements of the CD4bs.

  6. Ig heavy chain third complementarity determining regions (H CDR3s) after stem cell transplantation do not resemble the developing human fetal H CDR3s in size distribution and Ig gene utilization.

    PubMed

    Gokmen, E; Raaphorst, F M; Boldt, D H; Teale, J M

    1998-10-15

    Previous studies have suggested that the B-cell repertoire after stem cell transplantation resembles the developing repertoire in the fetus. Fetal and adult repertoires differ strikingly at the molecular level in Ig heavy chain third complementarity determining region (H CDR3) size distribution and Ig gene utilization. Previously, the posttransplant repertoire has not been studied fully in this regard. In this study, we analyzed H CDR3s posttransplant using CDR3 fingerprinting, single-strand conformation polymorphism (SSCP), and random sequencing. Eleven adult patients who received either autologous (n = 6) or allogeneic adult sibling (n = 5) hematopoietic stem cell transplants were studied. IgM H CDR3 repertoires demonstrated limited clonal diversity within the first 6 to 10 weeks posttransplant. By 3 to 4 months, the IgM H CDR3 repertoires were as diverse as those in healthy adults. Reconstitution of the IgM diversity correlated with the expansion of the multimember VH3 family. By contrast, the contribution of the single-member VH6 family was limited in most patients up to 6 to 9 months. No evidence was seen for greater contribution of VH6 posttransplant. IgG repertoires remained clonally restricted at all times. In all patients, H CDR3 sizes fell within adult limits. Direct nucleotide sequencing of H CDR3s showed adult-type N-nucleotide insertions and Ig gene utilization. These results indicate that the emerging repertoire posttransplant does not resemble the developing fetal repertoire at the molecular level.

  7. Molecular pathogenesis of sporadic prion diseases in man.

    PubMed

    Safar, Jiri G

    2012-01-01

    The yeast, fungal and mammalian prions determine heritable and infectious traits that are encoded in alternative conformations of proteins. They cause lethal sporadic, familial and infectious neurodegenerative conditions in man, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, sporadic fatal insomnia (SFI) and likely variable protease-sensitive prionopathy (VPSPr). The most prevalent of human prion diseases is sporadic (s)CJD. Recent advances in amplification and detection of prions led to considerable optimism that early and possibly preclinical diagnosis and therapy might become a reality. Although several drugs have already been tested in small numbers of sCJD patients, there is no clear evidence of any agent's efficacy. Therefore, it remains crucial to determine the full spectrum of sCJD prion strains and the conformational features in the pathogenic human prion protein governing replication of sCJD prions. Research in this direction is essential for the rational development of diagnostic as well as therapeutic strategies. Moreover, there is growing recognition that fundamental processes involved in human prion propagation - intercellular induction of protein misfolding and seeded aggregation of misfolded host proteins - are of far wider significance. This insight leads to new avenues of research in the ever-widening spectrum of age-related human neurodegenerative diseases that are caused by protein misfolding and that pose a major challenge for healthcare.

  8. Darwinian Behavior in a Cold, Sporadically Fed Pool of Ribonucleotides

    PubMed Central

    2012-01-01

    Abstract A testable, explicit origin for Darwinian behavior, feasible on a chaotic early Earth, would aid origins discussion. Here I show that a pool receiving unreliable supplies of unstable ribonucleotide precursors can recurrently fill this role. By using numerical integration, the differential equations governing a sporadically fed pool are solved, yielding quantitative constraints for the proliferation of molecules that also have a chemical phenotype. For example, templated triphosphate nucleotide joining is >104 too slow, suggesting that a group more reactive than pyrophosphate activated primordial nucleotides. However, measured literature rates are sufficient if the Initial Darwinian Ancestor (IDA) resembles a 5′-5′ cofactor-like dinucleotide RNA, synthesized via activation with a phosphorimidazolide-like group. A sporadically fed pool offers unforeseen advantages; for example, the pool hosts a novel replicator which is predominantly unpaired, even though it replicates. Such free template is optimized for effective selection during its replication. Pool nucleotides are also subject to a broadly based selection that impels the population toward replication, effective selection, and Darwinian behavior. Such a primordial pool may have left detectable modern traces. A sporadically fed ribonucleotide pool also fits a recognizable early Earth environment, has recognizable modern descendants, and suits the early shape of the phylogenetic tree of Earthly life. Finally, analysis points to particular data now needed to refine the hypothesis. Accordingly, a kinetically explicit chemical hypothesis for a terran IDA can be justified, and informative experiments seem readily accessible. Key Words: Cofactor—RNA—Origin of life—Replication—Initial Darwinian Ancestor (IDA). Astrobiology 12, 870–883. PMID:22946838

  9. [Three sporadic cases of acute hepatitis E].

    PubMed

    Kim, Dong Han; Park, Hyeuk; Moon, Seung Won; Jeong, Jong Hyuk; Yang, Hyuk Seung; Kim, Do Hyun; Kim, Ho Dong

    2007-08-01

    Acute hepatitis E is an endemic disease, commonly reported in Indian subcontinent, China, Africa, Central America, and so forth. It is a self-limiting disease like other acute hepatitis except in pregnant patient. Although sporadic hepatitis E is noted all over the world, most of them are associated with travel history to HEV-endemic area. In Korea, Hepatitis E is rarely reported. Moreover, sporadic acute hepatitis E without travel history to HEV-endemic area is very rare. We experienced three sporadic cases of acute hepatitis E, without travel history. All of them presented acute hepatitis symptoms, elevated aminotransferase, and positive IgM HEV Ab. Symptoms and aminotransferase levels were normalized during hospitalization and IgM HEV Ab converted negative after 4-8 months. We report three sporadic cases of onset-acute hepatitis E without travel history to HEV-endemic area.

  10. Sporadic-E As Observed with Rockets

    NASA Technical Reports Server (NTRS)

    Seddon, J. Carl

    1961-01-01

    Data obtained with rockets flown over New Mexico, U.S.A. and Manitoba, Canada have always shown the sporadic-E layer to be a thin layer with a large electron density gradient. The vertical electron density profiles and the horizontal uniformity of the sporadic-E layer are discussed herein. These layers have a strong tendency to form at preferential altitudes separated by approximately 6 km, and a striking correlation exists with wind- shears and magnetic field variations. In two cases where comparisons with ionograms were possible, the minimum frequency of the F-region echoes was found approximately equal to the plasma frequency of the sporadic-E layer reduced by half the gyrofrequency. On the other hand, the maximum frequency of the sporadic-E echoes as noted on ionograms was sometimes as much as 1 to 2 Mc greater than the plasma frequency.

  11. Acute Sporadic Hepatitis in Sudanese Children

    DTIC Science & Technology

    1991-01-01

    potential risk factors of hepatitis transmission dur- hepatitis in children in this area, as well as a ing the 6 months prior to the onset of symptoms...1987aI. In the present study, the causes and risk Accepted for publication September 5. 1990. factors of acute sporadic hepatitis in Sudanese children ...ELEMENT NO. NO. NO. ACCESSION NO. N.A. 11. TITLE (include Security Cassification) Acute sporadic hepatitis in Sudanese children 12. PERSONAL AUTHOR(S

  12. Frequent alteration of the tumor suppressor gene APC in sporadic canine colorectal tumors.

    PubMed

    Youmans, Lydia; Taylor, Cynthia; Shin, Edwin; Harrell, Adrienne; Ellis, Angela E; Séguin, Bernard; Ji, Xinglai; Zhao, Shaying

    2012-01-01

    Sporadic canine colorectal cancers (CRCs) should make excellent models for studying the corresponding human cancers. To molecularly characterize canine CRC, we investigated exonic sequence mutations of adenomatous polyposis coli (APC), the best known tumor suppressor gene of human CRC, in 23 sporadic canine colorectal tumors, including 8 adenomas and 15 adenocarcinomas, via exon-resequencing analysis. As a comparison, we also performed the same sequencing analysis on 10 other genes, either located at human 5q22 (the same locus as APC) or 18q21 (also frequently altered in human CRC), or known to play a role in human carcinogenesis. We noted that APC was the most significantly mutated gene in both canine adenomas and adenocarcinomas among the 11 genes examined. Significantly, we detected large deletions of ≥ 10 bases, many clustered near the mutation cluster region, as well as single or two base deletions in ~70% canine tumors of both subtypes. These observations indicate that like in the human, APC is also frequently altered in sporadic colorectal tumors in the dog and its alteration is an early event in canine colorectal tumorigenesis. Our study provides further evidence demonstrating the molecular similarity in pathogenesis between sporadic human and canine CRCs. This work, along with our previous copy number abnormality study, supports that sporadic canine CRCs are valid models of human CRCs at the molecular level.

  13. Neuroanatomy and pathology of sporadic Parkinson's disease.

    PubMed

    Braak, Heiko; Del Tredici, Kelly

    2009-01-01

    The proteinopathy sporadic Parkinson's disease (sPD) is the second most frequent degenerative disorder of the human nervous system after Alzheimer's disease. The alpha-synuclein inclusion body pathology (Lewy pathology) associated with sPD is distributed throughout the central, peripheral, and enteric nervous systems. The resulting nonrandom neuronal dysfunction and, in some regions, neuronal loss is reflected in a topographic distribution pattern of the Lewy pathology that, in the brain, can be staged. Except for olfactory structures and spinal cord constituents of the pain system, sensory components of the nervous system remain uninvolved or virtually intact. The most disease-related damage revolves around motor areas--particularly around superordinate centers of the limbic and visceromotor systems as well as portions of the somatomotor system. Vulnerable regions are interconnected anatomically and susceptible nerve cell types are not neurotransmitter-dependent. Not all clinical symptoms emerging in the course of sPD can be explained by a lack of dopamine in the nigrostriatal system. These include autonomic dysfunction, pain, hyposmia or anosmia, excessive daytime sleepiness, rapid eye movement (REM) sleep behavioral disorder, depression, anxiety, cognitive decline, and dementia. Against the background of the normal morphology and anatomy, the authors analyze the pathoanatomy of sPD in the nervous system at various neuropathological stages and summarize the potential functional consequences of the lesions.

  14. MAJOR MOLECULAR GENETIC DRIVERS IN SPORADIC PRIMARY HYPERPARATHYROIDISM

    PubMed Central

    ARNOLD, ANDREW

    2016-01-01

    Primary hyperparathyroidism is primarily due to a solitary parathyroid adenoma but multi-gland disease, parathyroid carcinoma, and ectopic parathyroid hormone production can occur. Although primary hyperparathyroidism mostly presents sporadically, strong familial predispositions also exist. Much is known about heritable genetic mutations responsible for these syndromes, including multiple endocrine neoplasia types 1 and 2A, hyperparathyroidism-jaw tumor syndrome, and familial hypocalciuric hypercalcemia. Acquired mutations in common sporadic hyperparathyroidism have also been discovered. Here we focus on the most common and well-established genetic drivers: 1) involvement of the oncogene cyclin D1 in human neoplasia was first established in parathyroid adenomas, followed by recognition of its importance in other tumor types including breast cancer and B-lymphoid malignancy; and 2) somatic mutation of the MEN1 gene, first identified as the source of pathogenic germline mutations in patients with familial endocrinopathies, is found in a substantial fraction of non-familial parathyroid adenomas. PMID:28066056

  15. The cybrid model of sporadic Parkinson's disease.

    PubMed

    Trimmer, Patricia A; Bennett, James P

    2009-08-01

    Parkinson's disease (PD) is the eponym attached to the most prevalent neurodegenerative movement disorder of adults, derived from observations of an early nineteenth century physician and paleontologist, James Parkinson, and is now recognized to encompass much more than a movement disorder clinically or dopamine neuron death pathologically. Most PD ( approximately 90%) is sporadic (sPD), is associated with mitochondrial deficiencies and has been studied in cell and animal models arising from the use of mitochondrial toxins that unfortunately have not predicted clinical efficacy to slow disease progression in humans. We have extensively studied the cytoplasmic hybrid ("cybrid") model of sPD in which donor mtDNAs are introduced into and expressed in neural tumor cells with identical nuclear genetic and environmental backgrounds. sPD cybrids demonstrate many abnormalities in which increased oxidative stress drives downstream antioxidant response and cell death activating signaling pathways. sPD cybrids regulate mitochondrial ETC genes and gene ontology families like sPD brain. sPD cybrids spontaneously form Lewy bodies and Lewy neurites, linking mtDNA expression to neuropathology, and demonstrate impaired organelle transport in processes and reduced mitochondrial respiration. Our recent studies show that near-infrared laser light therapy normalizes mitochondrial movement and can stimulate respiration in sPD cybrid neurons, and mitochondrial gene therapy can restore respiration and stimulate mitochondrial ETC gene and protein expression. sPD cybrids have provided multiple lines of circumstantial evidence linking mtDNA to sPD pathogenesis and can serve as platforms for therapy development. sPD cybrid models can be improved by the use of non-tumor human stem cell-derived neural precursor cells and by an introduction of postmortem brain mtDNA to test its causality directly.

  16. Body elimination attitude family resemblance in Kuwait.

    PubMed

    Al-Fayez, Ghenaim; Awadalla, Abdelwahid; Arikawa, Hiroko; Templer, Donald I; Hutton, Shane

    2009-12-01

    The purpose of the present study was to determine the family resemblance of attitude toward body elimination in Kuwaiti participants. This study was conceptualized in the context of the theories of moral development, importance of cleanliness in the Muslim religion, cross-cultural differences in personal hygiene practices, previous research reporting an association between family attitudes and body elimination attitude, and health implications. The 24-item Likert-type format Body Elimination Attitude Scale-Revised was administered to 277 Kuwaiti high school students and 437 of their parents. Females scored higher, indicating greater disgust, than the males. Moreover, sons' body elimination attitude correlated more strongly with fathers' attitude (r = .85) than with that of the mothers (r = .64). Daughters' attitude was similarly associated with the fathers' (r = .89) and the mothers' attitude (r = .86). The high correlations were discussed within the context of Kuwait having a collectivistic culture with authoritarian parenting style. The higher adolescent correlations, and in particular the boys' correlation with fathers than with mothers, was explained in terms of the more dominant role of the Muslim father in the family. Public health and future research implications were suggested. A theoretical formulation was advanced in which "ideal" body elimination attitude is relative rather than absolute, and is a function of one's life circumstances, one's occupation, one's culture and subculture, and the society that one lives in.

  17. Sporadically Emitting Pulsars at Low Frequencies

    NASA Astrophysics Data System (ADS)

    Meyers, B. W.; Tremblay, S. E.; Bhat, N. D. R.; Shannon, R. M.

    2017-01-01

    Sporadic emission from pulsars has long been observed, however, the mechanism which causes the intermittency is still a mystery. The proposed observations of three nulling pulsars (J0659+1414, J2048-1616 and J1456-6843), two Rotating Radio Transients (J0410-31 and J1423-56) and one intermittent pulsar (J1107-5907) will provide information on pulsar emission over a variety of time scales. Studying these objects at low frequencies allows us to explore the links between the different populations and how the sporadic emission evolves with frequency. Ultimately, studying these extraordinary pulsars gives us new insight into the dynamic nature of the emission processes and pulsar magnetosphere. This information is imperative for linking models and theories regarding pulsar radio emission physics to the myriad sporadic emission phenomena we observe.

  18. Disseminated cutaneous leishmaniasis resembling post-kala-azar dermal leishmaniasis caused by Leishmania donovani in three patients co-infected with visceral leishmaniasis and human immunodeficiency virus/acquired immunodeficiency syndrome in Ethiopia.

    PubMed

    Gelanew, Tesfaye; Hurissa, Zewdu; Diro, Ermias; Kassahun, Aysheshm; Kuhls, Katrin; Schönian, Gabriele; Hailu, Asrat

    2011-06-01

    We report paired strains of Leishmania parasites, one from the viscera and the other from skin lesions that were isolated from three patients with visceral leishmaniasis and disseminated cutaneous leishmaniasis that were co-infected with human immunodeficiency virus. The causative parasites were characterized by polymerase chain reaction-restriction length polymorphism of the ribosomal DNA internal transcribed spacer 1 and by a panel of multilocus microsatellite markers. We demonstrated that the causative agent was Leishmania donovani in all cases, irrespective of the phenotype of the disease. The paired strains from viscera and skin lesions of the same patients showed genetic identity across the 14 microsatellite markers investigated. These findings demonstrate that the skin lesions in these human immunodeficiency virus-positive patients with visceral leishmaniasis were caused by dissemination of viscerotropic L. donovani parasites as a consequence of severe immunosuppression. However, in all three patients, rapid clearance of the skin lesions was observed after antimonial therapy.

  19. The prion protein preference of sporadic Creutzfeldt-Jakob disease subtypes.

    PubMed

    Klemm, Helen M J; Welton, Jeremy M; Masters, Colin L; Klug, Genevieve M; Boyd, Alison; Hill, Andrew F; Collins, Steven J; Lawson, Victoria A

    2012-10-19

    Sporadic Creutzfeldt-Jakob disease (CJD) is the most prevalent manifestation of the transmissible spongiform encephalopathies or prion diseases affecting humans. The disease encompasses a spectrum of clinical phenotypes that have been correlated with molecular subtypes that are characterized by the molecular mass of the protease-resistant fragment of the disease-related conformation of the prion protein and a polymorphism at codon 129 of the gene encoding the prion protein. A cell-free assay of prion protein misfolding was used to investigate the ability of these sporadic CJD molecular subtypes to propagate using brain-derived sources of the cellular prion protein (PrP(C)). This study confirmed the presence of three distinct sporadic CJD molecular subtypes with PrP(C) substrate requirements that reflected their codon 129 associations in vivo. However, the ability of a sporadic CJD molecular subtype to use a specific PrP(C) substrate was not determined solely by codon 129 as the efficiency of prion propagation was also influenced by the composition of the brain tissue from which the PrP(C) substrate was sourced, thus indicating that nuances in PrP(C) or additional factors may determine sporadic CJD subtype. The results of this study will aid in the design of diagnostic assays that can detect prion disease across the diversity of sporadic CJD subtypes.

  20. Genetic Insights into Sporadic Parkinson's Disease Pathogenesis

    PubMed Central

    Chai, Chou; Lim, Kah-Leong

    2013-01-01

    Intensive research over the last 15 years has led to the identification of several autosomal recessive and dominant genes that cause familial Parkinson’s disease (PD). Importantly, the functional characterization of these genes has shed considerable insights into the molecular mechanisms underlying the etiology and pathogenesis of PD. Collectively; these studies implicate aberrant protein and mitochondrial homeostasis as key contributors to the development of PD, with oxidative stress likely acting as an important nexus between the two pathogenic events. Interestingly, recent genome-wide association studies (GWAS) have revealed variations in at least two of the identified familial PD genes (i.e. α-synuclein and LRRK2) as significant risk factors for the development of sporadic PD. At the same time, the studies also uncovered variability in novel alleles that is associated with increased risk for the disease. Additionally, in-silico meta-analyses of GWAS data have allowed major steps into the investigation of the roles of gene-gene and gene-environment interactions in sporadic PD. The emergent picture from the progress made thus far is that the etiology of sporadic PD is multi-factorial and presumably involves a complex interplay between a multitude of gene networks and the environment. Nonetheless, the biochemical pathways underlying familial and sporadic forms of PD are likely to be shared. PMID:24532982

  1. On the variability of sporadic E

    SciTech Connect

    Paul, A.K. )

    1990-02-01

    The analysis of digital ionograms taken in short-time intervals shows rapid changes of sporadic E parameters. This is directly visible in the variation of the top frequency or maximum electron density of such layers. Angle of arrival data which were available with those ionograms also showed fast changes of the apparent direction and often large deviations from vertical propagation. 5 refs.

  2. Models of sporadic meteor body distributions

    NASA Technical Reports Server (NTRS)

    Andreev, V. V.; Belkovich, O. I.

    1987-01-01

    The distribution of orbital elements and flux density over the celestial sphere are the most common forms of representation of the meteor body distribution in the vicinity of the Earth's orbit. The determination of flux density distribution of sporadic meteor bodies was worked out. The method and its results are discussed.

  3. Application of quantitative DTI metrics in sporadic CJD.

    PubMed

    Caverzasi, E; Henry, R G; Vitali, P; Lobach, I V; Kornak, J; Bastianello, S; Dearmond, S J; Miller, B L; Rosen, H J; Mandelli, M L; Geschwind, M D

    2014-01-01

    Diffusion Weighted Imaging is extremely important for the diagnosis of probable sporadic Jakob-Creutzfeldt disease, the most common human prion disease. Although visual assessment of DWI MRI is critical diagnostically, a more objective, quantifiable approach might more precisely identify the precise pattern of brain involvement. Furthermore, a quantitative, systematic tracking of MRI changes occurring over time might provide insights regarding the underlying histopathological mechanisms of human prion disease and provide information useful for clinical trials. The purposes of this study were: 1) to describe quantitatively the average cross-sectional pattern of reduced mean diffusivity, fractional anisotropy, atrophy and T1 relaxation in the gray matter (GM) in sporadic Jakob-Creutzfeldt disease, 2) to study changes in mean diffusivity and atrophy over time and 3) to explore their relationship with clinical scales. Twenty-six sporadic Jakob-Creutzfeldt disease and nine control subjects had MRIs on the same scanner; seven sCJD subjects had a second scan after approximately two months. Cortical and subcortical gray matter regions were parcellated with Freesurfer. Average cortical thickness (or subcortical volume), T1-relaxiation and mean diffusivity from co-registered diffusion maps were calculated in each region for each subject. Quantitatively on cross-sectional analysis, certain brain regions were preferentially affected by reduced mean diffusivity (parietal, temporal lobes, posterior cingulate, thalamus and deep nuclei), but with relative sparing of the frontal and occipital lobes. Serial imaging, surprisingly showed that mean diffusivity did not have a linear or unidirectional reduction over time, but tended to decrease initially and then reverse and increase towards normalization. Furthermore, there was a strong correlation between worsening of patient clinical function (based on modified Barthel score) and increasing mean diffusivity.

  4. Application of quantitative DTI metrics in sporadic CJD☆

    PubMed Central

    Caverzasi, E.; Henry, R.G.; Vitali, P.; Lobach, I.V.; Kornak, J.; Bastianello, S.; DeArmond, S.J.; Miller, B.L.; Rosen, H.J.; Mandelli, M.L.; Geschwind, M.D.

    2014-01-01

    Diffusion Weighted Imaging is extremely important for the diagnosis of probable sporadic Jakob–Creutzfeldt disease, the most common human prion disease. Although visual assessment of DWI MRI is critical diagnostically, a more objective, quantifiable approach might more precisely identify the precise pattern of brain involvement. Furthermore, a quantitative, systematic tracking of MRI changes occurring over time might provide insights regarding the underlying histopathological mechanisms of human prion disease and provide information useful for clinical trials. The purposes of this study were: 1) to describe quantitatively the average cross-sectional pattern of reduced mean diffusivity, fractional anisotropy, atrophy and T1 relaxation in the gray matter (GM) in sporadic Jakob–Creutzfeldt disease, 2) to study changes in mean diffusivity and atrophy over time and 3) to explore their relationship with clinical scales. Twenty-six sporadic Jakob–Creutzfeldt disease and nine control subjects had MRIs on the same scanner; seven sCJD subjects had a second scan after approximately two months. Cortical and subcortical gray matter regions were parcellated with Freesurfer. Average cortical thickness (or subcortical volume), T1-relaxiation and mean diffusivity from co-registered diffusion maps were calculated in each region for each subject. Quantitatively on cross-sectional analysis, certain brain regions were preferentially affected by reduced mean diffusivity (parietal, temporal lobes, posterior cingulate, thalamus and deep nuclei), but with relative sparing of the frontal and occipital lobes. Serial imaging, surprisingly showed that mean diffusivity did not have a linear or unidirectional reduction over time, but tended to decrease initially and then reverse and increase towards normalization. Furthermore, there was a strong correlation between worsening of patient clinical function (based on modified Barthel score) and increasing mean diffusivity. PMID:24624328

  5. On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy and Creutzfeldt-Jakob Disease

    PubMed Central

    McShane, Lisa M.; Zanusso, Gianluigi; Detwiler, Linda

    2006-01-01

    Strategies to investigate the possible existence of sporadic bovine spongiform encephalopathy (BSE) require systematic testing programs to identify cases in countries considered to have little or no risk of orally acquired disease or to detect a stable occurrence of atypical cases in countries in which orally acquired disease is disappearing. To achieve 95% statistical confidence that the prevalence for sporadic BSE is no greater than 1 per million (i.e., the annual incidence of sporadic Creutzfeldt-Jakob disease [CJD] in humans) would require negative tests in 3 million randomly selected older cattle. A link between BSE and sporadic CJD has been suggested on the basis of laboratory studies but is unsupported by epidemiologic observation. Such a link might yet be established by the discovery of a specific molecular marker or of particular combinations of trends over time of typical and atypical BSE and various subtypes of sporadic CJD, as their numbers are influenced by a continuation of current public health measures that exclude high-risk bovine tissues from the animal and human food chains. PMID:17326930

  6. BIN1 Is Decreased in Sporadic but Not Familial Alzheimer’s Disease or in Aging

    PubMed Central

    Glennon, Elizabeth B. C.; Whitehouse, Isobel J.; Miners, J. Scott; Kehoe, Patrick G.; Love, Seth; Kellett, Katherine A. B.; Hooper, Nigel M.

    2013-01-01

    Bridging integrator 1 (BIN1) has been implicated in sporadic Alzheimer’s disease (AD) by a number of genome wide association studies (GWAS) in a variety of populations. Here we measured BIN1 in frontal cortex samples from 24 sporadic AD and 24 age-matched non-dementia brains and correlated the expression of this protein with markers of AD. BIN1 was reduced by 87% (p=0.007) in sporadic AD compared to non-dementia controls, but BIN1 in sporadic AD did not correlate with soluble Aβ (rs=-0.084, p=0.698), insoluble Aβ (rs=0.237, p=0.269), Aβ plaque load (rs=0.063, p=0.771) or phospho-tau load (rs=-0.160, p=0.489). In contrast to our findings in sporadic AD, BIN1 was unchanged in the hippocampus from 6 cases of familial AD compared to 6 age-matched controls (p=0.488). BIN1 declined with age in a cohort of non-dementia control cases between 25 and 88 years but the correlation was not significant (rs=-0.449, p=0.081). Although BIN1 is known to have a role in endocytosis, and the processing of the amyloid precursor protein (APP) to form amyloid-β (Aβ) peptides is dependent on endocytosis, knockdown of BIN1 by targeted siRNA or the overexpression of BIN1 in a human neuroblastoma cell line (SH-SY5Y) had no effect on APP processing. These data suggest that the alteration in BIN1 is involved in the pathogenesis of sporadic, but not familial AD and is not a consequence of AD neurodegeneration or the ageing process, a finding in keeping with the numerous GWAS that implicate BIN1 in sporadic AD. However, the mechanism of its contribution remains to be established. PMID:24205320

  7. Comparison Between Sporadic and Misdiagnosed Sporadic Creutzfeldt-Jakob Disease: A Report of Two Cases.

    PubMed

    Zhao, Xiongfei; Yu, Yingxin; Zhao, Zhiru; Xu, Jiaping

    2015-06-01

    Definite accurate diagnosis for Creutzfeldt-Jakob disease (CJD) depends on neuropathologic examination of brain biopsy or autopsy. However, transmissible nature makes the invasive examination dangerous. This study was set to determine that the clinical features are for the diagnosis of CJD through a comparison study. We compared clinical features of two cases with initial diagnosis of sporadic CJD. One case was finally diagnosed as definite sporadic CJD. According to World Health Organization diagnosis criteria, the other one, which had been diagnosed as probable sporadic CJD, was confirmed as limbic encephalitis after long-term follow-up. Compared with the case of definite sporadic CJD, the misdiagnosed case did not present typical electroencephalogram (EEG) and diffusion-weighted in magnetic resonance images (DWI) of CJD. However, cerebrospinal fluid in the misdiagnosed patient showed 14-3-3 protein positivity. The patient conditions improved after treatment. Through this case comparison, we conclude that EEG and DWI are necessary for accurate diagnosis of sporadic CJD. Further, long-term follow-up is crucial to diagnosis and treatment of CJD.

  8. The NF1 gene: a frequent mutational target in sporadic pheochromocytomas and beyond.

    PubMed

    Welander, Jenny; Söderkvist, Peter; Gimm, Oliver

    2013-08-01

    Patients suffering from the neurofibromatosis type 1 syndrome, which is caused by germline mutations in the NF1 gene, have a tiny but not negligible risk of developing pheochromocytomas. It is, therefore, of interest that the NF1 gene has recently been revealed to carry somatic, inactivating mutations in a total of 35 (21.7%) of 161 sporadic pheochromocytomas in two independent tumor series. A majority of the tumors in both studies displayed loss of heterozygosity at the NF1 locus and a low NF1 mRNA expression. In view of previous findings that many sporadic pheochromocytomas cluster with neurofibromatosis type 1 syndrome-associated pheochromocytomas instead of forming clusters of their own, NF1 inactivation appears to be an important step in the pathogenesis of a large number of sporadic pheochromocytomas. A literature and public mutation database review has revealed that pheochromocytomas are among those human neoplasms in which somatic NF1 alterations are most frequent.

  9. Dynamical Model for the Toroidal Sporadic Meteors

    NASA Astrophysics Data System (ADS)

    Pokorný, Petr; Vokrouhlický, David; Nesvorný, David; Campbell-Brown, Margaret; Brown, Peter

    2014-07-01

    More than a decade of radar operations by the Canadian Meteor Orbit Radar have allowed both young and moderately old streams to be distinguished from the dispersed sporadic background component. The latter has been categorized according to broad radiant regions visible to Earth-based observers into three broad classes: the helion and anti-helion source, the north and south apex sources, and the north and south toroidal sources (and a related arc structure). The first two are populated mainly by dust released from Jupiter-family comets and new comets. Proper modeling of the toroidal sources has not to date been accomplished. Here, we develop a steady-state model for the toroidal source of the sporadic meteoroid complex, compare our model with the available radar measurements, and investigate a contribution of dust particles from our model to the whole population of sporadic meteoroids. We find that the long-term stable part of the toroidal particles is mainly fed by dust released by Halley type (long period) comets (HTCs). Our synthetic model reproduces most of the observed features of the toroidal particles, including the most troublesome low-eccentricity component, which is due to a combination of two effects: particles' ability to decouple from Jupiter and circularize by the Poynting-Robertson effect, and large collision probability for orbits similar to that of the Earth. Our calibrated model also allows us to estimate the total mass of the HTC-released dust in space and check the flux necessary to maintain the cloud in a steady state.

  10. Sporadic Layer es and Siesmic Activity

    NASA Astrophysics Data System (ADS)

    Alimov, Obid; Blokhin, Alexandr; Kalashnikova, Tatyana

    2016-07-01

    To determine the influence of seismogenic disturbances on the calm state of the iono-sphere and assess the impact of turbulence development in sporadic-E during earthquake prepa-ration period we calculated the variation in the range of semitransparency ∆fES = f0ES - fbES. The study was based primarily on the ionograms obtained by vertical sounding of the ionosphere at Dushanbe at nighttime station from 15 to 29 August 1986. In this time period four successive earthquakes took place, which serves the purpose of this study of the impact of seis-mogenic processes on the intensity of the continuous generation of ionospheric turbulence. Analysis of the results obtained for seismic-ionospheric effects of 1986 earthquakes at station Dushanbe has shown that disturbance of ionospheric parameters during earthquake prepa-ration period displays a pronounced maximum with a duration of t = 1-6 hours. Ionospheric effects associated with the processes of earthquake preparation emerge quite predictably, which verifies seismogenic disturbances in the ionosphere. During the preparation of strong earthquakes, ionograms of vertical sounding produced at station Dushanbe - near the epicenter area - often shown the phenomenon of spreading traces of sporadic Es. It is assumed that the duration of manifestation of seismic ionospheric precursors in Du-shanbe τ = 1 - 6 hours may be associated with deformation processes in the Earth's crust and var-ious faults, as well as dissimilar properties of the environment of the epicentral area. It has been shown that for earthquakes with 4.5 ≤ M ≤ 5.5 1-2 days prior to the event iono-spheric perturbations in the parameters of the sporadic layer Es and an increase in the value of the range of semitransparency Es - ΔfEs were observed, which could lead to turbulence at altitudes of 100-130 km.

  11. Dynamical model for the toroidal sporadic meteors

    SciTech Connect

    Pokorný, Petr; Vokrouhlický, David; Nesvorný, David; Campbell-Brown, Margaret; Brown, Peter E-mail: vokrouhl@cesnet.cz E-mail: margaret.campbell@uwo.ca

    2014-07-01

    More than a decade of radar operations by the Canadian Meteor Orbit Radar have allowed both young and moderately old streams to be distinguished from the dispersed sporadic background component. The latter has been categorized according to broad radiant regions visible to Earth-based observers into three broad classes: the helion and anti-helion source, the north and south apex sources, and the north and south toroidal sources (and a related arc structure). The first two are populated mainly by dust released from Jupiter-family comets and new comets. Proper modeling of the toroidal sources has not to date been accomplished. Here, we develop a steady-state model for the toroidal source of the sporadic meteoroid complex, compare our model with the available radar measurements, and investigate a contribution of dust particles from our model to the whole population of sporadic meteoroids. We find that the long-term stable part of the toroidal particles is mainly fed by dust released by Halley type (long period) comets (HTCs). Our synthetic model reproduces most of the observed features of the toroidal particles, including the most troublesome low-eccentricity component, which is due to a combination of two effects: particles' ability to decouple from Jupiter and circularize by the Poynting-Robertson effect, and large collision probability for orbits similar to that of the Earth. Our calibrated model also allows us to estimate the total mass of the HTC-released dust in space and check the flux necessary to maintain the cloud in a steady state.

  12. Effect of Partnership Status on Preferences for Facial Self-Resemblance

    PubMed Central

    Lindová, Jitka; Little, Anthony C.; Havlíček, Jan; Roberts, S. Craig; Rubešová, Anna; Flegr, Jaroslav

    2016-01-01

    Self-resemblance has been found to have a context-dependent effect when expressing preferences for faces. Whereas dissimilarity preference during mate choice in animals is often explained as an evolutionary adaptation to increase heterozygosity of offspring, self-resemblance can be also favored in humans, reflecting, e.g., preference for kinship cues. We performed two studies, using transformations of facial photographs to manipulate levels of resemblance with the rater, to examine the influence of self-resemblance in single vs. coupled individuals. Raters assessed facial attractiveness of other-sex and same-sex photographs according to both short-term and long-term relationship contexts. We found a preference for dissimilarity of other-sex and same-sex faces in single individuals, but no effect of self-resemblance in coupled raters. No effect of sex of participant or short-term vs. long-term attractiveness rating was observed. The results support the evolutionary interpretation that dissimilarity of other-sex faces is preferred by uncoupled individuals as an adaptive mechanism to avoid inbreeding. In contrast, lower dissimilarity preference of other-sex faces in coupled individuals may reflect suppressed attention to attractiveness cues in potential alternative partners as a relationship maintenance mechanism, and its substitution by attention to cues of kinship and psychological similarity connected with greater likelihood of prosocial behavior acquisition from such persons. PMID:27378970

  13. Genomic aspects of sporadic Parkinson's disease.

    PubMed

    Riederer, P; Youdim, M B H; Mandel, S; Gerlach, M; Grünblatt, E

    2008-01-01

    Parkinson's disease (PD) is thought to be associated with oxidative stress mechanisms, as well as with glutamate receptor abnormalities, ubiquitin-proteasome dysfunction, inflammatory and cytokine activation, dysfunction in neurotrophic factors, damage to mitochondria, cytoskeletal abnormalities, synaptic dysfunction and activation of apoptotic pathways. To investigate these hypotheses, many researchers have applied molecular biology techniques to the study of neuronal cell death in these conditions. In this article, we discuss recent findings of gene expression in PD that may elucidate the usage of specific new biomarkers for sporadic PD and point to novel drug developments.

  14. Early Detection of Sporadic Pancreatic Cancer

    PubMed Central

    Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

    2015-01-01

    Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

  15. Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.

    PubMed

    Kobayashi, Atsushi; Parchi, Piero; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

    2016-06-01

    As an experimental model of acquired Creutzfeldt-Jakob disease (CJD), we performed transmission studies of sporadic CJD using knock-in mice expressing human prion protein (PrP). In this model, the inoculation of the sporadic CJD strain V2 into animals homozygous for methionine at polymorphic codon 129 (129 M/M) of the PRNP gene produced quite distinctive neuropathological and biochemical features, that is, widespread kuru plaques and intermediate type abnormal PrP (PrP(Sc) ). Interestingly, this distinctive combination of molecular and pathological features has been, to date, observed in acquired CJD but not in sporadic CJD. Assuming that these distinctive phenotypic traits are specific for acquired CJD, we revisited the literature and found two cases showing widespread kuru plaques despite the 129 M/M genotype, in a neurosurgeon and in a patient with a medical history of neurosurgery without dura mater grafting. By Western blot analysis of brain homogenates, we revealed the intermediate type of PrP(Sc) in both cases. Furthermore, transmission properties of brain extracts from these two cases were indistinguishable from those of a subgroup of dura mater graft-associated iatrogenic CJD caused by infection with the sporadic CJD strain V2. These data strongly suggest that the two atypical CJD cases, previously thought to represent sporadic CJD, very likely acquired the disease through exposure to prion-contaminated brain tissues. Thus, we propose that the distinctive combination of 129 M/M genotype, kuru plaques, and intermediate type PrP(Sc) , represents a reliable criterion for the identification of acquired CJD cases among presumed sporadic cases.

  16. An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis

    PubMed Central

    Rotunno, Melissa S.; Bosco, Daryl A.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that targets motor neurons, leading to paralysis and death within a few years of disease onset. While several genes have been linked to the inheritable, or familial, form of ALS, much less is known about the cause(s) of sporadic ALS, which accounts for ~90% of ALS cases. Due to the clinical similarities between familial and sporadic ALS, it is plausible that both forms of the disease converge on a common pathway and, therefore, involve common factors. Recent evidence suggests the Cu,Zn-superoxide dismutase (SOD1) protein to be one such factor that is common to both sporadic and familial ALS. In 1993, mutations were uncovered in SOD1 that represent the first known genetic cause of familial ALS. While the exact mechanism of mutant-SOD1 toxicity is still not known today, most evidence points to a gain of toxic function that stems, at least in part, from the propensity of this protein to misfold. In the wild-type SOD1 protein, non-genetic perturbations such as metal depletion, disruption of the quaternary structure, and oxidation, can also induce SOD1 to misfold. In fact, these aforementioned post-translational modifications cause wild-type SOD1 to adopt a “toxic conformation” that is similar to familial ALS-linked SOD1 variants. These observations, together with the detection of misfolded wild-type SOD1 within human post-mortem sporadic ALS samples, have been used to support the controversial hypothesis that misfolded forms of wild-type SOD1 contribute to sporadic ALS pathogenesis. In this review, we present data from the literature that both support and contradict this hypothesis. We also discuss SOD1 as a potential therapeutic target for both familial and sporadic ALS. PMID:24379756

  17. Two sisters resembling Gorlin-Chaudhry-Moss syndrome.

    PubMed

    Aravena, Teresa; Passalacqua, Cristóbal; Pizarro, Oscar; Aracena, Mariana

    2011-10-01

    The Gorlin-Chaudhry-Moss syndrome (GCMS), was describe initially by Gorlin et al. [Gorlin et al. (1960)] in two sisters with craniosynostosis, hypertrichosis, hypoplastic labia majora, dental defects, eye anomalies, patent ductus arteriosus, and normal intelligence. Two other sporadic instances have been documented. Here, we report on two sisters with a condition with some similarities to GCMS as well as some differences, which could represent either previously unreported variability in GCMS, or it may represent a novel disorder.

  18. Sporadic wind wave horse-shoe patterns

    NASA Astrophysics Data System (ADS)

    Annenkov, S. Yu.; Shrira, V. I.

    The work considers three-dimensional crescent-shaped patterns often seen on water surface in natural basins and observed in wave tank experiments. The most common of these 'horse-shoe-like' patterns appear to be sporadic, i.e., emerging and disappearing spontaneously even under steady wind conditions. The paper suggests a qualitative model of these structures aimed at explaining their sporadic nature, physical mechanisms of their selection and their specific asymmetric form. First, the phenomenon of sporadic horse-shoe patterns is studied numerically using the novel algorithm of water waves simulation recently developed by the authors (Annenkov and Shrira, 1999). The simulations show that a steep gravity wave embedded into widespectrum primordial noise and subjected to small nonconservative effects typically follows the simple evolution scenario: most of the time the system can be considered as consisting of a basic wave and a single pair of oblique satellites, although the choice of this pair tends to be different at different instants. Despite the effective low-dimensionality of the multimodal system dynamics at relatively sho ' rt time spans, the role of small satellites is important: in particular, they enlarge the maxima of the developed satellites. The presence of Benjamin-Feir satellites appears to be of no qualitative importance at the timescales under consideration. The selection mechanism has been linked to the quartic resonant interactions among the oblique satellites lying in the domain of five-wave (McLean's class II) instability of the basic wave: the satellites tend to push each other out of the resonance zone due to the frequency shifts caused by the quartic interactions. Since the instability domain is narrow (of order of cube of the basic wave steepness), eventually in a generic situation only a single pair survives and attains considerable amplitude. The specific front asymmetry is found to result from the interplay of quartic and quintet

  19. Gait analysis in a mouse model resembling Leigh disease.

    PubMed

    de Haas, Ria; Russel, Frans G; Smeitink, Jan A

    2016-01-01

    Leigh disease (LD) is one of the clinical phenotypes of mitochondrial OXPHOS disorders and also known as sub-acute necrotizing encephalomyelopathy. The disease has an incidence of 1 in 77,000 live births. Symptoms typically begin early in life and prognosis for LD patients is poor. Currently, no clinically effective treatments are available. Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. In this study we used the Ndufs4 knockout (Ndufs4(-/-)) mouse, a model of mitochondrial complex I deficiency. Ndusf4(-/-) mice exhibit progressive neurodegeneration, which closely resemble the human LD phenotype. When dissecting behavioral abnormalities in animal models it is of great importance to apply translational tools that are clinically relevant. To distinguish gait abnormalities in patients, simple walking tests can be assessed, but in animals this is not easy. This study is the first to demonstrate automated CatWalk gait analysis in the Ndufs4(-/-) mouse model. Marked differences were noted between Ndufs4(-/-) and control mice in dynamic, static, coordination and support parameters. Variation of walking speed was significantly increased in Ndufs4(-/-) mice, suggesting hampered and uncoordinated gait. Furthermore, decreased regularity index, increased base of support and changes in support were noted in the Ndufs4(-/-) mice. Here, we report the ability of the CatWalk system to sensitively assess gait abnormalities in Ndufs4(-/-) mice. This objective gait analysis can be of great value for intervention and drug efficacy studies in animal models for mitochondrial disease.

  20. Intentions vs. resemblance: understanding pictures in typical development and autism.

    PubMed

    Hartley, Calum; Allen, Melissa L

    2014-04-01

    Research has debated whether children reflect on artists' intentions when comprehending pictures, or instead derive meaning entirely from resemblance. We explore these hypotheses by comparing how typically developing toddlers and low-functioning children with autism (a population impaired in intentional reasoning) interpret abstract pictures. In Experiment 1, both groups mapped familiar object names onto abstract pictures, however, they related the same representations to different 3-D referents. Toddlers linked abstract pictures with intended referents they did not resemble, while children with autism mapped picture-referent relations based on resemblance. Experiment 2 showed that toddlers do not rely upon linguistic cues to determine intended referential relations. Experiment 3 confirmed that the responding of children with autism was not due to perseveration or associative word learning, and also provided independent evidence of their intention-reading difficulties. We argue that typically developing children derive meaning from the social-communicative intentions underlying pictures when resemblance is an inadequate cue to meaning. By contrast, children with autism do not reflect on artists' intentions and simply relate pictures to whatever they happen to resemble.

  1. Proteasomal dysfunction in sporadic Parkinson's disease.

    PubMed

    McNaught, Kevin St P; Jackson, Tehone; JnoBaptiste, Ruth; Kapustin, Alexander; Olanow, C Warren

    2006-05-23

    The cause and mechanism of neuronal death in sporadic Parkinson's disease (PD) continue to elude investigators. Recently, alterations in proteasomal function have been detected in the brain of patients with the illness. The biochemical basis of the defect and its relevance to the disease process are now being studied. The available results suggest that proteasomal dysfunction could underlie protein accumulation, Lewy body formation, and neuron death in PD. The cause of proteasomal dysfunction is unknown at present, but this could relate to gene mutations, oxidative damage, ATP depletion, or the actions of environmental toxins. It remains to be established if proteasomal dysfunction plays a primary or a secondary role in the initiation or progression of the neurodegenerative process in PD.

  2. Introduction to sporadic groups for physicists

    NASA Astrophysics Data System (ADS)

    Boya, Luis J.

    2013-04-01

    We describe the collection of finite simple groups, with a view to physical applications. We recall first the prime cyclic groups Zp and the alternating groups Altn > 4. After a quick revision of finite fields {F}_q, q = pf, with p prime, we consider the 16 families of finite simple groups of Lie type. There are also 26 extra ‘sporadic’ groups, which gather in three interconnected ‘generations’ (with 5+7+8 groups) plus the pariah groups (6). We point out a couple of physical applications, including constructing the biggest sporadic group, the ‘Monster’ group, with close to 1054 elements from arguments of physics, and also the relation of some Mathieu groups with compactification in string and M-theory. This article is dedicated to the memory of Juan Sancho Guimerá.

  3. A hypothesis to explain accuracy of wasp resemblances.

    PubMed

    Boppré, Michael; Vane-Wright, Richard I; Wickler, Wolfgang

    2017-01-01

    Mimicry is one of the oldest concepts in biology, but it still presents many puzzles and continues to be widely debated. Simulation of wasps with a yellow-black abdominal pattern by other insects (commonly called "wasp mimicry") is traditionally considered a case of resemblance of unprofitable by profitable prey causing educated predators to avoid models and mimics to the advantage of both (Figure 1a). However, as wasps themselves are predators of insects, wasp mimicry can also be seen as a case of resemblance to one's own potential antagonist. We here propose an additional hypothesis to Batesian and Müllerian mimicry (both typically involving selection by learning vertebrate predators; cf. Table 1) that reflects another possible scenario for the evolution of multifold and in particular very accurate resemblances to wasps: an innate, visual inhibition of aggression among look-alike wasps, based on their social organization and high abundance. We argue that wasp species resembling each other need not only be Müllerian mutualists and that other insects resembling wasps need not only be Batesian mimics, but an innate ability of wasps to recognize each other during hunting is the driver in the evolution of a distinct kind of masquerade, in which model, mimic, and selecting agent belong to one or several species (Figure  1b). Wasp mimics resemble wasps not (only) to be mistaken by educated predators but rather, or in addition, to escape attack from their wasp models. Within a given ecosystem, there will be selection pressures leading to masquerade driven by wasps and/or to mimicry driven by other predators that have to learn to avoid them. Different pressures by guilds of these two types of selective agents could explain the widely differing fidelity with respect to the models in assemblages of yellow jackets and yellow jacket look-alikes.

  4. Investigations on the Plasma Irregularities Associated with Midlatitude Sporadic-E Layers

    NASA Astrophysics Data System (ADS)

    Riggin, Dennis Marshall

    The Cornell University Portable Radar Interferometer (CUPRI), a 50 MHz Doppler radar system, was operated during May and August/September, 1983, on the island of St. Croix (17.7(DEGREES)N, 64.8(DEGREES)W) to study the plasma instabilities associated with nighttime sporadic-E layers. The CURPI beam was directed over Arecibo, Puerto Rico, during these experiments and on several nights concurrent F region plasma drifts and electron density profiles were measured by the Arecibo Observatory's 430 MHz radar. CUPRI was stationed at Ft. Macon, North Carolina, in August 1984 for another collaborative experiment involving the launch of a sounding rocket from Wallops Island, Virginia. The usual E region linear plasma fluid theory is adequate to explain many features of the 3-m waves probed by the radar. Measurements at St. Croix determined that the 3-m sporadic-E irregularities are highly field-aligned (to within 0.3(DEGREES)) as the theory predicts. Some of the radar spectra obtained from St. Croix are narrow, similar to equatorial type 1. We find from linear theory that the type 1 3-m waves could be generated at midlatitudes with drift velocities well below the sound speed because of the very sharp gradients associated with metallic ion sporadic-E layers. Two events during the St. Croix campaign show evidence of large scale plasma waves, with horizontal wavelengths of 6-10 km and periods of 2-5 minutes. These waves were large in amplitude with mean Doppler velocities at times exceeding 250 m/s, and the power spectra closely resemble those obtained at the magnetic equator during type 1 conditions. The rocket measurements also revealed large scale plasma irregularities in a low density region above a sporadic-E layer. The large scale structure had an apparent wavelength of about 2 km and modulated the ambient density (10('4) cm('-3)) by almost 100%. We attribute the large scale waves seen during these experiments to the same gradient drift instability mechanism responsible

  5. Reflection of radio waves by sporadic-E layers

    NASA Technical Reports Server (NTRS)

    Miller, K. L.; Smith, L. G.

    1977-01-01

    A full-wave analysis of the reflection coefficient is developed and applied to electron-density profiles of midlatitude sporadic-E layers observed by rocket-borne probes. It is shown that partial reflection from the large electron-density gradients at the upper and lower boundaries of sporadic-E layers does not account for the partial transparency observed by ionosondes.

  6. Studies of sporadic E (Es) associated with the main ionospheric trough

    SciTech Connect

    Rodger, A.S.; Morrell, C.; Dudeney, J.R.

    1983-11-01

    Sporadic E, or E(s) events under the main F region trough have been confirmed on the basis of ionograms from a vertical incidence ionosonde at Halley Bay, Antarctica. Analyses indicate that E(s) is frequently observable under both the equatorward and the poleward edges of the trough, as well as poleward of it. Before magnetic midnight, E(s) layers whose semithickness resembles those of the normal E layer are common, in contrast to layers seen after magnetic midnight which show the characteristics of thin E(s) layers. A possible explanation of the observed change in the E(s) layer characteristics at magnetic midnight is related to differences in the type and spectra of the precipitating particles. It is shown that the redistribution of ionization by the convection electric field may be important. 40 references.

  7. ASL Nominal Constructions Involving Signs That Resemble Pronouns

    ERIC Educational Resources Information Center

    Sloan, Vivion Smith

    2013-01-01

    This dissertation examines six different types of noun phrases that commonly occur in American Sign Language. These noun phrases all include at least a head noun and one of four signs resembling a pronoun. Videos of natural ASL discourses are gathered, multiple instances of the six types of noun phrases are identified, and their meanings are…

  8. Differential grandparental investment - the impact of phenotypic resemblance.

    PubMed

    Schlee, Juliane; Kirchengast, Sylvia

    2015-01-01

    Differential grandparental investment is mainly explained as a result of paternity uncertainty. Phenotypic resemblance may be interpreted as an indicator of genetically relatedness. Consequently the present study focused on the impact of phenotypic resemblance on grandparental investment, i.e. solicitude, contact frequency and quality of relationship. 213 adults persons between the age 19 and 32 years (x = 25.5; SD = 3.4) were enrolled in the study. Data concerning grandparental investment during childhood were collected retrospectively using a 30 item questionnaire. Grandparental investment patterns differed significantly according grandparent category. In detail maternal grandmothers showed the highest contact frequency and the highest solicitude while - as to be expected - the paternal grandfather exhibited the lowest degree of investment. Grandparental investment was independent of grandparent category mainly influenced by residential distance. Phenotypic resemblance had an impact on grandparental investment independent of residential distance. This was first of all true of paternal grandfathers. An impact of phenotypic resemblance on grandparental investment patters can be assumed.

  9. Allergic Contact Dermatitis to Benzoyl Peroxide Resembling Impetigo.

    PubMed

    Kim, Changhyun; Craiglow, Brittany G; Watsky, Kalman L; Antaya, Richard J

    2015-01-01

    A 17-year-old boy presented with recurring severe dermatitis of the face of 5-months duration that resembled impetigo. He had been treated with several courses of antibiotics without improvement. Biopsy showed changes consistent with allergic contact dermatitis and patch testing later revealed sensitization to benzoyl peroxide, which the patient had been using for the treatment of acne vulgaris.

  10. Sporadic aurorae observed in East Asia

    NASA Astrophysics Data System (ADS)

    Willis, D. M.; Stephenson, F. R.; Fang, Huiping

    2007-03-01

    All the accessible auroral observations recorded in Chinese and Japanese histories during the interval AD 1840-1911 are investigated in detail. Most of these auroral records have never been translated into a Western language before. The East Asian auroral reports provide information on the date and approximate location of each auroral observation, together with limited scientific information on the characteristics of the auroral luminosity such as colour, duration, extent, position in the sky and approximate time of occurrence. The full translations of the original Chinese and Japanese auroral records are presented in an appendix, which contains bibliographic details of the various historical sources. (There are no known reliable Korean observations during this interval.) A second appendix discusses a few implausible "auroral" records, which have been rejected. The salient scientific properties of all exactly dated and reliable East Asian auroral observations in the interval AD 1840-1911 are summarised succinctly. By comparing the relevant scientific information on exactly dated auroral observations with the lists of great geomagnetic storms compiled by the Royal Greenwich Observatory, and also the tabulated values of the Ak (Helsinki) and aa (Greenwich and Melbourne) magnetic indices, it is found that 5 of the great geomagnetic storms (aa>150 or Ak>50) during either the second half of the nineteenth century or the first decade of the twentieth century are clearly identified by extensive auroral displays observed in China or Japan. Indeed, two of these great storms produced auroral displays observed in both countries on the same night. Conversely, at least 29 (69%) of the 42 Chinese and Japanese auroral observations occurred at times of weak-to-moderate geomagnetic activity (aa or Ak≤50). It is shown that these latter auroral displays are very similar to the more numerous (about 50) examples of sporadic aurorae observed in the United States during the interval AD

  11. Sporadic nocturnal frontal lobe epilepsy: A consecutive series of 8 cases

    PubMed Central

    Yeh, Shih-Bin; Schenck, Carlos H.

    2014-01-01

    Objective To present findings on a series of cases of sporadic nocturnal frontal lobe epilepsy (NFLE), a form of NFLE that is infrequently reported, in contrast to familial (autosomal dominant) NFLE. Both forms of NFLE need to be distinguished from parasomnias, nocturnal temporal lobe epilepsy, and other nocturnal disorders. Methods Eight consecutive cases of sporadic NFLE were evaluated at a sleep clinic in Taiwan. All patients had clinical evaluations, daytime waking and sleeping EEGs, brain MRIs, and overnight video-polysomnography (vPSG) with seizure montage. Results Gender was equal (four males, four females); mean age was 18.4 yrs (range, 7–41 yrs). Age of NFLE onset was by puberty. Premorbid history was negative for any neurologic, medical or psychiatric disorder. NFLE subtypes: nocturnal paroxysmal dystonia, n=6; paroxysmal arousals, n=2. MRI brain scan abnormalities with clinical correlates were found in one patient. Daytime awake EEGs were negative for ictal/interictal activity in all patients, but two patients had daytime sleep EEGs with interictal epileptiform EEG activity. During vPSG studies, three of eight patients with NFLE seizure events had concurrent epileptiform EEG activity, and two patients had interictal epileptiform EEG activity during their vPSG studies. No case had a spontaneous remission. Anticonvulsant therapy was highly effective in all eight cases (>75% reduction in seizure frequency). Discussion These cases confirm that sporadic NFLE closely resembles familial NFLE, and comprises a set of distinct clinical manifestations, with variable intensity, and variable scalp EEG epileptiform abnormalities across sleep and wakefulness, which have previously been identified in Caucasian patients from Europe and North America. PMID:26483923

  12. Congenital symmetrical weakness of the upper limbs resembling brachial plexus palsy: a possible sequel of drug toxicity in first trimester of pregnancy?

    PubMed

    Philpot, J; Muntoni, F; Skellett, S; Dubowitz, V

    1995-01-01

    We report a 14-month-old girl with a symmetrical paralysis from birth, limited to the upper limbs and resembling a severe, complete bilateral brachial plexus palsy. The presence of dimples over the wrists, shoulders and scapulae and abnormal palmar dermatoglyphics suggested an early prenatal onset. Previous reports and the course of the disease in our case suggest this sporadic condition is not progressive. Although no definitive causative factor has been identified in previously reported cases, the affection in our case is possibly related to Debendox (Bendectin) and nitrofurantoin taken in early pregnancy for nausea and renal tract infection, respectively.

  13. Radar studies of long-wavelength waves associated with mid-latitude sporadic E layers

    NASA Astrophysics Data System (ADS)

    Riggin, D.; Swartz, W. E.; Providakes, J.; Farley, D. T.

    1986-07-01

    The Cornell University Portable Radar Interferometer (CUPRI), a 50-MHz Doppler radar system, was operated during May and August/September 1983 on the island of St. Croix (17.7 deg N, 64.8 deg W) to study the plasma instabilities associated with nighttime sporadic E layers. Two events, on May 7 and August 22, show evidence of large-amplitude waves, with apparent horizontal wavelengths of 10-12 km and periods of 2-6 min. These apparent wavelengths are upper limits for the true wavelengths. The CUPRI beam was directed over Arecibo, PR, and on May 7, concurrent electron density profiles within the CUPRI scattering volume were measured by the Arecibo Observatory's 430-MHz radar. During the stronger event of August 22, radar echoes were received from several altitudes up to 130 km. Large mean Doppler velocities (at times exceeding 250 m/s) were observed during this event, and the power spectra closely resemble those obtained at the magnetic equator during type 1 conditions. It is believed (1) that the midlatitude large-scale waves are generated by the same gradient drift instability mechanism responsible for equatorial large-scale waves, and (2) that the type 1 3-m waves can be generated at midlatitudes with drift velocities well below the sound speed because of the very sharp plasma density gradients associated with metallic ion sporadic E layers.

  14. Angiogenesis and lymphangiogenesis in sporadic hepatic angiomyolipoma.

    PubMed

    Xian, Zhi-Hong; Cong, Wen-Ming; Lu, Xin-Yuan; Yu, Hua; Wu, Meng-Chao

    2011-07-15

    Angiogenesis and lymphangiogenesis are critical processes for tumor growth, invasion, and metastasis. The present study aimed to investigate the distribution and clinical significance of angiogenesis and lymphangiogenesis in hepatic angiomyolipoma (AML). We performed immunohistochemical staining for endothelial cell markers (CD34 and podoplanin) on 80 cases of sporadic hepatic AMLs. Microvessel density (MVD) and lymphatic vessel density (LVD) were determined in intratumoral and peritumoral regions and adjacent non-tumorous liver tissues. All hepatic AMLs showed positive staining for CD34 and podoplanin. Intratumoral and peritumoral MVDs and LVDs were significantly higher than those in adjacent liver tissues (P<0.001). No statistical difference in both MVD and LVD was found between intratumoral and peritumoral areas. Large tumors (>5cm) had a significantly increased MVD and LVD as compared with smaller tumors. A significant positive correlation was found between average LVDs and MVDs (r=0.567, P<0.001), and LVDs were a relatively lower event as compared with MVDs. Double immunostaining revealed that no neoplastic cells positive for HMB-45, an antibody reacting with melanosome-associated antigen, were concurrently immunoreactive for endothelial cell markers. In conclusion, intratumoral and peritumoral angiogenesis and lymphangiogenesis commonly occur in hepatic AMLs, thus representing potential therapeutic targets for this disease.

  15. Anterior cervical hypertrichosis: a sporadic case

    PubMed Central

    Bostan, Sezen; Yaşar, Şirin; Serdar, Zehra Aşiran; Gizlenti, Sevda

    2016-01-01

    Anterior cervical hypertrichosis is a very rare form of primary localized hypertrichosis. It consists of a tuft of terminal hair on the anterior neck just above the laryngeal prominence. The etiology is still unknown. In this article, we reported a 15-year-old female patient who presented to our clinic with a complaint of hypertrichosis on the anterior aspect of the neck for the last five years. Her past medical history revealed no pathology except for vesicoureteral reflux. On the basis of clinical presentation, our patient was diagnosed with anterior cervical hypertrichosis and she was considered to be a sporadic case due to lack of other similar cases in familial history. To date, 33 patients with anterior cervical hypertrichosis have been reported. Anterior cervical hypertrichosis can be associated with other abnormalities, but it frequently presents as an isolated defect (70%). The association of vesicoureteral reflux and anterior cervical hypertrichosis which was observed in our patient might be coincidental. So far, no case of anterior cervical hypertrichosis associated with vesicoureteral reflux has been reported in the literature. PMID:27103865

  16. Synchrony in Metapopulations with Sporadic Dispersal

    NASA Astrophysics Data System (ADS)

    Jeter, Russell; Belykh, Igor

    2015-06-01

    We study synchronization in ecological networks under the realistic assumption that the coupling among the patches is sporadic/stochastic and due to rare and short-term meteorological conditions. Each patch is described by a tritrophic food chain model, representing the producer, consumer, and predator. If all three species can migrate, we rigorously prove that the network can synchronize as long as the migration occurs frequently, i.e. fast compared to the period of the ecological cycle, even though the network is disconnected most of the time. In the case where only the top trophic level (i.e. the predator) can migrate, we reveal an unexpected range of intermediate switching frequencies where synchronization becomes stable in a network which switches between two nonsynchronous dynamics. As spatial synchrony increases the danger of extinction, this counterintuitive effect of synchrony emerging from slower switching dispersal can be destructive for overall metapopulation persistence, presumably expected from switching between two dynamics which are unfavorable to extinction.

  17. Microsatellite instability in early sporadic breast cancer.

    PubMed Central

    Shaw, J. A.; Walsh, T.; Chappell, S. A.; Carey, N.; Johnson, K.; Walker, R. A.

    1996-01-01

    We have studied the incidence of microsatellite instability at three trinucleotide repeats and seven dinucleotide repeats from five chromosomal regions, in a group of 30 mammographically detected 'early' invasive breast cancers and correlated its occurrence with clinicopathological parameters. The myotonic dystrophy (DM-1) trinucleotide repeat was analysed in 48 additional cases. In 4 out of 78 (5%) paired tumour-normal DNA samples we found evidence of somatic microsatellite instability at DM-1: a novel allele of a different size was seen in the tumour DNA which was not present in the normal DNA sample. All four tumours that showed evidence of instability were from the core group of 30 cases (13%) and were well or moderately differentiated, oestrogen receptor-positive, infiltrating ductal carcinomas. Two of these tumours were unstable at nine of ten loci studied, both trinucleotide and dinucleotide repeats. DNA prepared from different normal tissues showed no evidence of instability, for all four instability cases. These data indicate that microsatellite instability is specific to the tumour DNA and is an early event in the genesis of some sporadic breast cancers. Images Figure 1 PMID:8645585

  18. Anterior cervical hypertrichosis: a sporadic case.

    PubMed

    Bostan, Sezen; Yaşar, Şirin; Serdar, Zehra Aşiran; Gizlenti, Sevda

    2016-03-01

    Anterior cervical hypertrichosis is a very rare form of primary localized hypertrichosis. It consists of a tuft of terminal hair on the anterior neck just above the laryngeal prominence. The etiology is still unknown. In this article, we reported a 15-year-old female patient who presented to our clinic with a complaint of hypertrichosis on the anterior aspect of the neck for the last five years. Her past medical history revealed no pathology except for vesicoureteral reflux. On the basis of clinical presentation, our patient was diagnosed with anterior cervical hypertrichosis and she was considered to be a sporadic case due to lack of other similar cases in familial history. To date, 33 patients with anterior cervical hypertrichosis have been reported. Anterior cervical hypertrichosis can be associated with other abnormalities, but it frequently presents as an isolated defect (70%). The association of vesicoureteral reflux and anterior cervical hypertrichosis which was observed in our patient might be coincidental. So far, no case of anterior cervical hypertrichosis associated with vesicoureteral reflux has been reported in the literature.

  19. Aneurysm in a Large Sporadic Renal Angiomyolipoma

    PubMed Central

    Al Omran, Bedoor; Ansari, Naseem

    2016-01-01

    Angiomyolipomas (AMLs) are the most common mesenchymal renal neoplasms and are classified as neoplasms of perivascular epithelioid cells (PEComa). AML is usually a benign neoplasm arising most often in the kidney although it has been described in a wide variety of sites. Most patients are adults, and one-third suffer from tuberous sclerosis. We describe a case of renal AML in a 54-year-old Bahraini woman who presented to the Bahrain Defence Force Hospital with right flank pain and hematuria, and who was known to have rheumatoid arthritis but had no cutaneous or other stigmata of tuberous sclerosis. It is the largest AML reported in Bahrain and is also striking for the fact that it contained an intratumoral aneurysm that ruptured causing symptoms leading to the radiological diagnosis of renal mass. Furthermore, the occurrence of an aneurysm in sporadic AML, as in our case, is rare since the large majority tend to be seen in association with tuberous sclerosis. PMID:27162594

  20. Sporadic and hereditary amyotrophic lateral sclerosis (ALS).

    PubMed

    Ajroud-Driss, Senda; Siddique, Teepu

    2015-04-01

    Genetic discoveries in ALS have a significant impact on deciphering molecular mechanisms of motor neuron degeneration. The identification of SOD1 as the first genetic cause of ALS led to the engineering of the SOD1 mouse, the backbone of ALS research, and set the stage for future genetic breakthroughs. In addition, careful analysis of ALS pathology added valuable pieces to the ALS puzzle. From this joint effort, major pathogenic pathways emerged. Whereas the study of TDP43, FUS and C9ORF72 pointed to the possible involvement of RNA biology in motor neuron survival, recent work on P62 and UBQLN2 refocused research on protein degradation pathways. Despite all these efforts, the etiology of most cases of sporadic ALS remains elusive. Newly acquired genomic tools now allow the identification of genetic and epigenetic factors that can either increase ALS risk or modulate disease phenotype. These developments will certainly allow for better disease modeling to identify novel therapeutic targets for ALS. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  1. [The Nomenclature and Classification of Sporadic Spinocerebellar Degeneration].

    PubMed

    Koga, Shunsuke

    2016-12-01

    Spinocerebellar degeneration (SCD) is a neurodegenerative disease characterized by progressive cerebellar ataxia. SCD has a wide range of clinical, pathological, and genetic features, including whether the disease is sporadic or hereditary, and whether it manifests as purely cerebellar or affects multiple systems. Therefore, the classification of SCD has been complicated and has changed over time. Recent advances in genetic testing have shed light on the classification of hereditary SCD. In contrast, the classification of sporadic SCD remains chaotic and there exist nomenclature discrepancies in sporadic SCD between Japanese and English literature. Sporadic SCD is usually divided into multiple system atrophy and cortical cerebellar atrophy in Japanese literature, but the latter nomenclature seems to be uncommon in English literature. The aim of this review is to reconsider the nomenclature and classification of sporadic SCD. At this time, sporadic adult-onset ataxia of unknown etiology is an acceptable term to describe a case of sporadic SCD that does not fit the multiple system atrophy classification.

  2. Arteriovenous shunts resembling patent ductus arteriosus in dogs: 3 cases.

    PubMed

    Fujii, Yoko; Aoki, Takuma; Takano, Hiroshi; Ishikawa, Ryokichi; Wakao, Yoshito

    2009-12-01

    Three dogs presented for the evaluation of cardiac murmurs were diagnosed with aberrant arteriovenous shunts. All cases demonstrated the following findings: 1) relatively soft continuous murmur loudest at the left heart base resembling patent ductus arteriosus (PDA); 2) shunt flow signals in the pulmonary artery on echocardiography; and 3) no PDA on selective angiography, but evidence of anomalous shunting vessels from thoracic aorta to pulmonary vasculature. An aberrant arteriovenous shunt should be considered when a continuous murmur of relatively small intensity is heard.

  3. Sporadic phaeochromocytoma in childhood: clinical and molecular variability.

    PubMed

    Pozo, Jesús; Muñoz, Maria Teresa; Martos, Gabriel; Argente, Jesús

    2005-06-01

    Sporadic phaeochromocytoma is an infrequent tumour during paediatric age and may or may not be associated with specific autosomal dominant inherited cancer syndromes such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau syndrome (VHL) type 2 or neurofibromatosis (NF) type 1. We report two cases of benign, adrenal, and unilateral phaeochromocytoma that clearly demonstrate the clinical and molecular heterogeneity of this disease during the paediatric period. The first patient presented a characteristic symptomatic form of sporadic phaeochromocytoma. The second patient, an incidental finding, was practically asymptomatic and had a de novo germline point mutation in the VHL gene (Arg167Trp). The frequency of de novo mutations in susceptible genes (especially the VHL gene) in paediatric patients with sporadic phaeochromocytoma and the elevated mortality of these cancer syndromes suggest that screening for mutations should be performed even in cases of non-familial sporadic phaeochromocytoma.

  4. Near Earth space sporadic radio emission busts occurring during sunrise

    NASA Technical Reports Server (NTRS)

    Dudnik, A. V.; Zaljubovsky, I. I.; Kartashev, V. M.; Lasarev, A. V.; Shmatko, E. S.

    1985-01-01

    During the period of low solar activity at sunrise the effect of sporadic high frequency near Earth space radio emission was experimentally discovered at middle latitudes. The possible mechanism of its origin is discussed.

  5. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

    PubMed Central

    Kallenberg, K.; Summers, D. M.; Romero, C.; Taratuto, A.; Heinemann, U.; Breithaupt, M.; Varges, D.; Meissner, B.; Ladogana, A.; Schuur, M.; Haik, S.; Collins, S. J.; Jansen, Gerard H.; Stokin, G. B.; Pimentel, J.; Hewer, E.; Collie, D.; Smith, P.; Roberts, H.; Brandel, J. P.; van Duijn, C.; Pocchiari, M.; Begue, C.; Cras, P.; Will, R. G.; Sanchez-Juan, P.

    2009-01-01

    Several molecular subtypes of sporadic Creutzfeldt–Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt–Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt–Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt–Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Patients with sporadic Creutzfeldt–Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as ‘suspected sporadic Creutzfeldt–Jakob disease’ but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt–Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt–Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic

  6. Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients.

    PubMed

    Takatsuki, Hanae; Fuse, Takayuki; Nakagaki, Takehiro; Mori, Tsuyoshi; Mihara, Ban; Takao, Masaki; Iwasaki, Yasushi; Yoshida, Mari; Murayama, Shigeo; Atarashi, Ryuichiro; Nishida, Noriyuki; Satoh, Katsuya

    2016-10-01

    Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 10(6)/g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 10(6)/g SD50 did not exist the infectivity.

  7. Tumor LOH analysis provides reliable linkage information for prenatal genetic testing of sporadic NF1 patients.

    PubMed

    Serra, Eduard; Pros, Eva; García, Carles; López, Eva; Gili, M Lluïsa; Gómez, Carolina; Ravella, Anna; Capellá, Gabriel; Blanco, Ignacio; Lázaro, Conxi

    2007-09-01

    The neurofibromatosis type 1 gene has one of the highest mutation rates in humans: about 50% of NF1 patients are de novo cases. Although direct mutation characterization has greatly improved over the past decade, in the context of clinical genetics services worldwide, there is still a significant number of patients for which, while fulfilling NF1 clinical criteria, no constitutive mutation is found at a desired time. This is particularly critical for prenatal genetic testing of sporadic cases. Here we describe the use of loss of heterozygosity information in neurofibromas to obtain linkage information on the affected NF1 haplotype, which may be applied for prenatal testing in sporadic patients. However, proper genetic counseling should be provided regarding the possibility of somatic mosaicism.

  8. Personalised pathway analysis reveals association between DNA repair pathway dysregulation and chromosomal instability in sporadic breast cancer.

    PubMed

    Liu, Chao; Srihari, Sriganesh; Lal, Samir; Gautier, Benoît; Simpson, Peter T; Khanna, Kum Kum; Ragan, Mark A; Lê Cao, Kim-Anh

    2016-01-01

    The Homologous Recombination (HR) pathway is crucial for the repair of DNA double-strand breaks (DSBs) generated during DNA replication. Defects in HR repair have been linked to the initiation and development of a wide variety of human malignancies, and exploited in chemical, radiological and targeted therapies. In this study, we performed a personalised pathway analysis independently for four large sporadic breast cancer cohorts to investigate the status of HR pathway dysregulation in individual sporadic breast tumours, its association with HR repair deficiency and its impact on tumour characteristics. Specifically, we first manually curated a list of HR genes according to our recent review on this pathway (Liu et al., 2014), and then applied a personalised pathway analysis method named Pathifier (Drier et al., 2013) on the expression levels of the curated genes to obtain an HR score quantifying HR pathway dysregulation in individual tumours. Based on the score, we observed a great diversity in HR dysregulation between and within gene expression-based breast cancer subtypes, and by using two published HR-defect signatures, we found HR pathway dysregulation reflects HR repair deficiency. Furthermore, we identified a novel association between HR pathway dysregulation and chromosomal instability (CIN) in sporadic breast cancer. Although CIN has long been considered as a hallmark of most solid tumours, with recent extensive studies highlighting its importance in tumour evolution and drug resistance, the molecular basis of CIN in sporadic cancers remains poorly understood. Our results imply that HR pathway dysregulation might contribute to CIN in sporadic breast cancer.

  9. Emission spectrum of a sporadic fireball afterglow

    NASA Astrophysics Data System (ADS)

    Madiedo, J.; Trigo-Rodríguez, J.

    2014-07-01

    A mag. -11 fireball was imaged over southern Spain on April 14, 2013 at 22:35:49.8 ± 0.1s UTC. Its emission spectrum was also obtained. This event was assigned the SPMN code 140413 after the recording date. By the end of its atmospheric path, it exhibited a very bright flare which resulted in a persistent train whose spectrum was recorded. Here we present a preliminary analysis of this event and focus special attention on the evolution of the main emission lines in the spectrum of the afterglow. An array of low-lux CCD video devices (models 902H and 902H Ultimate from Watec Co.) operating from our stations at Sevilla and El Arenosillo was employed to record the SPMN140413 fireball. The operation of these systems is explained in [1,2]. Some of these are configured as spectrographs by attaching holographic diffraction gratings (1000 lines/mm) to the objective lens [3]. To calculate the atmospheric trajectory, radiant, and orbit we have employed our AMALTHEA software, which follows the planes intersection method [4]. The spectrum was analyzed with our CHIMET application [5]. The parent meteoroid impacted the atmosphere with an initial velocity of 28.9 ± 0.3 km/s and the fireball began at a height of 104.4 ± 0.5 km. The event ended at 80.7 ± 0.5 km above the ground level, with the main flare taking place at 83 ± 0.5 km. The calculated radiant and orbital parameters confirm the sporadic nature of the bolide. The calibrated emission spectrum shows that the most important contributions correspond to the Na I-1 (588.9 nm) and Mg I-2 (517.2 nm) multiplets. In the ultraviolet, the contribution from the H and K lines from Ca was also identified. As usual in meteor spectra, most of the lines correspond to Fe I. The train spectrum was recorded during about 0.12 seconds. This provided the evolution with time of the intensity of the emission lines in this signal. The contributions from Mg I, Na I, Ca I, Fe I, Ca II, and O I were identified in the afterglow, with the Na I-1

  10. Extending disorder: essentialism, family resemblance and secondary sense.

    PubMed

    Pickering, Neil

    2013-05-01

    It is commonly thought that mental disorder is a valid concept only in so far as it is an extension of or continuous with the concept of physical disorder. A valid extension has to meet two criteria: determination and coherence. Essentialists meet these criteria through necessary and sufficient conditions for being a disorder. Two Wittgensteinian alternatives to essentialism are considered and assessed against the two criteria. These are the family resemblance approach and the secondary sense approach. Where the focus is solely on the characteristics or attributes of things, both these approaches seem to fail to meet the criteria for valid extension. However, this focus on attributes is mistaken. The criteria for valid extension are met in the case of family resemblance by the pattern of characteristics associated with a concept, and by the limits of intelligibility of applying a concept. Secondary sense, though it may have some claims to be a good account of the relation between physical and mental disorder, cannot claim to meet the two criteria of valid extension.

  11. Ritodrine-induced pustular eruptions distinctly resembling impetigo herpetiformis.

    PubMed

    Kuwabara, Yoshimitsu; Sato, Atsuki; Abe, Hiroko; Abe, Sumino; Kawai, Naoki; Takeshita, Toshiyuki

    2011-01-01

    A 27-year-old nulligravida woman without a history of dermatosis was hospitalized for threatened preterm labor at 29 weeks' gestation; therefore, continuous infusion of ritodrine hydrochloride was started. At 31 weeks' gestation, erythematous plaques appeared and spread over the body surface; therefore, a topical steroid preparation was applied. At 32 weeks' gestation, the eruptions developed into irregular annular areas of erythema with multiple pustules accompanied by severe itching, and oral prednisolone treatment was started. Bacterial cultures of the pustules were negative, and a crural cutaneous biopsy revealed Kogoj's spongiform pustules. Based on the clinicopathological findings, the most likely diagnosis was impetigo herpetiformis, which causes cutaneous symptoms closely resembling pustular psoriasis in pregnant females without a history of psoriasis. To rule out ritodrine-induced pustular eruptions, the ritodrine infusion was stopped and treatment with an MgSO(4) preparation was started at 33 weeks' 3 days' gestation; however, the uterine contractions could not be suppressed. Because of the patient's highly edematous, severely painful feet, a cesarean section was performed the same day. Within several days of delivery, the eruptions began to resolve, and no recurrence was observed after treatment with oral prednisolone was stopped 31 days after delivery. On the basis of a positive patch test for ritodrine, we diagnosed pustular drug eruptions caused by ritodrine hydrochloride. Although ritodrine-induced pathognomonic cutaneous eruptions are rare, we would like to emphasize that ritodrine can cause drug-induced pustular eruptions distinctly resembling life-threatening impetigo herpetiformis.

  12. PARK2 enhancement is able to compensate mitophagy alterations found in sporadic Alzheimer's disease

    PubMed Central

    Martín-Maestro, Patricia; Gargini, Ricardo; Perry, George; Avila, Jesús; García-Escudero, Vega

    2016-01-01

    Mitochondrial anomalies have been previously reported in patients′ brain and peripheral tissue, suggesting their relevance in sporadic Alzheimer's disease (AD). The present work evaluates mitochondrial function and recycling in human fibroblasts and brain biopsies. Functional studies using patients′ skin fibroblasts showed slower mitochondrial membrane potential recovery after a mitochondrial insult together with alterations in lysosomes and autophagy, accompanied by an increase of oxidized and ubiquitinated proteins. Impairment in mitophagy has been proven in these cells due to diminished PARK2 and insufficient vesicle induction, accumulating depolarized mitochondria and PINK1. Augmented Δ1 PINK1 fragment levels suggest an inhibitory effect over PARK2 translocation to the mitochondria, causing the accumulation of activated PINK1. Moreover, the overexpression of PARK2 diminished ubiquitinated proteins accumulation, improves its targeting to mitochondria and potentiates autophagic vesicle synthesis. This allows the reversion of mitophagy failure reflected in the recovery of membrane potential and the decrease of PINK1 and mitochondria accumulation. Sporadic AD fibroblasts exhibited alterations similar to what it could be found in patients’ hippocampal samples at early stages of the disease, where there was an accumulation of PINK1 and Δ1 PINK1 together with abnormally increased mitochondrial content. Our findings indicate that mitophagy alterations can be considered a new hallmark of sporadic AD and validate the use of fibroblasts for modelling this pathology. PMID:26721933

  13. ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.

    PubMed

    Halim, Danny; Hofstra, Robert M W; Signorile, Luca; Verdijk, Rob M; van der Werf, Christine S; Sribudiani, Yunia; Brouwer, Rutger W W; van IJcken, Wilfred F J; Dahl, Niklas; Verheij, Joke B G M; Baumann, Clarisse; Kerner, John; van Bever, Yolande; Galjart, Niels; Wijnen, Rene M H; Tibboel, Dick; Burns, Alan J; Muller, Françoise; Brooks, Alice S; Alves, Maria M

    2016-02-01

    Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS) is a rare congenital disorder, in which heterozygous missense variants in the Enteric Smooth Muscle actin γ-2 (ACTG2) gene have been recently identified. To investigate the mechanism by which ACTG2 variants lead to MMIHS, we screened a cohort of eleven MMIHS patients, eight sporadic and three familial cases, and performed immunohistochemistry, molecular modeling and molecular dynamics (MD) simulations, and in vitro assays. In all sporadic cases, a heterozygous missense variant in ACTG2 was identified. ACTG2 expression was detected in all intestinal layers where smooth muscle cells are present in different stages of human development. No histopathological abnormalities were found in the patients. Using molecular modeling and MD simulations, we predicted that ACTG2 variants lead to significant changes to the protein function. This was confirmed by in vitro studies, which showed that the identified variants not only impair ACTG2 polymerization, but also contribute to reduced cell contractility. Taken together, our results confirm the involvement of ACTG2 in sporadic MMIHS, and bring new insights to MMIHS pathogenesis.

  14. Aggregation of Copper–Zinc Superoxide Dismutase in Familial and Sporadic ALS

    PubMed Central

    Chattopadhyay, Madhuri

    2009-01-01

    Abstract Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by the selective death of motor neurons. While the most common form of ALS is sporadic and has no known cause, a small subset of cases is familial because of underlying genetic mutations. The best-studies example of familial ALS is that caused by mutations in the protein copper–zinc superoxide dismutase. The formation of SOD1-rich inclusions in the spinal cord is an early and prominent feature of SOD1-linked familial ALS in human patients and animal models of this disease. These inclusions have been shown to consist of SOD1-rich fibrils, suggesting that the conversion of soluble SOD1 into amyloid fibrils may play an important role in the etiology of familial ALS. SOD1 is also present in inclusions found in spinal cords of sporadic ALS patients, allowing speculations to arise regarding a possible involvement of SOD1 in the sporadic form of this disease. We here review the recent research on the significance, causes, and mechanisms of SOD1 fibril formation from a biophysical perspective. Antioxid. Redox Signal. 11, 1603–1614. PMID:19271992

  15. Novel strain properties distinguishing sporadic prion diseases sharing prion protein genotype and prion type

    PubMed Central

    Cracco, Laura; Notari, Silvio; Cali, Ignazio; Sy, Man-Sun; Chen, Shu G.; Cohen, Mark L.; Ghetti, Bernardino; Appleby, Brian S.; Zou, Wen-Quan; Caughey, Byron; Safar, Jiri G.; Gambetti, Pierluigi

    2017-01-01

    In most human sporadic prion diseases the phenotype is consistently associated with specific pairings of the genotype at codon 129 of the prion protein gene and conformational properties of the scrapie PrP (PrPSc) grossly identified types 1 and 2. This association suggests that the 129 genotype favours the selection of a distinct strain that in turn determines the phenotype. However, this mechanism cannot play a role in the phenotype determination of sporadic fatal insomnia (sFI) and a subtype of sporadic Creutzfeldt-Jakob disease (sCJD) identified as sCJDMM2, which share 129 MM genotype and PrPSc type 2 but are associated with quite distinct phenotypes. Our detailed comparative study of the PrPSc conformers has revealed major differences between the two diseases, which preferentially involve the PrPSc component that is sensitive to digestion with proteases (senPrPSc) and to a lesser extent the resistant component (resPrPSc). We conclude that these variations are consistent with two distinct strains in sFI and sCJDMM2, and that the rarer sFI is the result of a variant strain selection pathway that might be favoured by a different brain site of initial PrPSc formation in the two diseases. PMID:28091514

  16. High-throughput screen detects calcium signaling dysfunction in typical sporadic autism spectrum disorder

    PubMed Central

    Schmunk, Galina; Nguyen, Rachel L.; Ferguson, David L.; Kumar, Kenny; Parker, Ian; Gargus, J. Jay

    2017-01-01

    Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders without any defined uniting pathophysiology. Ca2+ signaling is emerging as a potential node in the genetic architecture of the disorder. We previously reported decreased inositol trisphosphate (IP3)-mediated Ca2+ release from the endoplasmic reticulum in several rare monogenic syndromes highly comorbid with autism – fragile X and tuberous sclerosis types 1 and 2 syndromes. We now extend those findings to a cohort of subjects with sporadic ASD without any known mutations. We developed and applied a high throughput Fluorometric Imaging Plate Reader (FLIPR) assay to monitor agonist-evoked Ca2+ signals in human primary skin fibroblasts. Our results indicate that IP3 -mediated Ca2+ release from the endoplasmic reticulum in response to activation of purinergic receptors is significantly depressed in subjects with sporadic as well as rare syndromic forms of ASD. We propose that deficits in IP3-mediated Ca2+ signaling represent a convergent hub function shared across the spectrum of autistic disorders – whether caused by rare highly penetrant mutations or sporadic forms – and holds promise as a biomarker for diagnosis and novel drug discovery. PMID:28145469

  17. Erosive rhinitis resembling granulomatosis with polyangiitis (Wegener's granulomatosis) in an Anatolian shepherd dog.

    PubMed

    Böhm, Marlies; Basson, Sandra

    2015-04-21

    Granulomatosis with polyangiitis (Wegener's granulomatosis) is one of the idiopathicimmune-mediated small-vessel vasculitides described in humans which are characterised by the presence of circulating antineutrophil cytoplasmic antibodies. It most commonly involves capillaries, venules and arterioles of the ear, nose and throat, lungs and glomeruli. A case of destructive haemopurulent rhinitis associated with relapsing periods of pyrexia, lethargy and stiffness as well as generalised pulmonary infiltrates in a young Anatolian shepherd dog is presented that closely resembles granulomatosis with polyangiitis (GPA) as reported in humans. Perinuclear antineutrophil cytoplasmic antibodies (pANCA) were detected in the dog's serum. Signs resolved promptly and completely once immunosuppressive doses of prednisone were administered, and have not recurred. This is the first report onthe use of pANCA to investigate rhinitis in dogs. It is also, to the authors' knowledge, the first description of a relapsing haemopurulent lytic rhinitis in this species. The concurrent manifestations of erosive haemopurulent rhinitis, ground-glass opacities on pulmonary computed tomography, pyrexia and listlessness resemble GPA as described in humans.

  18. Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism

    PubMed Central

    Birla, S; Malik, E; Jyotsna, VP; Sharma, A

    2016-01-01

    Background and Objectives: Primary hyperparathyroidism (PHPT) can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein “menin.” We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. Materials and Methods: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. Results: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. Conclusions: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation. PMID:27366707

  19. PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas.

    PubMed

    Hafner, Christian; Schmiemann, Viola; Ruetten, Arno; Coras, Brigitte; Landthaler, Michael; Reifenberger, Julia; Vogt, Thomas

    2007-10-01

    Trichoblastomas are rare, benign tumors of the appendix in human skin. The histopathology comprises elements of basal cell carcinoma and trichoepithelioma with a variable degree of follicular differentiation. Both basal cell carcinoma and trichoepithelioma reveal alterations of PTCH, the human homolog of the Drosophila segment polarity patched gene. Furthermore, heterozygous PTCH knockout mice develop trichoblastoma-like tumors. This suggests an involvement of the PTCH gene in the pathogenesis of human trichoblastomas. However, trichoblastomas arising in nevus sebaceus did not show loss of heterozygosity at the PTCH locus (9q22.3) in a previous study. Sequencing of the PTCH gene and analysis of sporadic human trichoblastomas have not been performed yet. We therefore screened 10 sporadic trichoblastomas and 1 trichoblastoma arising within a nevus sebaceus for PTCH mutations. After microdissection of the tumors, single-strand conformational polymorphism (SSCP)/heteroduplex analysis of exons 2 to 23 of PTCH was performed, and polymerase chain reaction products with aberrant band patterns were sequenced. One trichoblastoma revealed a silent mutation at codon 562 in exon 12. Another trichoblastoma showed a somatic C > T single nucleotide substitution at codon 1,315 (exon 23), which was not present in corresponding normal epidermis. This mutation at codon 1,315 represents an already described PTCH germline polymorphism and results in a heterozygous Pro to Leu substitution in the tumor. The Pro/Leu polymorphism in germline is associated with a higher risk for breast cancer, but a potential contribution to the tumorigenesis of trichoblastoma is unknown. We detected no classical PTCH mutations in the investigated trichoblastomas. Our results indicate that PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas, in contrast to basal cell carcinomas and trichoepitheliomas. The genetic basis of this rare appendageal tumor remains elusive.

  20. Resembling a viper: implications of mimicry for conservation of the endangered smooth snake.

    PubMed

    Valkonen, Janne K; Mappes, Johanna

    2014-12-01

    The phenomenon of Batesian mimicry, where a palatable animal gains protection against predation by resembling an unpalatable model, has been a core interest of evolutionary biologists for 150 years. An extensive range of studies has focused on revealing mechanistic aspects of mimicry (shared education and generalization of predators) and the evolutionary dynamics of mimicry systems (co-operation vs. conflict) and revealed that protective mimicry is widespread and is important for individual fitness. However, according to our knowledge, there are no case studies where mimicry theories have been applied to conservation of mimetic species. Theoretically, mimicry affects, for example, frequency dependency of predator avoidance learning and human induced mortality. We examined the case of the protected, endangered, nonvenomous smooth snake (Coronella austriaca) that mimics the nonprotected venomous adder (Vipera berus), both of which occur in the Åland archipelago, Finland. To quantify the added predation risk on smooth snakes caused by the rarity of vipers, we calculated risk estimates from experimental data. Resemblance of vipers enhances survival of smooth snakes against bird predation because many predators avoid touching venomous vipers. Mimetic resemblance is however disadvantageous against human predators, who kill venomous vipers and accidentally kill endangered, protected smooth snakes. We found that the effective population size of the adders in Åland is very low relative to its smooth snake mimic (28.93 and 41.35, respectively).Because Batesian mimicry is advantageous for the mimic only if model species exist in sufficiently high numbers, it is likely that the conservation program for smooth snakes will fail if adders continue to be destroyed. Understanding the population consequences of mimetic species may be crucial to the success of endangered species conservation. We suggest that when a Batesian mimic requires protection, conservation planners should

  1. Cervical dystonia: about familial and sporadic cases in 88 patients.

    PubMed

    Camargo, Carlos Henrique F; Camargos, Sarah Teixeira; Becker, Nilson; Munhoz, Renato Puppi; Raskin, Salmo; Cardoso, Francisco Eduardo C; Teive, Hélio Afonso G

    2014-02-01

    Cervical dystonia (CD) affects the musculature of the neck in a focal way or associated to other parts of the body. The aim of this study was to identify clinical differences between patients with dystonia patients without family history and with family history (sporadic). Eighty-eight patients with CD were recruited in a Movement Disorders Clinic between June of 2008 and June of 2009. Only patients with no etiological diagnosis were accepted for analysis. The age of onset of symptoms was later in patients with focal and segmental dystonia than in patients with generalized dystonia (p<0.001). The severity of symptoms was higher in patients with sporadic dystonia than in familial patients (p<0.01). Generalized cases were more severe in patients with a family history (p<0.01). Sporadic patients had higher levels of pain than familial cases (p<0.05). We expect soon to present the results of genetic analyzes of these patients.

  2. Parameters of Sporadic E Layers and Transparency For Radio Waves

    NASA Astrophysics Data System (ADS)

    Bencze, P.

    Two frequency parameters of sporadic E layers are included into the scaling of verti- cal incidence ionograms, foEs and fbEs. They are called critical and blanketing fre- quency, respectively. On the basis of results of incoherent scatter measurements at mid-latitudes referring to the structure of sporadic E layers, the critical frequency is considered representing the mean electron density of patches imbedded in the back- ground electron density. The blanketing frequency would correspond to the back- ground electron density. Thus, the difference between critical and blanketing frequen- cies foEs-fbEs could indicate the transparency of sporadic E layers. Comparison of temporal and spatial variations of the transparency with corresponding variations of the vertical shear of the horizontal wind shows that the transparancy can be due to the wind-shear and patches would indicate eddies in the layer.

  3. Parkin Plays a Role in Sporadic Parkinson’s Disease

    PubMed Central

    Dawson, Ted M.; Dawson, Valina L.

    2014-01-01

    Background Parkinson’s Disease (PD) is a chronic progressive neurologic disorder, which affects approximately one million men and women in the U.S. alone. PD represents a heterogeneous disorder with common clinical manifestations and for the most part common neuropathological findings. Objective This short article reviews the role of the ubiquitin E3 ligase in sporadic PD. Methods The role of parkin in sporadic PD was reviewed by querying PubMed Results Parkin is inactivated in sporadic PD via S-nitrosylation, oxidative and dopaminergic stress, and phosphorylation by the stress activated kinase, c-Abl leading to the accumulation of AIMP2 and PARIS (ZNF746). Conclusion Strategies aimed at maintaining parkin in a catalytically active state or interfering with toxicity of AIMP2 and PARIS (ZNF746) offer new therapeutic opportunities. PMID:24029689

  4. Uterine Tumour Resembling Ovarian Sex Cord Tumour- A Rare Entity

    PubMed Central

    Ilhan, Tolgay Tuyan; Gül, Ayhan; Ugurluoglu, Ceyhan; Çelik, Çetin

    2016-01-01

    Uterine Tumour Resembling Ovarian Sex-Cord Tumours (UTROSCTs) are an extremely rare type of uterine body tumours arising from the endometrial stroma. Epidemiology, aetiology, pathogenesis, management and natural history of UTROSCTs are still a question of debate, as there is little available data in the literature. Although rare, the possibility of UTROSCTs should be kept in mind, when a patient presents with abnormal bleeding and an enlarged uterus. UTROSCTs appear dirty white/cream-coloured, gelatinous, well-circumscribed mass with smooth surface on macroscopic examination. We present a rare case of endometrial stromal tumour with sex-cord-like differentiation which was successfully treated by hysterectomy with bilateral salpingo-oophorectomy. The clinical manifestations, pathologic characteristics, diagnosis and management of these tumours are reviewed here. PMID:28208949

  5. Adenomyomatosis of the gallbladder resembling honeycomb in a child.

    PubMed

    Akçam, Mustafa; Buyukyavuz, Ilker; Ciriş, Metin; Eriş, Naim

    2008-09-01

    Adenomyomatosis of the gallbladder is believed to be an uncommon pathologic condition of the gallbladder in childhood. Only three pediatric cases have been described in the literature up to now. Honeycomb gallbladder has been described in two adult patients; no patients have been reported in childhood until now. To the best of our knowledge, we report here the first case of adenomyomatosis of the gallbladder which resembled honeycomb, in a 9-year-old girl presented with recurrent abdominal pain. The diagnosis was made by ultrasound, and confirmed by magnetic resonance cholangiopancreatography and finally cholecystectomy. In conclusion, ultrasound scanning performed more generally in children presenting with recurrent abdominal pain might lead to accurate diagnosis of adenomyomotosis of the gallbladder during childhood.

  6. Imperfect Batesian mimicry and the conspicuousness costs of mimetic resemblance.

    PubMed

    Speed, Michael P; Ruxton, Graeme D

    2010-07-01

    We apply signal detection methodology to make predictions about the evolution of Batesian mimicry. Our approach is novel in three ways. First, we applied a deterministic evolutionary modeling system that allows a large number of alternative mimetic morphs to coexist and compete. Second, we considered that there may be natural boundaries to phenotypic expression. Finally, we allowed increasing conspicuousness to impose an increasing detection cost on mimics. In some instances, the model predicts widespread variation in mimetic forms at evolutionary stability. In other situations, rather than a polymorphism the model predicts dimorphisms in which some prey were maximally cryptic and had minimal resemblance to the model, whereas many others were more conspicuous than the model. The biological implications of these results, particularly for our understanding of imperfect mimicry, are discussed.

  7. Microsatellite instability is rare in sporadic ovarian cancer

    SciTech Connect

    Chen, S.S.; Han, H.; Schwartz, P.E.

    1994-09-01

    Microsatellite instability was first demonstrated to be a common underlying mechanism in hereditary nonpolyposis colorectal cancer (HNPCC) and has recently been implicated in the development of several other human cancers. Although numerous genetic changes have been documented in ovarian cancer, their molecular bases are poorly understood. In investigating the molecular genetics of ovarian cancer, we analyzed twelve short tandem repeats that were amplified by PCR from DNA of 48 tumors and their corresponding lymphocyte samples. All of the 48 cases studied have no noticeable family history and, of them, 42 are epithelial (benign/borderline, 5; grade I, 4; GII, 4; GIII, 29) and 6 are nonepithelial. A microsatellite instability has been shown to be inversely correlated with the occurrence of allelic losses, half of those cases chosen have a fractional allele loss of {le}15 (median = .18 of 50 tumors tested for 86 loci from every chromosomal arm). The loci examined included eight dinucleotide repeats (D2S123, D9S104, D10S197, D11S904, D16S408, D16S421, D17S250, and D17S579), two trinucleotide repeats (DM and AR) and two tetranucleotide repeats (DXS981 and VWF). Despite the fact that HNPCC phenotype includes ovarian cancer and that microsatellite instability has been shown in one ovarian cancer from an HNPCC family, the allele sizes of 12 loci were found to be identical in all paired tumor and normal samples we studied except for one tumor at a single locus. The band shift displayed on polyacrylamide gel representing an additional allele of VWF was only observed in one grade III tumor. Our results are thus a strong indication that the alteration of microsatellite repeats may not play a major role in the development of sporadic ovarian cancer.

  8. Sporadic Creutzfeldt-Jakob disease--a review.

    PubMed

    Sharma, Stuti; Mukherjee, Madhurima; Kedage, Vivekananda; Muttigi, Manjunatha S; Rao, Anjali; Rao, Suryanarayana

    2009-01-01

    The objective is to study a patient with sporadic Creutzfeldt-Jakob disease (CJD). The patient, a 70-year-old woman with a history spanning over 1 month, with acute onset, progressive abnormal behavior, and cognitive decline with generalized asymmetrical myoclonic jerking, startle phenomenon, and cortical blindness, was referred to the hospital. On observation of clinical symptoms, metabolic and hematological investigations, MRI (magnetic resonance imaging), and EEG (electroencephalogram) were done. The clinical symptoms, MRI, and diagnostic EEG were suggestive of sporadic CJD. Other metabolic encephalopathies were ruled out. With sodium valproate and clonezepam, her myoclonic jerks improved slightly. As CJD is an incurable disease, no definitive treatment could be given.

  9. Necroptosis drives motor neuron death in models of both sporadic and familial ALS

    PubMed Central

    Re, Diane B.; Verche, Virginia Le; Yu, Changhao; Amoroso, Mackenzie W.; Politi, Kristin A.; Phani, Sudarshan; Ikiz, Burcin; Hoffmann, Lucas; Koolen, Martijn; Nagata, Tetsuya; Papadimitriou, Dimitra; Nagy, Peter; Mitsumoto, Hiroshi; Kariya, Shingo; Wichterle, Hynek; Henderson, Christopher E.; Przedborski, Serge

    2014-01-01

    SUMMARY Most cases of neurodegenerative disease are sporadic, hindering the use of genetic mouse models to analyze disease mechanisms. Focusing on the motor neuron (MN) disease amyotrophic lateral sclerosis (ALS) we therefore devised a fully humanized co-culture model composed of human adult primary sporadic ALS (sALS) astrocytes and human embryonic stem cell-derived MNs. The model reproduces the cardinal features of human ALS: sALS astrocytes, but not those from control patients, trigger selective death of MNs. The mechanisms underlying this non-cell-autonomous toxicity were investigated in both astrocytes and MNs. Although causal in familial ALS (fALS), SOD1 does not contribute to the toxicity of sALS astrocytes. Death of MNs triggered by either sALS or fALS astrocytes occurs through necroptosis, a form of programmed necrosis involving receptor-interacting protein 1 and the mixed lineage kinase domain-like protein. The necroptotic pathway therefore constitutes a novel potential therapeutic target for this incurable disease. PMID:24508385

  10. White matter involvement in sporadic Creutzfeldt-Jakob disease.

    PubMed

    Caverzasi, Eduardo; Mandelli, Maria Luisa; DeArmond, Stephen J; Hess, Christopher P; Vitali, Paolo; Papinutto, Nico; Oehler, Abby; Miller, Bruce L; Lobach, Irina V; Bastianello, Stefano; Geschwind, Michael D; Henry, Roland G

    2014-12-01

    Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P<0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter

  11. White matter involvement in sporadic Creutzfeldt-Jakob disease

    PubMed Central

    Mandelli, Maria Luisa; DeArmond, Stephen J.; Hess, Christopher P.; Vitali, Paolo; Papinutto, Nico; Oehler, Abby; Miller, Bruce L.; Lobach, Irina V.; Bastianello, Stefano; Geschwind, Michael D.; Henry, Roland G.

    2014-01-01

    Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P = 0.002), axial (P = 0.0003) and radial (P = 0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P < 0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P = 0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white

  12. LR11/SorLA Expression Is Reduced in Sporadic Alzheimer Disease but not in Familial Alzheimer Disease

    PubMed Central

    Dodson, Sara E.; Gearing, Marla; Lippa, Carol F.; Montine, Thomas J.; Levey, Allan I.; Lah, James J.

    2009-01-01

    LR11 is an ApoE receptor that is enriched in the brain. We have shown that LR11 is markedly downregulated in patients with sporadic Alzheimer disease (AD). This finding led us to explore whether reduced LR11 expression reflects a primary mechanism of disease or merely a secondary consequence of other AD-associated changes. Therefore, LR11 expression was assessed in a transgenic mouse model of AD and familial AD (FAD) brains. Immunohistochemistry and immunoblotting of LR11 in PS1/APP transgenic and wild-type mice indicated that LR11 levels are not affected by genotype or accumulation of amyloid pathology. LR11 expression was also evaluated based on immunoblotting and LR11 immunostaining intensity in human frontal cortex in controls, sporadic AD, and FAD, including cases with presenilin-1 (PS1) and presenilin-2 (PS2) mutations. Although LR11 was reduced in sporadic AD, there was no difference in protein level or staining intensity between control and FAD cases. The finding that LR11 expression is unaffected in both a mouse model of AD and autosomal-dominant forms of AD suggests that LR11 is not regulated by amyloid accumulation or other AD neuropathologic changes. We hypothesize that LR11 loss may be specific to sporadic AD and influence amyloid pathology through mechanisms independent of substrate–enzyme interactions regulated by FAD mutations. PMID:16957580

  13. Identification of preneoplastic lesions as mucin-depleted foci in patients with sporadic colorectal cancer.

    PubMed

    Sakai, Eiji; Morioka, Takamitsu; Yamada, Eiji; Ohkubo, Hidenori; Higurashi, Takuma; Hosono, Kunihiro; Endo, Hiroki; Takahashi, Hirokazu; Takamatsu, Reika; Cui, Changxu; Shiozawa, Manabu; Akaike, Makoto; Samura, Hironori; Nishimaki, Tadashi; Nakajima, Atsushi; Yoshimi, Naoki

    2012-01-01

    In experimental models, mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In humans, there is only one report of identification of MDF in patients with familial adenomatous polyposis and CRC; however, the histological characteristics of human MDF are not discussed extensively in the report. In the present study, colonic samples from 53 patients with sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were examined for the presence of aberrant crypt foci (ACF) by methylene blue staining. We classified MDF into two categories: flat-MDF and protruded-MDF (having the characteristics of both ACF and MDF). We found a total of 354, 41 and 19 colonic mucosal lesions with a mean multiplicity of 44, 38.9 and 66.9 crypts (ACF, flat-MDF and protruded-MDF, respectively). The density of MDF was 0.0082 lesions/cm(2) . The ACF identified in sporadic CRC patients corresponded to hyperplastic or non-dysplasic lesions. However, MDF identified in these patients corresponded to low-grade dysplasia. In addition, we found that Paneth cell metaplasia and inflammatory cell infiltration were specific histological features of MDF. These histological characteristics are reported to be associated with the development of CRC. Therefore, our results indicate that MDF might represent preneoplastic lesions in human colorectal carcinogenesis.

  14. A neural network dynamics that resembles protein evolution

    NASA Astrophysics Data System (ADS)

    Ferrán, Edgardo A.; Ferrara, Pascual

    1992-06-01

    We use neutral networks to classify proteins according to their sequence similarities. A network composed by 7 × 7 neurons, was trained with the Kohonen unsupervised learning algorithm using, as inputs, matrix patterns derived from the bipeptide composition of cytochrome c proteins belonging to 76 different species. As a result of the training, the network self-organized the activation of its neurons into topologically ordered maps, wherein phylogenetically related sequences were positioned close to each other. The evolution of the topological map during learning, in a representative computational experiment, roughly resembles the way in which one species evolves into several others. For instance, sequences corresponding to vertebrates, initially grouped together into one neuron, were placed in a contiguous zone of the final neural map, with sequences of fishes, amphibia, reptiles, birds and mammals associated to different neurons. Some apparent wrong classifications are due to the fact that some proteins have a greater degree of sequence identity than the one expected by phylogenetics. In the final neural map, each synaptic vector may be considered as the pattern corresponding to the ancestor of all the proteins that are attached to that neuron. Although it may be also tempting to link real time with learning epochs and to use this relationship to calibrate the molecular evolutionary clock, this is not correct because the evolutionary time schedule obtained with the neural network depends highly on the discrete way in which the winner neighborhood is decreased during learning.

  15. [Crohn's disease with the onset resembling systemic lupus erythematosus].

    PubMed

    Shimizu, T; Nishinarita, S; Son, K; Tomita, Y; Yoshihiro; Matsukawa; Kitamura, N; Horie, T; Baba, M; Hiranuma, M

    1999-06-01

    We described a 37-year-old man with Crohn's disease (CD) resembling systemic lupus erythematosus (SLE) at his disease onset. He was admitted to the municiple Akiru Hospital in October 1986 by fever, aphtous oral ulcerations, sore throat and polyarthralgia. Hematologic examination showed leukocytopenia, lymphocytopenia, positive tests for antinuclear antibody, anti-DNA antibody and LE cell phenomenon. He has had episodes of convulsion and conciousness loss of unknown etiology when he was 17 years old. The diagnosis of SLE was made, and oral medication of prednisolone was started. Several weeks later, most of symptoms and autoantibodies disappeared, although the oral aphtous ulcerations and leukocytopenia remained. In May 1987, he admitted to the other hospital because of bloody vomiting. Endoscopic examination showed the esophagial ulceration, and histology of biopsied-specimen was nonspecific esophagitis. The combination of prednisolone and oral cyclophosphamide or methotrexate was employed thereafter. However, the leukocytopenia, oral aphtous ulceration and esophagial ulceration continued in spite of these treatments. All the immunosuppressive treatment was stopped at March 1992. In October 1995, he admitted to our hospital because of body weight loss and continuous diarrhea with occasional bloody stool. Barium enema and endoscopic examination of the colon revealed the findings compatible with CD. The patient responded favorably to methylprednisolone pulse therapy followed by oral sulphasalazine. This case indicated that cases with inflammatory bowel diseases like CD could show similar clinical signs and symptoms to SLE, and in some cases of CD might satisfied the classification of criteria for SLE.

  16. Self-inflicted burns: a sporadic phenomenon.

    PubMed

    Rashid, Abid; Gowar, John P

    2004-12-01

    Self-inflicted burns are a regular cause of admission to burn units. Historically, a full moon has been associated with mental instability. Circadian rhythms and seasonal changes are known to influence human affect. Such cosmic effects, however, have not yet been studied for self-inflicted burns. In this regard, the results of a retrospective analysis of 184 self-inflicted burns admitted during a 20-year period to the Birmingham Burns Centre are presented. The analysis fails to show a connection between the timing of self-inflicted burns and cosmic events. Such incidents are random, not influenced by the day of the week, first or second half of the month, seasonal variation or phase of the lunar cycle.

  17. Ventricular Tachycardia and Resembling Acute Coronary Syndrome During Pheochromocytoma Crisis

    PubMed Central

    Li, Shi-jun; Wang, Tao; Wang, Lin; Pang, Zhan-qi; Ma, Ben; Li, Ya-wen; Yang, Jian; Dong, He

    2016-01-01

    Abstract Pheochromocytomas are neuroendocrine tumors, and its cardiac involvement may include transient myocardial dysfunction, acute coronary syndrome (ACS), and even ventricular arrhythmias. A patient was referred for evaluation of stuttering chest pain, and his electrocardiogram showed T-wave inversion over leads V1 to V4. Coronary angiography showed 90% stenosis in the mid-left anterior descending coronary artery (LAD), which was stented. Five days later, the patient had ventricular tachycardia, and severe hypertension, remarkable blood pressure fluctuation between 224/76 and 70/50 mm Hg. The patient felt abdominal pain and his abdominal ultrasound showed suspicious right adrenal gland tumor. Enhanced computed tomography of adrenal gland conformed that there was a tumor in right adrenal gland accompanied by an upset level of aldosterone. The tumor was removed by laparoscope, and the pathological examination showed pheochromocytoma. After the surgery, the blood pressure turned normal gradually. There was no T-wave inversion in lead V1-V4. Our case illustrates a rare pheochromocytoma presentation with a VT and resembling ACS. In our case, the serious stenosis in the mid of LAD could be explained by worsen the clinical course of myocardial ischemia or severe coronary vasospasm by the excessive amounts of catecholamines released from the tumor. Coronary vasospasm was possible because he had no classic coronary risk factors (e.g. family history and smoking habit, essential hypertension, hyperglycemia and abnormal serum lipoprotein, high body mass index). Thus, pheochromocytoma was missed until he revealed the association of his symptoms with abdominalgia. As phaeochromocytomas that present with cardiovascular complications can be fatal, it is necessary to screen for the disease when patients present with symptoms indicating catecholamine excess. PMID:27057898

  18. Familial resemblance for body composition measures: the HERITAGE Family Study.

    PubMed

    Rice, T; Daw, E W; Gagnon, J; Bouchard, C; Leon, A S; Skinner, J S; Wilmore, J H; Rao, D C

    1997-11-01

    A sex-specific familial correlation model was used to assess the heritable contributions to several measures of body composition in 86 sedentary white families participating in the HERITAGE Family Study. For this study, sedentary families were recruited, tested for a battery of measures, endurance exercise trained for 20 weeks, and remeasured. This sample is unique in that activity level was controlled for in these families at baseline measurement. In this report, three body composition variables measured at baseline were analyzed, two indexing adiposity (total subcutaneous fat based on eight skinfold measurements [SF8] and percent body fat measured by underwater weighing techniques [%BF]) and one assessing fat free mass ([FFM] derived from underwater weighing). The maximal heritabilities for SF8 (34%) and %BF (62%) were consistent with those reported in previous studies. There were no sex nor generation differences in the familial correlations, and the spouse correlation was significant, consistent with the hypothesis that the familial aggregation reflects genetic and familial environmental factors. However, the results for FFM were very different. The most parsimonious pattern of familial resemblance was consistent with mitochondrial inheritance (i.e., mother-offspring and sibling correlations were equal and were larger than those for spouse and father-offspring pairs). Under the mitochondrial hypothesis, 39% of the variance was accounted for by familial/genetic effects. However, under a nonmitochondrial hypothesis, which could not be ruled out, 65% of the FFM phenotypic variance was accounted for by familial/genetic factors. This high heritability level, as compared with results from previous studies, is consistent with the hypothesis that activity may constitute an important environmental determinant of FFM. These alternative hypotheses for FFM warrant further investigation using complex multilocus-multitrait segregation models, which allow for major genetic

  19. Metabolic disorders with clinical and radiologic features of sporadic Creutzfeldt-Jakob disease.

    PubMed

    Rosenbloom, Michael H; Tartaglia, M Carmela; Forner, Sven A; Wong, Katherine K; Kuo, Amy; Johnson, David Y; Colacurcio, Valerie; Andrews, Bret D; Miller, Bruce L; DeArmond, Stephen J; Geschwind, Michael D

    2015-04-01

    Two patients with metabolic disorders presented with clinical and radiologic features suggestive of sporadic Creutzfeldt-Jakob disease (sCJD). Case 1 was a 50-year-old man with rapid decline in cognitive, behavioral, and motor function following new-onset seizures. MRI was read as consistent with CJD, and he was referred for a treatment trial, but it was determined that he recently experienced rapid correction of hyponatremia resulting in extrapontine myelinolysis. Case 2 was a 66-year-old woman with poorly controlled diabetes mellitus who was found unconscious after a suspected insulin overdose. Examination showed altered mental status and neuroimaging was remarkable for cortical/striatal hyperintensities suggestive of sCJD. On autopsy, she had hypoglycemic/hypoxic nerve cell loss. Although characteristic MRI findings have high sensitivity and specificity for sCJD, potentially reversible metabolic disorders sometimes present rapidly and can resemble sCJD both clinically and radiologically. These cases highlight the importance of establishing a broad differential diagnosis when evaluating a patient with suspected sCJD.

  20. Progressive hereditary hearing impairment caused by a MYO6 mutation resembles presbyacusis.

    PubMed

    Oonk, A M M; Leijendeckers, J M; Lammers, E M; Weegerink, N J D; Oostrik, J; Beynon, A J; Huygen, P L M; Kunst, H P M; Kremer, H; Snik, A F M; Pennings, R J E

    2013-05-01

    Since deafness is the most common sensorineural disorder in humans, better understanding of the underlying causes is necessary to improve counseling and rehabilitation. A Dutch family with autosomal dominantly inherited sensorineural hearing loss was clinically and genetically assessed. The MYO6 gene was selected to be sequenced because of similarities with other, previously described DFNA22 phenotypes and a pathogenic c.3610C > T (p.R1204W) mutation was found to co-segregate with the disease. This missense mutation results in a flat configured audiogram with a mild hearing loss, which becomes severe to profound and gently to steeply downsloping later in life. The age-related typical audiograms (ARTA) constructed for this family resemble presbyacusis. Speech audiometry and results of loudness scaling support the hypothesis that the phenotype of this specific MYO6 mutation mimics presbyacusis.

  1. Extraocular muscle dysinnervation disorder resembling Duane retraction syndrome in a 9-month-old French Bulldog.

    PubMed

    Mari, Lorenzo; Blacklock, Benjamin T; Stavinohova, Renata; De Risio, Luisa

    2016-06-18

    A 9-month-old French Bulldog was presented with a chronic history of lateral strabismus and intermittent third eyelid protrusion in the left eye. The neuro-ophthalmological examination revealed mild ptosis of the left upper eyelid, mild lateral strabismus, and external ophthalmoparesis of the left eye. Retraction and ventral deviation of the left eye globe with protrusion of the third eyelid and elevation of the upper eyelid were elicited on attempted voluntary adduction of the left eye. Hematology, serum biochemistry, serology for infectious diseases, magnetic resonance of the head, and cerebrospinal fluid analysis did not reveal significant abnormalities. Forced duction test did not show signs of mechanical restriction in ocular motility. A suspected congenital cranial dysinnervation disorder resembling Duane retraction syndrome in humans was diagnosed based on the typical clinical signs and exclusion of structural abnormalities. The clinical signs remained stable for 9 months until the time of writing this report.

  2. Sporadic endolymphatic sac tumor – a diagnostic and therapeutic challenge

    PubMed Central

    Künzel, Julian; Agaimy, Abbas; Hornung, Joachim; Lell, Michael; Ganslandt, Oliver; Semrau, Sabine; Zenk, Johannes

    2014-01-01

    Endolymphatic sac tumor (ELST) is a rare low-grade locally aggressive neoplasm of the inner ear that may occur sporadically or in the setting of von Hippel-Lindau syndrome. We herein present a case of sporadic ELST in a 39-year-old man, treated using an interdisciplinary approach (surgery + radiotherapy), with a 10-year follow-up. The patient presented with hearing loss of sudden onset. The treatment of choice for ELST is radical tumor resection, which is associated with a good long-term prognosis. Remission may last for years, but there may be local recurrences, probably as a result of incomplete resection. Adjuvant radiotherapy is an option in case of recurrence and could be discussed after incomplete resection. The purpose of this report is to call attention to ELSTs, which are difficult to diagnose due to their rarity and variety of presentations. PMID:24966979

  3. Exact solutions for sporadic acceleration of cosmic rays

    NASA Technical Reports Server (NTRS)

    Cowsik, R.

    1985-01-01

    The steady state spectra of cosmic rays which are subject to a sporadic acceleration process, wherein the gain in energy in each encounter is a finite fraction of the particle energy are discussed. They are derived from a mathematical model which includes the possibility of energy dependent leakage of cosmic rays from the galaxy. Comparison with observations allows limits to be placed on the frequency and efficiency of such encounters.

  4. Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer

    PubMed Central

    Carethers, John M.; Jung, Barbara H.

    2015-01-01

    Sporadic colorectal cancer (CRC) is a somatic genetic disease in which pathogenesis is influenced by the local colonic environment and the patient’s genetic background. Consolidating the knowledge of genetic and epigenetic events that occur with initiation, progression, and metastasis of sporadic CRC has identified some biomarkers that might be utilized to predict behavior and prognosis beyond staging, and inform treatment approaches. Modern next generation sequencing of sporadic CRCs has confirmed prior identified genetic alterations, and has classified new alterations. Each patient’s CRC is genetically unique, propelled by 2 to 8 driver gene alterations that have accumulated within the CRC since initiation. Commonly observed alterations across sporadic CRCs have allowed classification into a: (1) hypermutated group that includes defective DNA mismatch repair with microsatellite instability (MSI) and POLE mutations in ~15%, containing multiple frameshifted genes and BRAFV600E; (2) non-hypermutated group with multiple somatic copy number alterations and aneuploidy in ~85%, containing oncogenic activation of KRAS and PIK3CA and mutation and loss of heterozygosity of tumor suppressor genes such as APC and TP53; (3) CpG Island Methylator Phenotype CRCs in ~20% that overlap greatly with MSI CRCs and some non-hypermutated CRCs; and (4) elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in ~60% that associates with metastatic behavior in both hypermutated and non-hypermutated groups. Components from these classifications are now used as diagnostic, prognostic and treatment biomarkers. Additional common biomarkers may come from genome-wide association studies and microRNAs among other sources, as well as from the unique alteration profile of an individual CRC to apply a precision medicine approach to care. PMID:26216840

  5. Application of dopplionograms to an understanding of sporadic E

    SciTech Connect

    Wright, J.W.

    1982-03-01

    The dopplionogram can be used to infer the vertical motion of plasma contours under some circumstances. In a sporadic E sequence, motions downward from above, and upward from below, are observed as the layer peak plasma density increases: this is interpreted as consistent with plasma convergence resulting from an east-west wind shear. When divergent motions occur, the layer is observed to dissipate and recede rapidly.

  6. Next generation sequencing in sporadic retinoblastoma patients reveals somatic mosaicism.

    PubMed

    Amitrano, Sara; Marozza, Annabella; Somma, Serena; Imperatore, Valentina; Hadjistilianou, Theodora; De Francesco, Sonia; Toti, Paolo; Galimberti, Daniela; Meloni, Ilaria; Cetta, Francesco; Piu, Pietro; Di Marco, Chiara; Dosa, Laura; Lo Rizzo, Caterina; Carignani, Giulia; Mencarelli, Maria Antonietta; Mari, Francesca; Renieri, Alessandra; Ariani, Francesca

    2015-11-01

    In about 50% of sporadic cases of retinoblastoma, no constitutive RB1 mutations are detected by conventional methods. However, recent research suggests that, at least in some of these cases, there is somatic mosaicism with respect to RB1 normal and mutant alleles. The increased availability of next generation sequencing improves our ability to detect the exact percentage of patients with mosaicism. Using this technology, we re-tested a series of 40 patients with sporadic retinoblastoma: 10 of them had been previously classified as constitutional heterozygotes, whereas in 30 no RB1 mutations had been found in lymphocytes. In 3 of these 30 patients, we have now identified low-level mosaic variants, varying in frequency between 8 and 24%. In 7 out of the 10 cases previously classified as heterozygous from testing blood cells, we were able to test additional tissues (ocular tissues, urine and/or oral mucosa): in three of them, next generation sequencing has revealed mosaicism. Present results thus confirm that a significant fraction (6/40; 15%) of sporadic retinoblastoma cases are due to postzygotic events and that deep sequencing is an efficient method to unambiguously distinguish mosaics. Re-testing of retinoblastoma patients through next generation sequencing can thus provide new information that may have important implications with respect to genetic counseling and family care.

  7. Formation of ionospheric sporadic E by atmospheric gravity waves

    NASA Astrophysics Data System (ADS)

    Didebulidze, Goderdzi; Dalakishvili, Giorgi; Matiashvili, Giorgi

    2016-07-01

    The atmospheric gravity waves (AGWs) significantly influence the behavior of the thermosphere ions/electrons. It is shown, that in the lower thermosphere when the background wind present, the AGWs evolving in this wind affect the heavy metallic ions vertical motions and can lead to their convergence into horizontal thin layers and consequently form ionosphere sporadic E (Es). For certain values of the velocity of horizontal back-ground wind, occurring in this region, the declined propagation of the AGWs in the mid-latitude lower thermosphere can cause formation multilayered sporadic E. The distances between such Es layers i.e. distance between locations of maximal ions/electrons densities occur is about one AGWs vertical wavelength. The observed phenomena like of sporadic E multilayered structures and Es layers downward motions are demonstrated by using 3-D numerical simulations describing Es formation by AGWs. The formation of quasi-periodic echoes like structures by AGWs evolving in the horizontal inhomogeneous wind and possibility of its ions/electrons density oscillations by smaller periods (smaller than Bunt-Väisälä period), which also is observed phenomena, is shown. Acknowledgements: This work has been supported by Shota Rustaveli National Science Foundation grant No 31/81.

  8. Stable and sporadic symbiotic communities of coral and algal holobionts

    PubMed Central

    Hester, Eric R; Barott, Katie L; Nulton, Jim; Vermeij, Mark JA; Rohwer, Forest L

    2016-01-01

    Coral and algal holobionts are assemblages of macroorganisms and microorganisms, including viruses, Bacteria, Archaea, protists and fungi. Despite a decade of research, it remains unclear whether these associations are spatial–temporally stable or species-specific. We hypothesized that conflicting interpretations of the data arise from high noise associated with sporadic microbial symbionts overwhelming signatures of stable holobiont members. To test this hypothesis, the bacterial communities associated with three coral species (Acropora rosaria, Acropora hyacinthus and Porites lutea) and two algal guilds (crustose coralline algae and turf algae) from 131 samples were analyzed using a novel statistical approach termed the Abundance-Ubiquity (AU) test. The AU test determines whether a given bacterial species would be present given additional sampling effort (that is, stable) versus those species that are sporadically associated with a sample. Using the AU test, we show that coral and algal holobionts have a high-diversity group of stable symbionts. Stable symbionts are not exclusive to one species of coral or algae. No single bacterial species was ubiquitously associated with one host, showing that there is not strict heredity of the microbiome. In addition to the stable symbionts, there was a low-diversity community of sporadic symbionts whose abundance varied widely across individual holobionts of the same species. Identification of these two symbiont communities supports the holobiont model and calls into question the hologenome theory of evolution. PMID:26555246

  9. Lightning-induced intensification of the ionospheric sporadic E layer.

    PubMed

    Davis, C J; Johnson, C G

    2005-06-09

    A connection between thunderstorms and the ionosphere has been hypothesized since the mid-1920s. Several mechanisms have been proposed to explain this connection, and evidence from modelling as well as various types of measurements demonstrate that lightning can interact with the lower ionosphere. It has been proposed, on the basis of a few observed events, that the ionospheric 'sporadic E' layer--transient, localized patches of relatively high electron density in the mid-ionosphere E layer, which significantly affect radio-wave propagation--can be modulated by thunderstorms, but a more formal statistical analysis is still needed. Here we identify a statistically significant intensification and descent in altitude of the mid-latitude sporadic E layer directly above thunderstorms. Because no ionospheric response to low-pressure systems without lightning is detected, we conclude that this localized intensification of the sporadic E layer can be attributed to lightning. We suggest that the co-location of lightning and ionospheric enhancement can be explained by either vertically propagating gravity waves that transfer energy from the site of lightning into the ionosphere, or vertical electrical discharge, or by a combination of these two mechanisms.

  10. A novel splice site associated polymorphism in the tuberous sclerosis 2 (TSC2) gene may predispose to the development of sporadic gangliogliomas.

    PubMed

    Platten, M; Meyer-Puttlitz, B; Blümcke, I; Waha, A; Wolf, H K; Nöthen, M M; Louis, D N; Sampson, J R; von Deimling, A

    1997-07-01

    The tuberous sclerosis 2 (TSC2) gene is thought to function as a growth suppressor in sporadic and TSC-associated hamartomas and tumors. Clusters of dysplastic glial cells are a common feature of cortical tubers and subependymal nodules in tuberous sclerosis patients. In an effort to identify TSC2 gene alterations in sporadic gliomas, we detected a novel polymorphism adjacent to the 3'splice site of intron 4. We evaluated the distribution of this variant allele in a series of 244 patients with glial tumors, including 55 gangliogliomas, 31 pilocytic astrocytomas (WHO grade I), 50 astrocytomas (WHO grades II and III), and 108 glioblastomas (WHO grade IV). The allelic distribution in the general population was estimated by examining 381 healthy blood donors. This rare allele appeared in the control population and in the patients with astrocytic gliomas with a virtually identical frequency (8.14%, and 8.20%, respectively). The frequency of the rare allele in gangliogliomas, however, was significantly higher (15.5%; p = 0.024). The fact that both gangliogliomas and cortical tubers in tuberous sclerosis contain neuronal and astrocytic elements and may resemble each other histologically suggests that the TSC2 gene may be involved in the development of these tumors. The rare allele of the TSC2 gene emerges as a candidate for a predisposing factor for the formation of sporadic gangliogliomas.

  11. Sporadic colon cancer murine models demonstrate the value of autoantibody detection for preclinical cancer diagnosis.

    PubMed

    Barderas, Rodrigo; Villar-Vázquez, Roi; Fernández-Aceñero, María Jesús; Babel, Ingrid; Peláez-García, Alberto; Torres, Sofía; Casal, J Ignacio

    2013-10-15

    Although autoantibody detection has been proposed for diagnosis of colorectal cancer, little is known about their initial production and development correlation with cancer progression. Azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice developed colon adenocarcinoma in the distal colon similar to human sporadic colon cancer. We assessed this model together with AOM and DSS-only models for their applicability to early detection of cancer. All AOM/DSS-treated mice produced autoantibodies to tumor-associated antigens analogous to those observed in human colon cancer patients. Autoantibody response was related to tumor antigen overexpression. Cancer autoantibodies were detected 21 days after starting treatment, when no malignant histopathological features were detectable, and they increased according to tumor progression. When carcinogenesis was induced separately by AOM or DSS, only those mice that developed malignant lesions produced significant levels of autoantibodies. These findings demonstrate that autoantibody development is an early event in tumorigenesis and validates its use for preclinical colon cancer diagnosis.

  12. Hereditary and Sporadic Forms of Aβ-Cerebrovascular Amyloidosis and Relevant Transgenic Mouse Models

    PubMed Central

    Kumar-Singh, Samir

    2009-01-01

    Cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the leptomeningeal and cerebral blood vessel walls, often causing secondary vascular degenerative changes. Although many kinds of peptides are known to be deposited as vascular amyloid, amyloid-β (Aβ)-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimer’s disease (AD) and Down’s syndrome. Moreover, Aβ-CAA is also associated with rare hereditary cerebrovascular amyloidosis due to mutations within the Aβ domain of the amyloid precursor protein (APP) such as Dutch and Flemish APP mutations. Genetics and clinicopathological studies on these familial diseases as well as sporadic conditions have already shown that CAA not only causes haemorrhagic and ischemic strokes, but also leads to progressive dementia. Transgenic mouse models based on familial AD mutations have also successfully reproduced many of the features found in human disease, providing us with important insights into the pathogenesis of CAA. Importantly, such studies have pointed out that specific vastopic Aβ variants or an unaltered Aβ42/Aβ40 ratio favor vascular Aβ deposition over parenchymal plaques, but higher than critical levels of Aβ40 are also observed to be anti-amyloidogenic. These data would be important in the development of therapies targeting amyloid in vessels. PMID:19468344

  13. Global Phylogenomic Analysis of Nonencapsulated Streptococcus pneumoniae Reveals a Deep-Branching Classic Lineage That Is Distinct from Multiple Sporadic Lineages

    PubMed Central

    Hilty, Markus; Wüthrich, Daniel; Salter, Susannah J.; Engel, Hansjürg; Campbell, Samuel; Sá-Leão, Raquel; de Lencastre, Hermínia; Hermans, Peter; Sadowy, Ewa; Turner, Paul; Chewapreecha, Claire; Diggle, Mathew; Pluschke, Gerd; McGee, Lesley; Köseoğlu Eser, Özgen; Low, Donald E.; Smith-Vaughan, Heidi; Endimiani, Andrea; Küffer, Marianne; Dupasquier, Mélanie; Beaudoing, Emmanuel; Weber, Johann; Bruggmann, Rémy; Hanage, William P.; Parkhill, Julian; Hathaway, Lucy J.; Mühlemann, Kathrin; Bentley, Stephen D.

    2014-01-01

    The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated S. pneumoniae (non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if non-Ec-Sp evolve sporadically, if they have high antibiotic nonsusceptiblity rates and a unique, specific gene content. Here, whole-genome sequencing of 131 non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multilocus sequences types (STs) ST344 (n = 39) and ST448 (n = 40). All ST344 and nine ST448 isolates had high nonsusceptiblity rates to β-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P = 0.005). In contrast, sporadic non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of PCV, non-Ec-Sp may become more prevalent. PMID:25480686

  14. Mutations in the RET proto-oncogene in sporadic pheochromocytomas

    SciTech Connect

    Thibodeau, S.N.; Lindor, N.M.; Honchel, R.

    1994-09-01

    Mutations in the RET proto-oncogene have recently been demonstrated in kindreds with Multiple Endocrine Neoplasia (MEN) types 2A and 2B. Both of these autosomal dominant disorders are characterized by the development of neoplasia in cell lines of neural crest origin, such as medullary throid carcinomas and pheochromocytomas. Individuals with MEN 2B have, in addition, ganglioneuromas of the lips, tongue and colon, a marfanoid habitus, and corneal nerve thickening. Approximately 90% of patients with MEN 2A have a germline mutation in exons 10 or 11, while 95% of patients with MEN 2B have a T{yields}C transition in codon 918 of exon 16. In this study, pheochromocytomas from 29 individuals who had no clinical evidence of MEN 2A or 2B (sporadic) were examined for the presence of either germline or somatic mutations in exons 10, 11, and 16 of the RET proto-oncogene. Of the 29 tumors examined, 3 (10%) were found to have a mutation in one of the three exons. One tumor had a G{yields}A transition in codon 609 (exon 10), another had a 6 bp deletion encompassing codons 632 & 633 (exon 11), and the final tumor had a T{yields}C transition in codon 918 (exon 16). These mutations were not found in the corresponding normal DNA from these individuals, indicating that the mutation were somatic in origin. Although we cannot exclude the possibility of mutations in other regions of the RET proto-oncogene, our data suggests that: (1) individuals presenting with apparently sporadic pheochromocytomas are not likely to have undiagnosed MEN 2A or 2B; and (2) somatic mutations in the RET proto-oncogene contribute to the process of tumorigenesis in a small percentage of sporadic pheochromocytomas.

  15. Sungrazing dust particles against the sporadic meteor background

    NASA Astrophysics Data System (ADS)

    Golubaev, A. V.

    2015-07-01

    From the results of the statistical study, the genetic relation between some meteors (from -5 m to +5 m ) of the sporadic background and the comets of the Kreutz, Marsden, and Kracht families has been revealed. The radiants of sporadic meteors are concentrated at the geocentric ecliptic latitudes 7°-10° northward and southward of the ecliptic. The radiants of the sungrazing meteoroids, that were detected on their heliocentric orbits "before" and "after" the perihelion passage, are concentrated in the elongation intervals of approximately 120°-165° and 20°-60° from the Sun, respectively. Each of the specified radiant regions, in its turn, breaks up into two groups. The group of radiants with elongations of about 30° and 155° from the Sun belongs to the Marsden and Kracht cometary families, while the group with 50° and 135°, to the Kreutz cometary family. In the distribution by perihelion distance, a sharp decrease of the number of observed dust particles with q < 0.08 AU was found. This corresponds to the heliocentric distances (20-30 R ⊙), where the production of microscopic dust due to sublimation of cometary nuclei, while approaching the Sun, terminates. The number of sporadic sungrazing meteoroids detected after their passage in the vicinity of the Sun is approximately 20 times smaller than the number of similar particles in the preperihelion part of the trajectory. This result is of special importance for studying the thermodesorption effect of meteoroids (i.e., the change in the content of chemical elements in meteoroids as a function of the perihelion distance).

  16. Resemblance and divergence: the "new" members of the genus Bordetella.

    PubMed

    Gross, Roy; Keidel, Kristina; Schmitt, Karin

    2010-08-01

    Bordetella pertussis, the etiological agent of whooping cough, belongs to the bacterial pathogens first described in the so-called golden era of microbiology more than 100 years ago. In the course of the following decades, several other closely related pathogens were described which are nowadays classified in the genus Bordetella together with B. pertussis. These are the human and animal pathogens B. parapertussis, B. bronchiseptica and B. avium which are of high medical or veterinary interest, and which, together with B. pertussis, are referred to as the "classical" Bordetella species. Only in the past 15 years, several additional species were classified in the genus, frequently isolated from patients with underlying disease, animals or from the environment. Very little is known about most of these bacteria. In the present review, the current knowledge about these "new" Bordetella species is briefly summarized.

  17. Most common 'sporadic' cancers have a significant germline genetic component.

    PubMed

    Lu, Yi; Ek, Weronica E; Whiteman, David; Vaughan, Thomas L; Spurdle, Amanda B; Easton, Douglas F; Pharoah, Paul D; Thompson, Deborah J; Dunning, Alison M; Hayward, Nicholas K; Chenevix-Trench, Georgia; Macgregor, Stuart

    2014-11-15

    Common cancers have been demarcated into 'hereditary' or 'sporadic' ('non-hereditary') types historically. Such distinctions initially arose from work identifying rare, highly penetrant germline mutations causing 'hereditary' cancer. While rare mutations are important in particular families, most cases in the general population are 'sporadic'. Twin studies have suggested that many 'sporadic' cancers show little or no heritability. To quantify the role of germline mutations in cancer susceptibility, we applied a method for estimating the importance of common genetic variants (array heritability, h(2)g) to twelve cancer types. The following cancers showed a significant (P < 0.05) array heritability: melanoma USA set h(2)g = 0.19 (95% CI = 0.01-0.37) and Australian set h(2)g = 0.30 (0.10-0.50); pancreatic h(2)g = 0.18 (0.06-0.30); prostate h(2)g = 0.81 (0.32-1); kidney h(2)g = 0.18 (0.04-0.32); ovarian h(2)g = 0.30 (0.18-0.42); esophageal adenocarcinoma h(2)g = 0.24 (0.14-0.34); esophageal squamous cell carcinoma h(2)g = 0.19 (0.07-0.31); endometrial UK set h(2)g = 0.23 (0.01-0.45) and Australian set h(2)g = 0.39 (0.02-0.76). Three cancers showed a positive but non-significant effect: breast h(2) g = 0.13 (0-0.56); gastric h(2)g = 0.11 (0-0.27); lung h(2)g = 0.10 (0-0.24). One cancer showed a small effect: bladder h(2)g = 0.01 (0-0.11). Among these cancers, previous twin studies were only able to show heritability for prostate and breast cancer, but we can now make much stronger statements for several common cancers which emphasize the important role of genetic variants in cancer susceptibility. We have demonstrated that several 'sporadic' cancers have a significant inherited component. Larger genome-wide association studies in these cancers will continue to find more loci, which explain part of the remaining polygenic component.

  18. Emotional Family Resemblances? Darwin's Contributions to a Theory of Emotions and Emotional Development.

    ERIC Educational Resources Information Center

    Hesse, Petra

    A family resemblance model of emotions is proposed which uses Darwin's discussion of emotions and Eleanor Rosch's and the philosopher Ludwig Wittgenstein's work on family resemblances. In Darwin's discussion of emotions, certain core features are thought to be widely shared by the members of the respective families of emotions, and more marginal…

  19. Reprogramming A375 cells to induced-resembled neuronal cells by structured overexpression of specific transcription genes

    PubMed Central

    Zhang, Hengzhu; Wei, Min; Jiang, Yangyang; Wang, Xiaodong; She, Lei; Yan, Zhengcun; Dong, Lun; Pang, Lujun; Wang, Xingdong

    2016-01-01

    Induced-resembled neuronal cells (irNCs) are generated by reprogramming human melanoma cells through the introduction of key transcription factors, providing novel concepts in the treatment of malignant tumor cells and making it possible to supply neural cells for laboratory use. In the present study, irNCs were derived from A375 cells by inducing the 'forced' overexpression of specific genes, including achaete-scute homolog 1 (Ascl1), neuronal differentiation factor 1 (Neurod1), myelin transcription factor 1 (Myt1), brain protein 2 (Brn2, also termed POU3F2) and human brain-derived neurotrophic factor (h-BDNF). irNCs induced from A375 cells express multiple neuronal markers and fire action potentials, exhibiting properties similar to those of motor neurons. The reprogramming procedure comprised reverse transcription-polymerase chain reaction and immunofluorescence staining; furthermore, electrophysiological profiling demonstrated the characteristics of the induced-resembled neurons. The present study obtained a novel type of human irNC from human melanoma, which secreted BDNF continuously, providing a model for neuron-like cells. Thus, irNCs offer promise in investigating various neural diseases by using neural-like cells derived directly from the patient of interest. PMID:27510459

  20. Familial and sporadic pancreatic cancer share the same molecular pathogenesis

    PubMed Central

    Norris, Alexis L.; Roberts, Nicholas J.; Jones, Siân; Wheelan, Sarah J.; Papadopoulos, Nickolas; Vogelstein, Bert; Kinzler, Kenneth W.; Hruban, Ralph H.; Klein, Alison P.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is nearly uniformly lethal, with a median overall survival in 2014 of only 6 months. The genetic progression of sporadic PDAC (SPC) is well established, with common somatic alterations in KRAS, p16/CDKN2A, TP53, and SMAD4/DPC4. Up to 10 % of all PDAC cases occur in families with two or more affected first-degree relatives (familial pancreatic cancer, FPC), but these cases do not appear to present at an obviously earlier age of onset. This is unusual because most familial cancer syndrome patients present at a substantially younger age than that of corresponding sporadic cases. Here we collated the reported age of onset for FPC and SPC from the literature. We then used an integrated approach including whole exomic sequencing, whole genome sequencing, RNA sequencing, and high density SNP microarrays to study a cohort of FPC cell lines and corresponding germline samples. We show that the four major SPC driver genes are also consistently altered in FPC and that each of the four detection strategies was able to detect the mutations in these genes, with one exception. We conclude that FPC undergoes a similar somatic molecular pathogenesis as SPC, and that the same gene targets can be used for early detection and minimal residual disease testing in FPC patients. PMID:25240578

  1. Sporadic Multifocal Venous Malformations of the Head and Neck

    PubMed Central

    Amato, Michael V.; Patel, Neha A.; Hu, Shirley; Pantelides, Harry

    2015-01-01

    Objective. To report a case of unusually widespread sporadic venous malformations of the head and neck associated with normal D-dimer levels and, due to the protean clinical manifestations and increased risk of coagulopathy of these lesions, to review their diagnosis and clinical management. Case Report. A 25-year-old man presented with a one-year history of intermittent right-sided neck swelling and tongue swelling. Physical exam revealed additional lesions present throughout the head and neck. There was no family history suggestive of heritable vascular malformations. Radiographic imaging demonstrated 15 lesions located in various tissue layers consistent with venous malformations. A coagulation screen showed a normal prothrombin time, activated partial thromboplastin time, international normalized ratio, D-dimer level, and fibrinogen level. It was determined that the patient was not at increased risk for intraoperative coagulopathy and preoperative heparin administration would not be necessary. The patient's buccal and tongue lesions were subsequently excised with no complications. The patient also underwent sclerotherapy evaluation for his neck mass. Conclusion. This case describes a unique presentation of sporadic multifocal venous malformations. It also emphasizes the importance of prompt diagnosis and workup when multiple venous malformations are present to prevent morbidity during surgical excision secondary to intravascular coagulopathy. PMID:26483982

  2. Is familial papillary thyroid microcarcinoma more aggressive than sporadic form?

    PubMed Central

    Lee, Cho Rok; Park, Seulkee; Kang, Sang-Wook; Lee, Jandee; Jeong, Jong Ju; Chung, Woong Youn; Park, Cheong Soo

    2017-01-01

    Purpose With the increasing incidence of papillary thyroid microcarcinoma (PTMC), familial papillary thyroid microcarcinoma (FPTMC) is now recognized more frequently. However, the biological behavior of FPTMC is poorly understood. The aim of this study was to investigate the prevalence of FPTMC and its biological aggressiveness. Methods Between March 2006 and July 2010, 2,414 patients underwent primary surgical therapy for PTMC and 149 (6.2%) were further classified as FPTMC. To determine the biological aggressiveness of FPTMC, we compared the clinicopathological features and prognosis between FPTMC and sporadic PTMC (SPTMC). Results The male-to-female ratio was higher in FPTMC than in sporadic papillary thyroid microcarcinoma (SPTMC: 1:4.5 vs. 1:7.2, P = 0.041). The central lymph node (LN) metastasis rate was significantly higher in FPTMC than in SPTMC (36.2% vs. 24.2%, P = 0.002). The local recurrence rate was also higher in FPTMC than in SPTMC (4.5% vs. 0.6%, P < 0.001). We identified familial occurrence in 6.2% of cases of PTMC. FPTMC is associated with a high rate of central LN metastasis and local recurrence. Conclusion These findings suggest that close follow-up can be beneficial in FPTMC patients to detect local recurrence. PMID:28289666

  3. Molecular pathogenesis and targeted therapy of sporadic pancreatic neuroendocrine tumors.

    PubMed

    Capurso, Gabriele; Archibugi, Livia; Delle Fave, Gianfranco

    2015-08-01

    Over the past few years, knowledge regarding the molecular pathology of sporadic pancreatic neuroendocrine tumors (PNETs) has increased substantially, and a number of targeted agents have been tested in clinical trials in this tumor type. For some of these agents there is a strong biological rationale. Among them, the mammalian target of rapamycin inhibitor Everolimus and the antiangiogenic agent Sunitinib have both been approved for the treatment of PNETs. However, there is lack of knowledge regarding biomarkers able to predict their efficacy, and mechanisms of resistance. Other angiogenesis inhibitors, such as Pazopanib, inhibitors of Src, Hedgehog or of PI3K might all be useful in association or sequence with approved agents. On the other hand, the clinical significance, and potential for treatment of the most common mutations occurring in sporadic PNETs, in the MEN-1 gene and in ATRX and DAXX, remains uncertain. The present paper reviews the main molecular changes occurring in PNETs and how they might be linked with treatment options.

  4. Early detection of sporadic pancreatic cancer: summative review.

    PubMed

    Chari, Suresh T; Kelly, Kimberly; Hollingsworth, Michael A; Thayer, Sarah P; Ahlquist, David A; Andersen, Dana K; Batra, Surinder K; Brentnall, Teresa A; Canto, Marcia; Cleeter, Deborah F; Firpo, Matthew A; Gambhir, Sanjiv Sam; Go, Vay Liang W; Hines, O Joe; Kenner, Barbara J; Klimstra, David S; Lerch, Markus M; Levy, Michael J; Maitra, Anirban; Mulvihill, Sean J; Petersen, Gloria M; Rhim, Andrew D; Simeone, Diane M; Srivastava, Sudhir; Tanaka, Masao; Vinik, Aaron I; Wong, David

    2015-07-01

    Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.

  5. Permanent changes in sporadic E layers over fortaleza, Brazil

    NASA Astrophysics Data System (ADS)

    Abdu, M. A.; Batista, I. S.; MacDougall, J.; Sobral, J. H. A.; Muralikrishna, P.

    1997-01-01

    Data available on sporadic E layers in ionograms, from 1975 to 1995 over Fortaleza (38 deg W, 4 deg S) in Brazil are analysed as an extension of a previous study to examine permanent changes in the occurrence characteristics of the different types of E_s layers. The so called q type E_s produced by plasma instability (type II) process of the equatorial electrojet and the other types of E_s produced by wind/wind shear mechanism are studied separately. The results show that while the occurrence of the former variety steadily decreased during the period of analysis, the latter type showed marked increases. These characteristics are shown to be associated mainly with the steady drift of the magnetic equator to northward of Fortaleza at a rate of ~ 0.2 degree per year. The long term trends are, however, modulated by solar activity cycle in F_10.7 flux. Also there is a suggestion of a possible effect from the June 1991 Pinatubo volcanic eruption. The competing roles of the neutral winds and electric fields in the formation of the low latitude sporadic E layer is demonstrated.

  6. A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis

    PubMed Central

    Yu, Haiyang; Artomov, Mykyta; Brähler, Sebastian; Stander, M. Christine; Shamsan, Ghaidan; Sampson, Matthew G.; White, J. Michael; Kretzler, Matthias; Jain, Sanjay; Winkler, Cheryl A.; Mitra, Robi D.; Daly, Mark J.; Shaw, Andrey S.

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease. Multiple factors including chemical toxicity, inflammation, and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small fraction of patients with a family history of FSGS. Variants of apolipoprotein L1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility. Here, we used sequencing to investigate whether genetics plays a role in the majority of FSGS cases that are identified as primary or sporadic FSGS and have no known cause. Given the limited number of biopsy-proven cases with ethnically matched controls, we devised an analytic strategy to identify and rank potential candidate genes and used an animal model for validation. Nine candidate FSGS susceptibility genes were identified in our patient cohort, and three were validated using a high-throughput mouse method that we developed. Specifically, we introduced a podocyte-specific, doxycycline-inducible transactivator into a murine embryonic stem cell line with an FSGS-susceptible genetic background that allows shRNA-mediated targeting of candidate genes in the adult kidney. Our analysis supports a broader role for genetic susceptibility of both sporadic and familial cases of FSGS and provides a tool to rapidly evaluate candidate FSGS-associated genes. PMID:26901816

  7. Seroepidemiology and risk factors for sporadic norovirus/Mexico strain.

    PubMed

    Peasey, Anne E; Ruiz-Palacios, Guillermo M; Quigley, Maria; Newsholme, William; Martinez, Julia; Rosales, Gustavo; Jiang, Xi; Blumenthal, Ursula J

    2004-06-01

    Risk factors associated with transmission of sporadic norovirus (NV; formerly Norwalk-like virus)/Mexico strain were identified in a seroepidemiological study conducted in rural Mexico. Acquisition of Mexico strain IgA antibodies was age-related; 34% of 1-4-year-olds were seropositive, compared with 81% of adults (P<.001). After 12 months, 42% of 1-4-year-olds showed a seroresponse to Mexico strain, compared with 27% of adults (P<.01). Personal and domestic hygiene measures, such as hand washing, general cleanliness of the mother's clothing, and the type of room assigned for cooking were significantly associated with odds of a seroresponse. For infants, having a dog in or near the home was a risk factor for seroresponse (P<.01), whereas, for older children, the mother's involvement in agricultural activities was a risk factor (P<.001). This study provides initial evidence of risk factors associated with sporadic NV infection. Data indicate some similarities to risk factors associated with outbreaks of NV infection.

  8. Trace amounts of sporadically reappearing HCV RNA can cause infection

    PubMed Central

    Veerapu, Naga Suresh; Park, Su-Hyung; Tully, Damien C.; Allen, Todd M.; Rehermann, Barbara

    2014-01-01

    Successful hepatitis C virus (HCV) treatment is defined as the absence of viremia 6 months after therapy cessation. We previously reported that trace amounts of HCV RNA, below the sensitivity of the standard clinical assay, can reappear sporadically in treatment responders. Here, we assessed the infectivity of this RNA and infused 3 chimpanzees sequentially at 9-week intervals with plasma or PBMCs from patients who tested positive for trace amounts of HCV RNA more than 6 months after completing pegylated IFN-α/ribavirin therapy. A fourth chimpanzee received HCV RNA–negative plasma and PBMCs from healthy blood donors. The 3 experimental chimpanzees, but not the control chimpanzee, generated HCV-specific T cell responses against nonstructural and structural HCV sequences 6–10 weeks after the first infusion of patient plasma and during subsequent infusions. In 1 chimpanzee, T cell responses declined, and this animal developed high-level viremia at week 27. Deep sequencing of HCV demonstrated transmission of a minor HCV variant from the first infusion donor that persisted in the chimpanzee for more than 6 months despite undetectable systemic viremia. Collectively, these results demonstrate that trace amounts of HCV RNA, which appear sporadically in successfully treated patients, can be infectious; furthermore, transmission can be masked in the recipient by an extended eclipse phase prior to establishing high-level viremia. PMID:25003189

  9. Comparing Characteristics of Sporadic and Outbreak-Associated Foodborne Illnesses, United States, 2004–2011

    PubMed Central

    Ebel, Eric D.; Cole, Dana; Travis, Curtis C.; Klontz, Karl C.; Golden, Neal J.; Hoekstra, Robert M.

    2016-01-01

    Outbreak data have been used to estimate the proportion of illnesses attributable to different foods. Applying outbreak-based attribution estimates to nonoutbreak foodborne illnesses requires an assumption of similar exposure pathways for outbreak and sporadic illnesses. This assumption cannot be tested, but other comparisons can assess its veracity. Our study compares demographic, clinical, temporal, and geographic characteristics of outbreak and sporadic illnesses from Campylobacter, Escherichia coli O157, Listeria, and Salmonella bacteria ascertained by the Foodborne Diseases Active Surveillance Network (FoodNet). Differences among FoodNet sites in outbreak and sporadic illnesses might reflect differences in surveillance practices. For Campylobacter, Listeria, and Escherichia coli O157, outbreak and sporadic illnesses are similar for severity, sex, and age. For Salmonella, outbreak and sporadic illnesses are similar for severity and sex. Nevertheless, the percentage of outbreak illnesses in the youngest age category was lower. Therefore, we do not reject the assumption that outbreak and sporadic illnesses are similar. PMID:27314510

  10. ERKed by LRRK2: A cell biological perspective on hereditary and sporadic Parkinson’s disease

    PubMed Central

    Verma, Manish; Steer, Erin K.; Chu, Charleen T.

    2014-01-01

    The leucine rich repeat kinase 2 (LRRK2/dardarin) is implicated in autosomal dominant familial and sporadic Parkinson’s disease (PD); mutations in LRRK2 account for up to 40% of PD cases in some populations. LRRK2 is a large protein with a kinase domain, a GTPase domain, and multiple potential protein interaction domains. As such, delineating the functional pathways for LRRK2 and mechanisms by which PD-linked variants contribute to age-related neurodegeneration could result in pharmaceutically tractable therapies. A growing number of recent studies implicate dysregulation of mitogen activated protein kinases 3 and 1 (also known as ERK1/2) as possible downstream mediators of mutant LRRK2 effects. As these master regulators of growth, differentiation, neuronal plasticity and cell survival have also been implicated in other PD models, a set of common cell biological pathways may contribute to neuronal susceptibility in PD. Here, we review the literature on several major cellular pathways impacted by LRRK2 mutations – autophagy, microtubule/cytoskeletal dynamics, and protein synthesis – in context of potential signaling crosstalk involving the ERK1/2 and Wnt signaling pathways. Emerging implications for calcium homeostasis, mitochondrial biology and synaptic dysregulation are discussed in relation to LRRK2 interactions with other PD gene products. It has been shown that substantia nigra neurons in human PD and Lewy body dementia patients exhibit cytoplasmic accumulations of ERK1/2 in mitochondria, autophagosomes and bundles of intracellular fibrils. Both experimental and human tissue data implicate pathogenic changes in ERK1/2 signaling in sporadic, toxin-based and mutant LRRK2 settings, suggesting engagement of common cell biological pathways by divergent PD etiologies. PMID:24225420

  11. Conspicuousness, color resemblance, and toxicity in geographically diverging mimicry: The pan-Amazonian frog Allobates femoralis.

    PubMed

    Amézquita, Adolfo; Ramos, Óscar; González, Mabel Cristina; Rodríguez, Camilo; Medina, Iliana; Simões, Pedro Ivo; Lima, Albertina Pimentel

    2017-01-09

    Predation risk is allegedly reduced in Batesian and Müllerian mimics, because their coloration resembles the conspicuous coloration of unpalatable prey. The efficacy of mimicry is thought to be affected by variation in the unpalatability of prey, the conspicuousness of the signals, and the visual system of predators that see them. Many frog species exhibit small colorful patches contrasting against an otherwise dark body. By measuring toxicity and color reflectance in a geographically variable frog species and the syntopic toxic species, we tested whether unpalatability was correlated with between-species color resemblance and whether resemblance was highest for the most conspicuous components of coloration pattern. Heterospecific resemblance in colorful patches was highest between species at the same locality, but unrelated to concomitant variation in toxicity. Surprisingly, resemblance was lower for the conspicuous femoral patches compared to the inconspicuous dorsum. By building visual models, we further tested whether resemblance was affected by the visual system of model predators. As predicted, mimic-model resemblance was higher under the visual system of simulated predators compared to no visual system at all. Our results indicate that femoral patches are aposematic signals and support a role of mimicry in driving phenotypic divergence or mimetic radiation between localities.

  12. Sporadic impact flashes on the Moon and their implications

    NASA Astrophysics Data System (ADS)

    Trigo-Rodriguez, J. M.; Ortiz, J. L.; Llorca, J.; Santos-Sanz, P.

    The systematic impact flash survey that we carried out between 2001 and 2004 resulted in the first unambiguous detection of lunar sporadic impact flashes (Ortiz et al., 2006) and already allowed us to estimate the impact rate of objects on Earth as a function of their incoming energy under the assumption of a certain range of luminous efficiencies of the impact processes. Some present unknown parameters can be constrained in the future by monitoring impact flashes associated with meteoroid streams exhibiting a wide range of impact angles and energies. Here we further investigate some implications of the sporadic impact flashes detected so far and in particular we focus on whether the SMART-1 impact flash can give additional constraints on the luminous efficiency applicable to sporadic impacts, in order to derive more accurate impact rates on Earth. We have compared our derived impact fluxes with those obtained by Ceplecha (2001) and Brown et al. (2002) and we conclude that the present flux in the observed energy range would be underestimated. Finally, we conclude that the large lunar surface coverage and increasing sensitivity of modern video cameras makes this a powerful method to estimate terrestrial impact rates of large bodies that are statistically difficult to be detected from more limited atmospheric coverages characteristic of terrestrial networks. REFERENCES Brown, P., Spalding, R. E., Revelle, D. O., Tagliaferri, E., Worden, S. P. 2002. The flux of small near-Earth objects colliding with the Earth. Nature 420, 294-296. Ceplecha Z. (2001) in Collisional processes in the solar system, eds. Mikhail Ya. Marov and Hans Rickman, Astrophysics and Space Science library, Vol. 261, Dordrecht, Kluwer Academic Publishers, 35 - 50. Ortiz J.L., F.J. Aceituno, J.A. Quesada, J. Aceituno, M. Fernández, P. Santos-Sanz, J.M. Trigo-Rodríguez, J. Llorca, F.J. Martín-Torres, P. Montañés-Rodríguez, E. Pallé (2006) Icarus, in press.

  13. The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome.

    PubMed Central

    Lyon, M F; Peters, J; Glenister, P H; Ball, S; Wright, E

    1990-01-01

    The X chromosome-linked scurfy (sf) mutant of the mouse is recognized by the scaliness of the skin from which the name is derived and results in death of affected males at about 3-4 weeks of age. Consideration of known man-mouse homologies of the X chromosome prompted hematological studies, which have shown that the blood is highly abnormal. The platelet and erythrocyte counts are both reduced and become progressively lower relative to normal as the disease progresses. There is gastrointestinal bleeding, and most animals appear to die of severe anemia. By contrast, the leukocyte count is consistently raised. Some animals showed signs of infection but it is not yet clear whether there is immunodeficiency. Other features include the scaly skin and apparently reduced lateral growth of the skin, conjunctivitis, and diarrhea in some animals. The mutant resembles Wiskott-Aldrich syndrome in man, which is characterized by thrombocytopenia, eczema, diarrhea, and immunodeficiency. The loci of the human and mouse genes lie in homologous segments of the X chromosome, although apparently in somewhat different positions relative to other gene loci. Scurfy differs from Wiskott-Aldrich syndrome in that scurfy males are consistently hypogonadal. Images PMID:2320565

  14. Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis.

    PubMed

    Augustin, Iris; Gross, Julia; Baumann, Daniel; Korn, Claudia; Kerr, Grainne; Grigoryan, Tamara; Mauch, Cornelia; Birchmeier, Walter; Boutros, Michael

    2013-08-26

    Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains poorly understood. To analyze the role of Wnt proteins in this process, we created a conditional knockout allele of the Wnt cargo receptor Evi/Gpr177/Wntless and studied mice that lacked Evi expression in the epidermis. We found that K14-Cre, Evi-LOF mice lost their hair during the first hair cycle, showing a reddish skin with impaired skin barrier function. Expression profiling of mutant and wild-type skin revealed up-regulation of inflammation-associated genes. Furthermore, we found that Evi expression in psoriatic skin biopsies is down-regulated, suggesting that Evi-deficient mice developed skin lesions that resemble human psoriasis. Immune cell infiltration was detected in Evi-LOF skin. Interestingly, an age-dependent depletion of dendritic epidermal T cells (DETCs) and an infiltration of γδ(low) T cells in Evi mutant epidermis was observed. Collectively, the described inflammatory skin phenotype in Evi-deficient mice revealed an essential role of Wnt secretion in maintaining normal skin homeostasis by enabling a balanced epidermal-dermal cross talk, which affects immune cell recruitment and DETC survival.

  15. Multisystemic Eosinophilia Resembling Hypereosinophilic Syndrome in a Colony-Bred Owl Monkey (Aotus vociferans)

    PubMed Central

    Gozalo, Alfonso S; Rosenberg, Helene F; Elkins, William R; Montoya, Enrique J; Weller, Richard E

    2009-01-01

    In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naïve, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney, adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate. PMID:19476722

  16. Alzheimer's disease modeling: ups, downs, and perspectives for human induced pluripotent stem cells.

    PubMed

    Wojda, Urszula; Kuznicki, Jacek

    2013-01-01

    Major breakthroughs are required to win the war against the increasing threat of Alzheimer's disease. Until now, however, despite enormous efforts and funds, effective therapies are lacking, and adequate models for drug validation are still unavailable. In this article, we review the available animal and cellular models of different features of human Alzheimer's disease and critically evaluate their usefulness for understanding the mechanisms of the disease. The majority of the presently used models are based on the amyloid-β and hyperphosphorylated tau hypothesis, which resembles features of familial Alzheimer's disease. Unfortunately, these models offer limited help for understanding the pathomechanisms of the early stages of sporadic Alzheimer's disease. Thus, new models are needed to discover ways to treat or delay the onset of Alzheimer's disease, and we discuss the prospects for such desperately needed models, including human induced pluripotent stem cells and in silico brain models.

  17. Sporadic radio emission of the Sun in the decametre range

    NASA Astrophysics Data System (ADS)

    Melnik, Valentin N.; Konovalenko, Alexander A.; Rucker, Helmut O.; Lecacheux, Alain

    2007-08-01

    Results of the last observations of solar sporadic radio emission at the UTR-2 radio telescope (Kharkov, Ukraine) at the frequencies 10 - 30 MHz are presented. The use of new backend facilities, the DSP and 60-channel spectrometer, allows us to obtain data with time resolution up to 2 ms and frequency resolution of 12 kHz in the continuous frequency band 12 MHz. Usual Type III bursts, Type IIIb bursts, U- and J-bursts in the decameter range are discussed. Special attention is paid to detection and analysis of Type II bursts and their properties, newly discovered fine time structures of Type III bursts, Type III-like bursts, s-bursts, new observational features of drift pair bursts, and ‘absorption’ bursts.

  18. Sporadic Radio Emission of the Sun in the Decameter Range

    NASA Astrophysics Data System (ADS)

    Mel'Nik, V. N.; Konovalenko, A. A.; Rucker, H. O.; Lecacheux, A.

    2006-08-01

    Results of the last observations of solar sporadic radio emission on the UTR-2 radio telescope (Kharkov, Ukraine) at the frequencies 10-30MHz are presented. Using of new back-end facilities, the DSP and 60-channel spectrometer, allows obtaining data with time resolution up to 2 ms and frequency resolution 12 kHz in the continuous frequency band 12MHz. Usual Type III bursts, type III-b bursts, U- and J- bursts in the decameter range are discussed. Especial attention is paid to detection and analysis of Type II bursts and their properties, first found fine time structures of Type III bursts, Type III-like bursts, s-bursts, new observational features of drift pair bursts, "absorption" burst.

  19. Ion Mass Spectrometer for Sporadic-E Rocket Experiments

    NASA Technical Reports Server (NTRS)

    Heelis, R. A.; Earle, G. D.; Pfaff, Robert

    2000-01-01

    NASA grant NAG5-5086 provided funding for the William B. Hanson Center for Space Sciences at the University of Texas at Dallas (UTD) to design, fabricate, calibrate, and ultimately fly two ion mass spectrometer instruments on a pair of sounding rocket payloads. Drs. R.A. Heelis and G.D. Earle from UTD were co-investigators on the project. The principal investigator for both rocket experiments was Dr. Robert Pfaff of the Goddard Space Flight Center. The overall project title was "Rocket/Radar Investigation of Lower Ionospheric Electrodynamics Associated with Intense Mid-Latitude Sporadic-E Layers". This report describes the overall objectives of the project, summarizes the instrument design and flight experiment details, and presents representative data obtained during the flights.

  20. [Virological and clinical features of patients with sporadic hepatitis C].

    PubMed

    Tang, Z; Wang, Y; Yu, Z; Yang, D; Hao, L

    1997-06-01

    In this study, the transmission route in 16 sporadic hepatitis C (SHC) patients was investigated. Three of them were surgeons who had often had occupational needlestick accidents, another 3 had close household contact with their spouses who had been diagnosed as chronic posttransfusion viral hepatitis C (PTHC), and the remaining 5 had potential parenteral exposure such as tooth extraction, injection or inoculation and so on. Five patients with SHC didn't have such history, their transmission route was not determined. Our result showed a lower viremia level in patients with SHC when compared to PTHC patients (the serum dilutions for HCV RNA detection was 10-100 times in the former and 100-10000 times in the latter. P<0.01). Only 1 patient with SHC was anti-HCV positive. Comparing to PTHC, the patients with SHC in our study had milder liver demage and lower ALT levels, and most of them (10/16) were symptomless.

  1. A sporadic third layer in the ionosphere of Mars.

    PubMed

    Pätzold, M; Tellmann, S; Häusler, B; Hinson, D; Schaa, R; Tyler, G L

    2005-11-04

    The daytime martian ionosphere has been observed as a two-layer structure with electron densities that peak at altitudes between about 110 and 130 kilometers. The Mars Express Orbiter Radio Science Experiment on the European Mars Express spacecraft observed, in 10 out of 120 electron density profiles, a third ionospheric layer at altitude ranges of 65 to 110 kilometers, where electron densities, on average, peaked at 0.8 x 10(10) per cubic meter. Such a layer has been predicted to be permanent and continuous. Its origin has been attributed to ablation of meteors and charge exchange of magnesium and iron. Our observations imply that this layer is present sporadically and locally.

  2. Apoptosis signals in sporadic amyotrophic lateral sclerosis: an immunocytochemical study.

    PubMed

    Embacher, N; Kaufmann, W A; Beer, R; Maier, H; Jellinger, K A; Poewe, W; Ransmayr, G

    2001-11-01

    Sporadic amyotrophic lateral sclerosis (sALS) is a neurodegenerative disorder of unknown cause characterized by selective loss of both upper and lower motor neurons. Whether neuronal death in sALS is due to apoptosis has so far not been clarified. In this study, the expression and distribution patterns of pro- and anti-apoptotic bcl-2 family members as well as the executioner caspase-3 were investigated in post-mortem CNS tissue of eight sALS patients and seven age-matched controls. Sparse motor neurons were immunoreactive for bcl-2, bax, bak, and CM1 on serial sections through the spinal cord and motor cortex of individual sALS patients and controls. However, there was no obvious difference in the numbers of immunoreactive (IR) neurons between the two groups. The study did not find evidence for apoptosis as a major mechanism of motor neuronal cell death in sALS.

  3. Double sporadic metal layers as observed by colocated Fe and Na lidars at Wuhan, China

    NASA Astrophysics Data System (ADS)

    Wang, Xiaodong; Yi, Fan; Huang, Kaiming

    2017-02-01

    In this paper, we report a set of double sporadic layer events observed by Fe and Na lidars over Wuhan, China. The two sporadic metal layers above normal layer were named as upper and middle sporadic metal layers, respectively. In these events, the upper, middle, and normal Fe layers presented altitude separately. There were nine double sporadic Fe events observed in 163 nights during 2010-2013. Eight of the nine events were observed in summer. The maximum ratios of peak density for upper and middle sporadic Fe layers to normal Fe layer were up to 375% and 225%, respectively. The peak altitudes of upper (middle) sporadic Fe layers were in the range of 102-107 km (95-98.5 km). The double sporadic Fe layers lasted more than 2 h. Interestingly, we found that density enhancement occurred simultaneously in upper, middle, and normal Fe layers on two events. On the nine Fe events, there existed five nights of colocated Na lidar observations. We found that double sporadic Na and Fe layers simultaneously appeared. They presented similar structures, altitudes, and temporal variations in all five compared events. A little different from Fe, the middle sporadic Na layer was not separated from Na main layer maybe for the wide altitude range of Na main layer. The ratios of upper (middle) sporadic Fe and Na peak values were in the range of 6.6-52 (0.57-6.58). While the exact formation mechanism responsible for double sporadic metal layers is still unclear, some possible explanations and corresponding observations are discussed.

  4. Whole-Exome Sequencing Studies of Nonhereditary (Sporadic) Parathyroid Adenomas

    PubMed Central

    Newey, Paul J.; Nesbit, M. Andrew; Rimmer, Andrew J.; Attar, Moustafa; Head, Rosie T.; Christie, Paul T.; Gorvin, Caroline M.; Stechman, Michael; Gregory, Lorna; Mihai, Radu; Sadler, Greg; McVean, Gil; Buck, David

    2012-01-01

    Context: Genetic abnormalities, such as those of multiple endocrine neoplasia type 1 (MEN1) and Cyclin D1 (CCND1) genes, occur in <50% of nonhereditary (sporadic) parathyroid adenomas. Objective: To identify genetic abnormalities in nonhereditary parathyroid adenomas by whole-exome sequence analysis. Design: Whole-exome sequence analysis was performed on parathyroid adenomas and leukocyte DNA samples from 16 postmenopausal women without a family history of parathyroid tumors or MEN1 and in whom primary hyperparathyroidism due to single-gland disease was cured by surgery. Somatic variants confirmed in this discovery set were assessed in 24 other parathyroid adenomas. Results: Over 90% of targeted exons were captured and represented by more than 10 base reads. Analysis identified 212 somatic variants (median eight per tumor; range, 2–110), with the majority being heterozygous nonsynonymous single-nucleotide variants that predicted missense amino acid substitutions. Somatic MEN1 mutations occurred in six of 16 (∼35%) parathyroid adenomas, in association with loss of heterozygosity on chromosome 11. However, no other gene was mutated in more than one tumor. Mutations in several genes that may represent low-frequency driver mutations were identified, including a protection of telomeres 1 (POT1) mutation that resulted in exon skipping and disruption to the single-stranded DNA-binding domain, which may contribute to increased genomic instability and the observed high mutation rate in one tumor. Conclusions: Parathyroid adenomas typically harbor few somatic variants, consistent with their low proliferation rates. MEN1 mutation represents the major driver in sporadic parathyroid tumorigenesis although multiple low-frequency driver mutations likely account for tumors not harboring somatic MEN1 mutations. PMID:22855342

  5. Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease.

    PubMed Central

    Mathews, P. M.; Cataldo, A. M.; Kao, B. H.; Rudnicki, A. G.; Qin, X.; Yang, J. L.; Jiang, Y.; Picciano, M.; Hulette, C.; Lippa, C. F.; Bird, T. D.; Nochlin, D.; Walter, J.; Haass, C.; Lévesque, L.; Fraser, P. E.; Andreadis, A.; Nixon, R. A.

    2000-01-01

    BACKGROUND: Mutations in the presenilin proteins cause early-onset, familial Alzheimer's disease (FAD). MATERIALS AND METHODS: We characterized the cellular localization and endoproteolysis of presenilin 2 (PS2) and presenilin 1 (PS1) in brains from 25 individuals with presenilin-mutations causing FAD, as well as neurologically normal individuals and individuals with sporadic Alzheimer's disease (AD). RESULTS: Amino-terminal antibodies to both presenilins predominantly decorated large neurons. Regional differences between the broad distributions of the two presenilins were greatest in the cerebellum, where most Purkinje cells showed high levels of only PS2 immunoreactivity. PS2 endoproteolysis in brain yielded multiple amino-terminal fragments similar in size to the PS1 amino-terminal fragments detected in brain. In addition, two different PS2 amino-terminal antibodies also detected a prominent 42 kDa band that may represent a novel PS2 form in human brain. Similar to PS1 findings, neither amino-terminal nor antiloop PS2 antibodies revealed substantial full-length PS2 in brain. Immunocytochemical examination of brains from individuals with the N141I PS2 mutation or eight different PS1 mutations, spanning the molecule from the second transmembrane domain to the large cytoplasmic loop domain, revealed immunodecoration of no senile plaques and only neurofibrillary tangles in the M139I PS1 mutation stained with PS1 antibodies. CONCLUSIONS: Overall presenilin expression and the relative abundance of full-length and amino-terminal fragments in presenilin FAD cases were similar to control cases and sporadic AD cases. Thus, accumulation of full-length protein or other gross mismetabolism of neither PS2 nor PS1 is a consequence of the FAD mutations examined. PMID:11126202

  6. Risk factors associated with sporadic salmonellosis in adults: a case-control study.

    PubMed

    Ziehm, D; Dreesman, J; Campe, A; Kreienbrock, L; Pulz, M

    2013-02-01

    In order to identify and assess recent risk factors for sporadic human infections with Salmonella enterica, we conducted a case-control study in Lower Saxony, Germany. The data collection was based on standardized telephone interviews with 1017 cases and 346 controls aged >14 years. Odds ratios were calculated in single-factor and multi-factor analyses for Salmonella cases and two different control groups, i.e. population controls and controls with rotavirus infection. Multi-factor analysis revealed associations between sporadic Salmonella infections for two exposures by both sets of controls: consumption of raw ground pork [adjusted odds ratio (aOR) 2·38, 95% confidence interval (CI) 1·27-4·44] and foreign travel (aOR 2·12, 95% CI 1·00-4·52). Other exposures included consumption of food items containing eggs (aOR 1·43, 95% CI 0·80-2·54), consumption of chicken meat (aOR 1·77, 95% CI 1·26-2·50), outdoor meals/barbecues (aOR 3·96, 95% CI 1·41-11·12) and taking gastric acidity inhibitors (aOR 2·42, 95% CI 1·19-4·92), all were significantly associated with respect to one of the two control groups. The impact of consuming food items containing eggs or chicken meat was lower than expected from the literature. This might be a consequence of Salmonella control programmes as well as increased public awareness of eggs and chicken products being a risk factor for salmonellosis. Efforts to reduce Salmonella infections due to raw pork products should be intensified.

  7. Staphylococcus pseudintermedius expresses surface proteins that closely resemble those from Staphylococcus aureus.

    PubMed

    Geoghegan, Joan A; Smith, Emma J; Speziale, Pietro; Foster, Timothy J

    2009-09-18

    Staphylococcus pseudintermedius is a commensal of dogs that is implicated in the pathogenesis of canine pyoderma. This study aimed to determine if S. pseudintermedius expresses surface proteins resembling those from Staphylococcus aureus and to characterise them. S. pseudintermedius strain 326 was shown to adhere strongly to purified fibrinogen, fibronectin and cytokeratin 10. It adhered to the alpha-chain of fibrinogen which, along with binding to cytokeratin 10, is the hallmark of clumping factor B of S. aureus, a surface protein that is in part responsible for colonisation of the human nares. Ligand-affinity blotting with cell-wall extracts demonstrated that S. pseudintermedius 326 expressed a cell-wall anchored fibronectin binding protein which recognised the N-terminal 29kDa fragment. The ability to bind fibronectin is an important attribute of pathogenic S. aureus and is associated with the ability of S. aureus to colonise skin of human atopic dermatitis patients. S. pseudintermedius genomic DNA was probed with labelled DNA amplified from the serine-aspartate repeat encoding region of clfA of S. aureus. This probe hybridised to a single SpeI fragment of S. pseudintermedius DNA. In the cell-wall extract of S. pseudintermedius 326, a 180kDa protein was discovered which bound to fibrinogen by ligand-affinity blotting and reacted in a Western blot with antibodies raised against the serine-aspartate repeat region of ClfA and the B-repeats of SdrD of S. aureus. It is proposed that this is an Sdr protein with B-repeats that has an A domain that binds to fibrinogen. Whether it is the same protein that binds cytokeratin 10 is not clear.

  8. RESEMBLANCES BETWEEN THE ELECTROMOTOR VARIATIONS OF RHYTHMICALLY REACTING LIVING AND NON-LIVING SYSTEMS.

    PubMed

    Lillie, R S

    1929-09-20

    1. The electromotor variations of pure iron wires, arranged to react rhythmically with nitric acid, are recorded and described. 2. Resemblances between these variations and those of rhythmically reacting living tissues (especially the heart) are pointed out and discussed.

  9. Histopathology and clinical outcome of NF1-associated vs. sporadic malignant peripheral nerve sheath tumors.

    PubMed

    Hagel, Christian; Zils, Ulrich; Peiper, Matthias; Kluwe, Lan; Gotthard, Stefan; Friedrich, Reinhard E; Zurakowski, David; von Deimling, Andreas; Mautner, Victor Felix

    2007-04-01

    The differences in the clinical course and histopathology of sporadic and neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNST) were investigated retrospectively. The collective comprised 38 NF1 patients and 14 sporadic patients. NF1 patients were significantly younger at diagnosis (p<0.001) and had a significantly shorter survival time than sporadic patients (median survival 17 months vs. 42 months, Breslow p<0.05). The time interval to local recurrence and metastatic spread was also significantly shorter in NF1 patients (9.4 months vs. 30.0 months, p<0.01; 9.1 months vs. 33.2 months, p<0.001, respectively). In patients with the original histopathological data available (22 NF1 patients, 14 sporadic cases), NF1-associated MPNST showed a significantly higher cellularity compared to sporadic tumors (p<0.001) whereas sporadic MPNST featured a significantly higher pleomorphism (p<0.01). Most importantly, while histopathological variables correlated with French Fédération Nationale des Centres de Lutte Contre le Cancer grading in sporadic MPNST, this was not the case for NF1-associated tumors. The differences between NF1-associated and sporadic MPNST in regard to the clinical course and histopathology may reflect some fundamental differences in biology and pathomechanism of the two tumor groups. Our findings indicate the necessity for a separate grading scheme which takes into account the genetic background in NF1 patients.

  10. Who Resembles Whom? Mimetic and Coincidental Look-Alikes among Tropical Reef Fishes

    PubMed Central

    Robertson, D. Ross

    2013-01-01

    Studies of mimicry among tropical reef-fishes usually give little or no consideration to alternative explanations for behavioral associations between unrelated, look-alike species that benefit the supposed mimic. I propose and assess such an alternative explanation. With mimicry the mimic resembles its model, evolved to do so in response to selection by the mimicry target, and gains evolved benefits from that resemblance. In the alternative, the social-trap hypothesis, a coincidental resemblance of the model to the “mimic” inadvertently attracts the latter to it, and reinforcement of this social trapping by learned benefits leads to the “mimic” regularly associating with the model. I examine three well known cases of supposed aggressive mimicry among reef-fishes in relation to nine predictions from these hypotheses, and assess which hypothesis offers a better explanation for each. One case, involving precise and complex morphological and behavioral resemblance, is strongly consistent with mimicry, one is inconclusive, and one is more consistent with a social-trap based on coincidental, imprecise resemblance. Few cases of supposed interspecific mimicry among tropical reef fishes have been examined in depth, and many such associations may involve social traps arising from generalized, coincidental resemblance. Mimicry may be much less common among these fishes than is generally thought. PMID:23372795

  11. Estrogen receptor β-deficient female mice develop a bladder phenotype resembling human interstitial cystitis

    PubMed Central

    Imamov, Otabek; Yakimchuk, Konstantin; Morani, Andrea; Schwend, Thomas; Wada-Hiraike, Osamu; Razumov, Sergei; Warner, Margaret; Gustafsson, Jan-Åke

    2007-01-01

    Interstitial cystitis/painful bladder syndrome is a disease seen mostly in women, and symptoms tend to be worse premenopausally or during ovulation. The four cardinal symptoms of interstitial cystitis/painful bladder syndrome are bladder pain, urgency, frequency, and nocturia. Estrogen has been implicated in the etiology of this disease, but the role of the two estrogen receptors (ER), ERα and ERβ, has not been investigated. We found that, in the bladders of WT mice, ERβ is expressed in the basal cell layer of the urothelium. Bladders of male ERβ−/− mice were intact and morphologically indistinguishable from those of their WT littermates. However, in female ERβ−/− mice, there was ulceration and atrophy of bladder urothelium concomitant with infiltration of γδ T cells concentrated in the areas of atrophy and shedding of urothelium. The data support the idea that activated γδ T cells are causing the damage to the urothelium. The hyperactivity of T cells may be because of an imbalance between ERα and ERβ signaling in female ERβ−/− mice. Our data suggest that reduced ERβ signaling might have a role in the pathogenesis of interstitial cystitis, and ERβ could be a candidate for a target of medical therapy. PMID:17522255

  12. Gene Expression Analysis of Sporadic Early-Onset Rectal Adenocarcinoma

    PubMed Central

    Nfonsam, V; Xu, W; Koblinski, J; Jandova, J

    2016-01-01

    Background Overall declines in incidence of rectal cancer (RC) in patients older than 50 years have been mostly attributed to improvement in treatment modalities and introduction of age-based screening. Recent studies, however, have shown a rise in the incidence of RC in patients younger than 50 years. The etiology of early-onset (EO) RC is not well understood. The aim of this study is to elucidate the molecular features of (EO) RC and show its uniqueness compared to late-onset (LO) disease. Methods Two cohorts of patients with sporadic RC were identified. Tumors and matching non-involved tissues from six (EO) RC patients (< 50 years) and six (LO) RC patients (>65 years) were obtained from Pathology archives. Deparaffinized tissues were macro-dissected from FFPE sections, RNA isolated and used for expression profiling of 770 cancer related genes representing 13 canonical pathways. Statistical analysis was performed using the Gene Expression R-script module within the nCounter software v2.6. A gene was considered to be above background if the average count for the target gene was greater than the average counts for the eight negative control genes and if the P value of the t-test was less than 0.05. Results When we compared rectal tumors to non-involved rectal tissues, changes in expression levels of 171 genes were statistically significant in early-onset group and 151 genes in late-onset group. Further comparative gene expression analysis between early- and late-onset rectal tumors normalized to their matching non-involved tissues revealed that changes in expression of 65 genes were unique to early-onset rectal tumors with 16 genes being up- and 49 genes down-regulated using the cutoff criteria of expression levels difference >2 fold and p-value <0.01. At the pathway level, MAPK signaling was the most deregulated pathway in early-onset rectal tumors compared to PI3K-AKT signaling pathway being the most deregulated in late-onset rectal tumors. Conclusions Results of

  13. Association studies in late onset sporadic Alzheimer`s disease

    SciTech Connect

    Goate, A.M.; Lendon, C.; Talbot, C.

    1994-09-01

    Alzheimer`s disease (AD) is characterized by an adult onset progressive dementia and the presence of numerous plaques and tangles within the brain at autopsy. The senile plaques are composed of a proteinaceous core surrounded by dystrophic neurites. The major protein component of the core is {beta}-amyloid but antibodies to many other proteins bind to senile plaques, e.g., antibodies to apolioprotein E (ApoE) and to {alpha}1-antichymotrypsin (AACT). Genetic studies have implicated mutations within the {beta}-amyloid precursor protein gene as the cause of AD in a small number of early onset AD families. More recently, assocition studies in late onset AD have demonstrated a positive association between ApoE-{epsilon}4 and AD. We report evidence for a negative association between ApoE-{epsilon}2 and AD in a large sample of sporadic late onset AD cases and matched controls supporting the role of ApoE in the etiology of AD. Ninety-three patients with sporadic AD (average age = 75 years, s.d. 8 yrs.) and 67 normal controls from the same ethnic background (age = 77 yrs., s.d. 10 yrs.) were recruited through the patient registry of the Washington University Alzheimer`s Disease Research Center. We found a statistically significant increase in ApoE-{epsilon}4 allele frequency in patients compared with controls ({chi}{sup 2}=7.75, 1 d.f., one tailed p=0.0027) and a significant decrease in {epsilon}2 allele frequency (Fisher`s exact test, one tailed p=0.0048), whereas the decreased frequency of {epsilon}3 in the patient groups was not statistically significant. Allele {epsilon}2 conferred a strong protective effect in our sample, with the odds ratio for AD for subjects possessing this allele being 0.08 (85% confidence interval 0.01-0.69). Similar studies using a polymorphism within the AACT gene showed no association with alleles at this locus in the entire AD sample or in AD cases homozygous for ApoE-{epsilon}3.

  14. Impact of sporadic reporting of poultry Salmonella serovars from selected developing countries.

    PubMed

    Barbour, Elie K; Ayyash, Danielle B; Alturkistni, Wafa; Alyahiby, Areej; Yaghmoor, Soonham; Iyer, Archana; Yousef, Jehad; Kumosani, Taha; Harakeh, Steve

    2015-01-15

    This review documents the sporadic reporting of poultry Salmonella serovars in South Africa, Egypt, Indonesia, India, and Romania, five countries selected based on the importance of their distribution in different regions of the world and their cumulative significant population size of 1.6 billion. South Africa reported contamination of its poultry carcasses by S. Hadar, S. Blockley, S. Irumu, and S. Anatum. Results from Egypt showed that S. Enteritidis and S. Typhimurium were predominant in poultry along with other non-typhoid strains, namely S. Infantis, S. Kentucky, S. Tsevie, S. Chiredzi, and S. Heidelberg. In Indonesia, the isolation of Salmonella Typhi was the main focus, while other serovars included S. Kentucky, S. Typhimurium, and S. Paratyhi C. In India, S. Bareilly was predominant compared to S. Enteritidis, S. Typhimurium, S. Paratyphi B, S. Cerro, S. Mbandaka, S. Molade, S. Kottbus, and S. Gallinarum. Romania reported two Salmonella serovars in poultry that affect humans, namely S. Enteritidis and S. Typhimurium, and other non-typhoid strains including S. Infantis, S. Derby, S. Colindale, S. Rissen, S. Ruzizi, S. Virchow, S. Brandenburg, S. Bredeney, S. Muenchen, S. Kortrijk, and S. Calabar. The results showed the spread of different serovars of Salmonella in those five developing countries, which is alarming and emphasizes the urgent need for the World Health Organization Global Foodborne Infections Network (WHO-GFN) to expand its activities to include more strategic participation and partnership with most developing countries in order to protect poultry and humans from the serious health impact of salmonellosis.

  15. Brain sterol dys-regulation in sporadic AD and MCI: Relationship to heme oxygenase-1

    PubMed Central

    Hascalovici, Jacob R.; Vaya, Jacob; Khatib, Soliman; Holcroft, Christina A.; Zukor, Hillel; Song, Wei; Arvanitakis, Zoe; Bennett, David A.; Schipper, Hyman M.

    2009-01-01

    The objective of this study was to ascertain the impact of aging and Alzheimer disease (AD) on brain cholesterol (CH), CH precursors and oxysterol homeostasis. Altered CH metabolism and up-regulation of heme oxygenase-1 (HO-1) are characteristic of AD-affected neural tissues. We recently determined that HO-1 over-expression suppresses total CH levels by augmenting liver X receptor-mediated CH efflux and enhances oxysterol formation in cultured astroglia. Lipids and proteins were extracted from post-mortem human frontal cortex derived from subjects with sporadic AD, mild cognitive impairment (MCI) and no cognitive impairment (NCI; n=17 per group) enrolled in the Religious Orders Study, an ongoing clinical-pathologic study of aging and AD. ELISA was used to quantify human HO-1 protein expression from brain tissue and GC-MS to quantify total CH, CH precursors and relevant oxysterols. The relationships of sterol/oxysterol levels to HO-1 protein expression and clinical/demographic variables were determined by multivariable regression and non-parametric statistical analyses. Decreased CH, increased oxysterol and increased CH precursors concentrations in the cortex correlated significantly with HO-1 levels in MCI and AD, but not NCI. Specific oxysterols correlated with disease state, increasing neuropathological burden, neuropsychological impairment and age. A model featuring compensated and de-compensated states of altered sterol homeostasis in MCI and AD are presented based on the current data set and our earlier in vitro work. PMID:19522732

  16. HER2 Analysis in Sporadic Thyroid Cancer of Follicular Cell Origin

    PubMed Central

    Ruggeri, Rosaria M.; Campennì, Alfredo; Giuffrè, Giuseppe; Giovanella, Luca; Siracusa, Massimiliano; Simone, Angela; Branca, Giovanni; Scarfì, Rosa; Trimarchi, Francesco; Ieni, Antonio; Tuccari, Giovanni

    2016-01-01

    The Epidermal Growth Factor Receoptor (EGFR) family member human epidermal growth factor receptor 2 (HER2) is overexpressed in many human epithelial malignancies, representing a molecular target for specific anti-neoplastic drugs. Few data are available on HER2 status in differentiated thyroid cancer (DTC). The present study was aimed to investigate HER2 status in sporadic cancers of follicular cell origin to better clarify the role of this receptor in the stratification of thyroid cancer. By immunohistochemistry and fluorescence in-situ hybridization, HER2 expression was investigated in formalin-fixed paraffin-embedded surgical specimens from 90 DTC patients, 45 follicular (FTC) and 45 papillary (PTC) histotypes. No HER2 immunostaining was recorded in background thyroid tissue. By contrast, overall HER2 overexpression was found in 20/45 (44%) FTC and 8/45 (18%) PTC, with a significant difference between the two histotypes (p = 0.046). Five of the six patients who developed metastatic disease during a median nine-year follow-up had a HER2-positive tumor. Therefore, we suggest that HER2 expression may represent an additional aid to identify a subset of patients who are characterized by a worse prognosis and are potentially eligible for targeted therapy. PMID:27929428

  17. Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis

    PubMed Central

    2013-01-01

    Background Potential biomarkers to aid diagnosis and therapy need to be identified for Amyotrophic Lateral Sclerosis, a progressive motor neuronal degenerative disorder. The present study was designed to identify the factor(s) which are differentially expressed in the cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (SALS; ALS-CSF), and could be associated with the pathogenesis of this disease. Results Quantitative mass spectrometry of ALS-CSF and control-CSF (from orthopaedic surgical patients undergoing spinal anaesthesia) samples showed upregulation of 31 proteins in the ALS-CSF, amongst which a ten-fold increase in the levels of chitotriosidase-1 (CHIT-1) was seen compared to the controls. A seventeen-fold increase in the CHIT-1 levels was detected by ELISA, while a ten-fold elevated enzyme activity was also observed. Both these results confirmed the finding of LC-MS/MS. CHIT-1 was found to be expressed by the Iba-1 immunopositive microglia. Conclusion Elevated CHIT-1 levels in the ALS-CSF suggest a definitive role for the enzyme in the disease pathogenesis. Its synthesis and release from microglia into the CSF may be an aligned event of neurodegeneration. Thus, high levels of CHIT-1 signify enhanced microglial activity which may exacerbate the process of neurodegeneration. In view of the multifold increase observed in ALS-CSF, it can serve as a potential CSF biomarker for the diagnosis of SALS. PMID:24295388

  18. Chlamydia pecorum: fetal and placental lesions in sporadic caprine abortion.

    PubMed

    Giannitti, Federico; Anderson, Mark; Miller, Myrna; Rowe, Joan; Sverlow, Karen; Vasquez, Marce; Cantón, Germán

    2016-03-01

    Chlamydial abortion in small ruminants is usually associated with Chlamydia abortus infection. Although Chlamydia pecorum has been detected in aborted ruminants and epidemiological data suggests that C. pecorum is abortigenic in these species, published descriptions of lesions in fetuses are lacking. This work describes fetoplacental lesions in a caprine abortion with C. pecorum infection, and further supports the abortigenic role of C. pecorum in ruminants. A 16-month-old Boer goat aborted twin fetuses at ~130 days of gestation. Both fetuses (A and B) and the placenta of fetus A were submitted for postmortem examination and diagnostic workup. At autopsy, the fetuses had moderate anasarca, intermuscular edema in the hindquarters (A), and brachygnathia and palatoschisis (B). In the placenta, the cotyledons were covered by yellow fibrinosuppurative exudate that extended into the adjacent intercotyledonary areas. Histologically, there was severe suppurative and necrotizing placentitis with vasculitis (arteriolitis) and thrombosis, multifocal lymphohistiocytic and neutrophilic hepatitis (A), and fibrinosuppurative enteritis in both fetuses. Chlamydia antigen was detected in the placenta by the direct fluorescent antibody test and in fetal intestines by immunohistochemistry. Nested polymerase chain reaction of DNA extracted from formalin-fixed, paraffin-embedded sections of placenta and intestine amplified 400 bp of the Chlamydia 16S rRNA gene that was sequenced and found to be 99% identical to C. pecorum by BLAST analysis. Other known abortigenic infectious agents were ruled out by specific testing. It is concluded that C. pecorum infection is associated with fetoplacental lesions and sporadic abortion in goats.

  19. A unified genetic theory for sporadic and inherited autism

    PubMed Central

    Zhao, Xiaoyue; Leotta, Anthony; Kustanovich, Vlad; Lajonchere, Clara; Geschwind, Daniel H.; Law, Kiely; Law, Paul; Qiu, Shanping; Lord, Catherine; Sebat, Jonathan; Ye, Kenny; Wigler, Michael

    2007-01-01

    Autism is among the most clearly genetically determined of all cognitive-developmental disorders, with males affected more often than females. We have analyzed autism risk in multiplex families from the Autism Genetic Resource Exchange (AGRE) and find strong evidence for dominant transmission to male offspring. By incorporating generally accepted rates of autism and sibling recurrence, we find good fit for a simple genetic model in which most families fall into two types: a small minority for whom the risk of autism in male offspring is near 50%, and the vast majority for whom male offspring have a low risk. We propose an explanation that links these two types of families: sporadic autism in the low-risk families is mainly caused by spontaneous mutation with high penetrance in males and relatively poor penetrance in females; and high-risk families are from those offspring, most often females, who carry a new causative mutation but are unaffected and in turn transmit the mutation in dominant fashion to their offspring. PMID:17652511

  20. Analysis of GLRA 1 in familial and sporadic hyperekplexia

    SciTech Connect

    Elmslie, F.V.; Rees, M.; Covanis, A.

    1994-09-01

    Hyperekplexia or familial startle syndrome is an autosomal dominant condition, causing an exaggerated startle response to unexpected stimuli. Infants have variable hypertonia in the neonatal period, with a startle response causing sustained muscular contraction. The gene was localized to chromosome 5q in 1992 and subsequently mutations were detected in the alpha{sub 1} subunit of the glycine receptor in four large pedigrees with hyperekplexia. Eight probands with hyperekplexia have been ascertained, including three sporadic and four familial cases. In one pedigree, hyperekplexia appears to be associated with spastic paraparesis, and the hyperekplexia/spastic paraparesis is linked to marker loci on chromosome 5q. Genomic DNA was extracted from white cells. GLRA1 exons were amplified from genomic DNA by PCR using specific oligonucleotide primers. Amplified exon 6 fragments are being screened for the previously described mutations by restriction enzyme analysis using Bfa1 and Xho1. In addition, all exons have been screened by single-stranded conformational polymorphism (SSCP) and are currently being screened by heteroduplex analysis. No sequence changes have been detected to date. Products displaying aberrant bands on screening will be analyzed further by di-deoxy sequencing.

  1. Facing and managing natural disasters in the Sporades Islands, Greece

    NASA Astrophysics Data System (ADS)

    Karanikola, P.; Panagopoulos, T.; Tampakis, S.; Karantoni, M. I.; Tsantopoulos, G.

    2013-11-01

    The region of the Sporades Islands located in central Greece is at the mercy of many natural phenomena, such as earthquakes, due to the marine volcano "Psathoura", and the rift of Anatolia, forest fires, floods, landslides, storms, hail, snowfall and frost. The present work aims at studying the perceptions and attitudes of the residents regarding how they face and manage natural disasters. A positive public response during a hazard crisis depends not only upon the availability and good management of a civil defence plan but also on the knowledge and perception of the possible hazards by the local population. It is important for the stakeholders to know what the citizens expect from each of the separate stakeholders so that the necessary structures can be developed in the phase of preparation and organization. The residents were asked about their opinion about what they think should be done by the stakeholders after a catastrophic natural disaster, particularly the immediate response of stakeholders and their involvement and responsibilities at different, subsequent intervals of time following the disaster. The residents were also asked about the most common disasters that happen in their region and about the preparation activities of the stakeholders.

  2. Facing and managing natural disasters in the Sporades islands, Greece

    NASA Astrophysics Data System (ADS)

    Karanikola, P.; Panagopoulos, T.; Tampakis, S.; Karantoni, M. I.; Tsantopoulos, G.

    2014-04-01

    The region of the Sporades islands located in central Greece is at the mercy of many natural phenomena, such as earthquakes due to the marine volcano Psathoura and the rift of Anatolia, forest fires, floods, landslides, storms, hail, snowfall and frost. The present work aims at studying the perceptions and attitudes of the residents regarding how they face and manage natural disasters. A positive public response during a hazard crisis depends not only upon the availability and good management of a civil defense plan but also on the knowledge and perception of the possible hazards by the local population. It is important for the stakeholders to know what the citizens expect so that the necessary structures can be developed in the phase of preparation and organization. The residents were asked their opinion about what they think should be done by the stakeholders after a catastrophic natural disaster, particularly about the immediate response of stakeholders and their involvement and responsibilities at different, subsequent intervals of time following the disaster. The residents were also asked about the most common disasters that happen in their region and about the preparation activities of the stakeholders.

  3. CAMS newly detected meteor showers and the sporadic background

    NASA Astrophysics Data System (ADS)

    Jenniskens, P.; Nénon, Q.; Gural, P. S.; Albers, J.; Haberman, B.; Johnson, B.; Morales, R.; Grigsby, B. J.; Samuels, D.; Johannink, C.

    2016-03-01

    The Cameras for Allsky Meteor Surveillance (CAMS) video-based meteoroid orbit survey adds 60 newly identified showers to the IAU Working List of Meteor Showers (numbers 427, 445-446, 506-507, and part of 643-750). 28 of these are also detected in the independent SonotaCo survey. In total, 230 meteor showers and shower components are identified in CAMS data, 177 of which are detected in at least two independent surveys. From the power-law size frequency distribution of detected showers, we extrapolate that 36% of all CAMS-observed meteors originated from ∼700 showers above the N = 1 per 110,000 shower limit. 71% of mass falling to Earth from streams arrives on Jupiter-family type orbits. The transient Geminids account for another 15%. All meteoroids not assigned to streams form a sporadic background with highest detected numbers from the apex source, but with 98% of mass falling in from the antihelion source. Even at large ∼7-mm sizes, a Poynting-Robertson drag evolved population is detected, which implies that the Grün et al. collisional lifetimes at these sizes are underestimated by about a factor of 10. While these large grains survive collisions, many fade on a 104-y timescale, possibly because they disintegrate into smaller particles by processes other than collisions, leaving a more resilient population to evolve.

  4. 20 March 2015 solar eclipse influence on sporadic E layer

    NASA Astrophysics Data System (ADS)

    Pezzopane, M.; Pietrella, M.; Pignalberi, A.; Tozzi, R.

    2015-11-01

    This paper shows how the solar eclipse occurred on 20 March 2015 influenced the sporadic E (Es) layer as recorded by the Advanced Ionospheric Sounder by Istituto Nazionale di Geofisica e Vulcanologia (AIS-INGV) ionosondes installed at Rome (41.8°N, 12.5°E) and Gibilmanna (37.9°N, 14.0°E), Italy. In these locations, the solar eclipse was only partial, with the maximum area of the solar disk obscured by the Moon equal to ∼54% at Rome and ∼45% at Gibilmanna. Nevertheless, it is shown that the strong thermal gradients that usually accompany a solar eclipse, have significantly influenced the Es phenomenology. Specifically, the solar eclipse did not affect the Es layer in terms of its maximum intensity, which is comparable with that of the previous and next day, but rather in terms of its persistence. In fact, both at Rome and Gibilmanna, contrary to what typically happens in March, the Es layer around the solar eclipse time is always present. On the other hand, this persistence is also confirmed by the application of the height-time-intensity (HTI) technique. A detailed analysis of isoheight ionogram plots suggests that traveling ionospheric disturbances (TIDs) likely caused by gravity wave (GW) propagation have played a significant role in causing the persistence of the Es layer.

  5. Targeting Protein Homeostasis in Sporadic Inclusion Body Myositis

    PubMed Central

    Ahmed, Mhoriam; Machado, Pedro M.; Miller, Adrian; Spicer, Charlotte; Herbelin, Laura; He, Jianghua; Noel, Janelle; Wang, Yunxia; McVey, April L.; Pasnoor, Mamatha; Gallagher, Philip; Statland, Jeffrey; Lu, Ching-Hua; Kalmar, Bernadett; Brady, Stefen; Sethi, Huma; Samandouras, George; Parton, Matt; Holton, Janice L.; Weston, Anne; Collinson, Lucy; Taylor, J. Paul; Schiavo, Giampietro; Hanna, Michael G.; Barohn, Richard J.; Dimachkie, Mazen M.; Greensmith, Linda

    2016-01-01

    Sporadic inclusion body myositis (sIBM) is the commonest severe myopathy in patients over age 50. Previous therapeutic trials have targeted the inflammatory features of sIBM, but all have failed. Since protein dyshomeostasis may also play a role in sIBM, we tested the effects of targeting this feature of the disease. Using rat myoblast cultures, we found that up-regulation of the heat shock response with Arimoclomol reduced key pathological markers of sIBM in vitro. Furthermore, in mutant valosin-containing protein VCP mice, which develop an inclusion body myopathy (IBM), treatment with Arimoclomol ameliorated disease pathology and improved muscle function. We therefore evaluated the safety and tolerability of Arimoclomol in an investigator-lead, randomised, double-blind, placebo-controlled, proof-of-concept patient trial and gathered exploratory efficacy data which showed that Arimoclomol was safe and well tolerated. Although Arimoclomol improved some IBM-like pathology in vitro and in vivo in the mutant VCP mouse, we did not see statistically significant evidence of efficacy in this proof of concept patient trial. PMID:27009270

  6. Mid-latitude lidar observations of large sporadic sodium layers

    SciTech Connect

    Senft, D.C.; Collins, R.L.; Gardner, C.S. )

    1989-07-01

    During the early morning of October 31, 1988 two large sporadic Na (Na{sub s}) layers were observed near the mesopause above Urbana, IL (40{degree}N, 88{degree}W) with a Na lidar system. The layers began forming near 102 km at 0026 LST and 0110 LST and moved downward with vertical velocities as high as 4 ms{sup {minus}1} before dissipating between 94 and 96 km. The duration of each layer was approximately 80 min. The layers were narrow ({approximately} 1 km FWHM) and dense with maximum densities approaching 7,800 cm{sup {minus}3}. The characteristics of these two Na{sub s} layers are very similar to those of similar phenomena observed recently at Andoya, Norway and Mauna Kea, Hawaii. Lidar observations of the mesospheric Na layer have been conducted routinely by several groups at mid-latitudes for almost 20 years. Although large Na{sub s} layers now appear to be relatively common at low- and high-latitudes, to our knowledge the two layers described in this letter are only the second observation of this puzzling phenomenon at mid-latitudes.

  7. EFEMP1 is not associated with sporadic early onset drusen.

    PubMed

    Sauer, C G; White, K; Kellner, U; Rudolph, G; Jurklies, B; Pauleikhoff, D; Weber, B H

    2001-03-01

    The early onset of multiple drusen in the posterior pole of the retina is characteristic of a group of macular dystrophies often referred to as dominant or radial drusen. At least two forms, Doyne honeycomb retinal dystrophy (DHRD) and Malattia Leventinese (MLVT), are associated with a single missense mutation (R345W) in the gene encoding the EGF-containing fibulin-like extracellular matrix protein-1 (EFEMP1) and are now thought to represent a single entity. Here, we present a further evaluation of the role of EFEMP1 in the pathogenesis of sporadic forms of early onset drusen. We analyzed all coding exons of the EFEMP1 gene by SSCP analysis in 14 unrelated individuals with early onset of multiple drusen and no apparent family history of the disease. In this patient group, we did not detect the R345W mutation or any other disease-associated mutation. Three different polymorphisms and two intragenic polymorphic repeats were present in similar frequencies in the patients and control individuals. We conclude that EFEMP1 is unlikely to be involved in the disease in this patient group. This suggests that mutations in a different as yet unknown gene or genes may lead to the early onset drusen phenotype.

  8. Vitamin D receptor gene polymorphisms, smoking, and risk of sporadic Parkinson's disease in Japan.

    PubMed

    Tanaka, Keiko; Miyake, Yoshihiro; Fukushima, Wakaba; Kiyohara, Chikako; Sasaki, Satoshi; Tsuboi, Yoshio; Oeda, Tomoko; Shimada, Hiroyuki; Kawamura, Nobutoshi; Sakae, Nobutaka; Fukuyama, Hidenao; Hirota, Yoshio; Nagai, Masaki; Nakamura, Yoshikazu

    2017-03-16

    Epidemiological evidence on the relationships between the vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI), and rs2228570 (FokI) and Parkinson's disease (PD) is inconsistent. We investigated these relationships in 229 sporadic PD patients within six years of onset in Japan. Controls were 357 patients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, and smoking. A significant inverse association was found between SNP rs2228570 and the risk of sporadic PD under the additive but not the co-dominant or dominant model (P=0.048); however, this fell below significance after adjustment for multiple comparisons (adjusted P=0.46). No significant relationships were found between SNPs rs731236, rs7975232, or rs1544410 and the risk of sporadic PD in any genetic model. VDR haplotypes inferred in the current study were not associated with sporadic PD. Compared with subjects with the GA or AA genotype of SNP rs2228570 who had ever smoked, those with the GG genotype who had never smoked had a 3.78-fold increased risk of sporadic PD; however, no significant interaction was observed. VDR SNP rs2228570 may be associated with sporadic PD in Japan. Smoking did not significantly modify the relationship between SNP rs2228570 and sporadic PD.

  9. Minor physical anomalies in familial and sporadic schizophrenia: the Maudsley family study

    PubMed Central

    Griffiths, T; Sigmundsson, T; Takei, N; Frangou, S; Birkett, P; Sharma, T; Reveley, A; Murray, R

    1998-01-01

    OBJECTIVES—(1) To test the hypothesis that minor physical anomalies are increased in patients with schizophrenia and (2) to investigate differences in the prevalence of minor physical anomalies in patients with familial and sporadic schizophrenia and their first degree relatives.
METHODS—A weighted Waldrop assessment was carried out on 214 subjects in five groups: schizophrenic patients from multiply affected families; first degree relatives of these familial schizophrenic patients; sporadic schizophrenic patients; first degree relatives of these sporadic schizophrenic patients, and normal controls. Broad and narrow criteria for abnormality were defined based on the distribution of minor physical anomalies in the control group.
RESULTS—(1) The total schizophrenic group did not have a significant increase in minor physical anomalies using a narrow criterion of abnormality, but did when a broader criterion was used. (2) A significant increase in the proportion of subjects with an abnormally high number of minor physical abnormalities was shown in the group of sporadic schizophrenic patients (uncorrected p<0.01). Separate analyses for males and females showed a significant increase in the male sporadic group (uncorrected p<0.05), and a smaller non-significant increase in the female sporadic group. Neither the familial schizophrenic group nor either group of first degree relatives showed any significant increases in the proportion of patients with high abnormality scores.
CONCLUSION—This work supports prenatal developmental abnormality as a mechanism for sporadic, but not familial, schizophrenia.

 PMID:9436728

  10. Coincident extremely large sporadic sodium and sporadic E layers observed in the lower thermosphere over Colorado and Utah

    NASA Astrophysics Data System (ADS)

    Williams, B. P.; Berkey, F. T.; Sherman, J.; She, C. Y.

    2007-02-01

    On the night of 2 June 2002, the sodium lidar in Fort Collins, CO (40.6 N, 105 W) measured an extremely strong sporadic sodium layer lasting from 03:30 to 05:00 UT with several weaker layers later in the night at 06:00 and 09:00 UT. There is a double layer structure with peaks at 101 and 104 km. The peak sodium density was 21 000 atoms/cm3 with a column abundance of up to twice that of the normal sodium layer. The peak density was 500 times greater than the typical density at that altitude. The sporadic layer abundance and strength factor were higher than any reported in the literature. The two lidar beams, separated by 70 km at this altitude, both measured 0.6 h periodicities in the abundance, but out of phase with each other by 0.3 h. There is also evidence for strong wave activity in the lidar temperatures and winds. The NOAA ionosonde in Boulder, CO (40.0 N, 105 W) measured a critical frequency (foEs) of 14.3 MHz at 03:00 UT on this night, the highest value anytime during 2002. The high values of total ion density inferred means that Na+ fraction must have been only a few percent to explain the neutral Na layer abundances. The Bear Lake, Utah (41.9 N, 111.4 W) dynasonde also measured intense Es between 02:00 and 05:00 UT and again from 06:00 to 08:00 UT about 700 km west of the lidar, with most of the ionograms during these intervals measuring Es up to 12 MHz, the limit of the ionosonde sweep. Other ionosondes around North America on the NGDC database measured normal foEs values that night, so it was a localized event within North America. The peak of Es activity observed in Europe during the summer of 2002 occurred on 4 June. The observations are consistent with the current theories where a combination of wind shears and long period waves form and push downward a concentrated layer of ions, which then chemically react and form a narrow layer of sodium atoms.

  11. Daytime Observations of Mid-latitude Sporadic-E and QP Radar Echoes

    NASA Astrophysics Data System (ADS)

    Pfaff, R. F.; Liebrecht, C.; Urbina, J.; Kudeki, E.

    2007-12-01

    Although sporadic-E layers and quasi-periodic (QP) radars are typically detected during nighttime conditions at mid-latitudes, they also may exist in the daytime lower ionosphere as well. We present observations of ionosonde observations of daytime sporadic-E layers gathered at the Wallops Flight Facility, Virginia, in the late morning to noon local times. The data reveal sporadic-E characteristics similar to nighttime observations including considerable variations in frequency and altitude. For one event, observed on 23 July 1999 near 14 U.T. (10 L.T.), we present coincident strong Wallops ionosonde sporadic-E observations and 50MHz backscatter radar observations of quasi-periodic echoes gathered with the University of Illinois radar situated at Ft. Macon, N.C., whose beam was perpendicular to the magnetic field in the lower E-region over Wallops. The radar data show daytime QP structuring that is very similar to the nighttime observations, suggesting a similar driving mechanism. A statistical survey of the daytime ionogram data at Wallops shows a preponderance of daytime sporadic-E events occurring during the local summer months, a seasonal dependence that is well-established for nighttime sporadic-E conditions in the northern hemisphere. No clear correlation is observed between the daytime sporadic-E events and magnetic storms, suggesting that the daytime sporadic-E events are not necessarily driven by the disturbance dynamo. Rather, we speculate that the same large wind shears that are believed to be the main engine for the nighttime sporadic-E and QP echoes, may also be at work during the daytime. The existence of enhanced plasma density layers during the daytime and their role in generating QP- echoes during the day remain open questions.

  12. From similitude to success: The effects of facial resemblance on perceptions of team effectiveness.

    PubMed

    Wang, Ze; He, Xin; Liu, Fan

    2016-03-01

    Scant empirical research has focused on how impressions of teams are formed based on members' collective appearance, even though team photos are omnipresent in visual communications and teamwork is a common theme to elicit positive responses. Across 4 studies, we show that a subtle increase in the facial resemblance among team members enhances observers' evaluations of team effectiveness. This resemblance effect is mediated by perceived cooperative intent among team players. Furthermore, we demonstrate a reversal of the resemblance effect through the moderating role of information valence and extend the finding from team perception to behavioral intention. These results hold across different manipulations, contexts, stimuli, and sample characteristics. Collectively, this research presents the first empirical evidence that inferences based on facial morphology persist well beyond evaluations of individuals to influence the way a team, as a whole, is perceived.

  13. Identification of Epigenetically Altered Genes in Sporadic Amyotrophic Lateral Sclerosis

    PubMed Central

    Bender, Diane E.; Delaney, Colin E.; Cataldo, Michael D.; Smith, Andrea L.; Yung, Raymond; Ruden, Douglas M.; Callaghan, Brian C.; Feldman, Eva L.

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a terminal disease involving the progressive degeneration of motor neurons within the motor cortex, brainstem and spinal cord. Most cases are sporadic (sALS) with unknown causes suggesting that the etiology of sALS may not be limited to the genotype of patients, but may be influenced by exposure to environmental factors. Alterations in epigenetic modifications are likely to play a role in disease onset and progression in ALS, as aberrant epigenetic patterns may be acquired throughout life. The aim of this study was to identify epigenetic marks associated with sALS. We hypothesize that epigenetic modifications may alter the expression of pathogenesis-related genes leading to the onset and progression of sALS. Using ELISA assays, we observed alterations in global methylation (5 mC) and hydroxymethylation (5 HmC) in postmortem sALS spinal cord but not in whole blood. Loci-specific differentially methylated and expressed genes in sALS spinal cord were identified by genome-wide 5mC and expression profiling using high-throughput microarrays. Concordant direction, hyper- or hypo-5mC with parallel changes in gene expression (under- or over-expression), was observed in 112 genes highly associated with biological functions related to immune and inflammation response. Furthermore, literature-based analysis identified potential associations among the epigenes. Integration of methylomics and transcriptomics data successfully revealed methylation changes in sALS spinal cord. This study represents an initial identification of epigenetic regulatory mechanisms in sALS which may improve our understanding of sALS pathogenesis for the identification of biomarkers and new therapeutic targets. PMID:23300739

  14. Endoscopic treatment of sporadic small duodenal and ampullary neuroendocrine tumors.

    PubMed

    Gincul, Rodica; Ponchon, Thierry; Napoleon, Bertrand; Scoazec, Jean-Yves; Guillaud, Olivier; Saurin, Jean-Christophe; Ciocirlan, Mihai; Lepilliez, Vincent; Pioche, Mathieu; Lefort, Christine; Adham, Mustapha; Pialat, Jean; Chayvialle, Jean-Alain; Walter, Thomas

    2016-11-01

    Background and study aim: As duodenal neuroendocrine tumors (NETs) are rare, their optimal management has not been clearly established. The aim of this study was to evaluate the feasibility and outcome of endoscopic treatment of duodenal NETs. Patients and methods: We reviewed the files of all patients who underwent endoscopic resection of a sporadic duodenal or ampullary NET between 1996 and 2014 at two centers. Results: A total of 29 patients with 32 uT1N0M0 NETs < 20 mm were included. Treatment consisted of endoscopic mucosal resection in 19 cases, and cap aspiration in 13 cases. Prior submucosal saline injection was used in 15 cases. Mortality was 3 % (one severe bleeding). Morbidity was 38 % (11/29). At post-resection analysis, mean tumor size was 8.9 mm (range 3 - 17 mm), 29 lesions were stage pT1, one was pT2, and 2 were pTx because of piecemeal resection. All NETs were well differentiated. A total of 27 lesions were classified as grade 1 and 5 were grade 2. The resection was R0, R1, and Rx for 16, 14, and 2 lesions, respectively. Three R1 patients underwent additional surgical treatment, with no residual tumor on the surgical specimen but with positive metastatic lymph nodes in two cases. One patient was lost to follow-up. Finally, 24 patients were included in the follow-up analysis. The median follow-up period was 56 months (range 6 - 175 months). Two patients presented a tumor recurrence during the follow-up period. Conclusions: Endoscopic treatment of small duodenal NETs was associated with significant morbidity, a difficulty in obtaining an R0 specimen, and the risk of lymph node metastasis. Nevertheless, it represents an interesting alternative in small grade 1 duodenal lesions and in patients at high surgical risk.

  15. Multiple sporadic colorectal cancers display a unique methylation phenotype.

    PubMed

    Gonzalo, Victoria; Lozano, Juan Jose; Alonso-Espinaco, Virginia; Moreira, Leticia; Muñoz, Jenifer; Pellisé, Maria; Castellví-Bel, Sergi; Bessa, Xavier; Andreu, Montserrat; Xicola, Rosa M; Llor, Xavier; Ruiz-Ponte, Clara; Carracedo, Angel; Jover, Rodrigo; Castells, Antoni; Balaguer, Francesc

    2014-01-01

    Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC). Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP); KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1). Methylight assays validated the results for 4 selected genes (p = 0.0002). Eight out of 12(66.6%) multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2%) solitary tumors (p = 0.004). Interestingly, 76 out of the 102 (74.5%) hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity.

  16. Clinical Perspective of Oxidative Stress in Sporadic ALS

    PubMed Central

    D’Amico, Emanuele; Factor-Litvak, Pam; Santella, Regina M.; Mitsumoto, Hiroshi

    2013-01-01

    Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis. PMID:23797033

  17. Quinacrine treatment trial for sporadic Creutzfeldt-Jakob disease

    PubMed Central

    Kuo, Amy L.; Wong, Katherine S.; Haman, Aissa; Devereux, Gillian; Raudabaugh, Benjamin J.; Johnson, David Y.; Torres-Chae, Charles C.; Finley, Ron; Garcia, Paul; Thai, Julie N.; Cheng, Hugo Q.; Neuhaus, John M.; Forner, Sven A.; Duncan, Jacque L.; Possin, Katherine L.; DeArmond, Stephen J.; Prusiner, Stanley B.; Miller, Bruce L.

    2013-01-01

    Objective: To determine whether oral quinacrine increases survival in sporadic Creutzfeldt-Jakob disease (sCJD). Methods: This NIH/National Institute on Aging–funded, double-blinded, placebo-controlled, stratified randomization treatment trial was conducted at the University of California, San Francisco from February 2005 through May 2009 (ClinicalTrials.gov, NCT00183092). Subjects were randomized (50:50) to quinacrine (300 mg daily) or placebo with inpatient evaluations at baseline, and planned for months 2, 6, and 12. Subjects returning for their month-2 visit were offered open-label quinacrine. The primary outcome was survival from randomization to month 2. Results: Of 425 patients referred, 69 subjects enrolled, 54 subjects were randomized to active drug or placebo, and 51 subjects with sCJD were included in survival analyses. Survival for the randomized portion of the trial (first 2 months) showed no significant difference between the 2 groups (log-rank statistic, p = 0.43; Cox proportional relative hazard = 1.43, quinacrine compared with placebo, 95% confidence interval = 0.58, 3.53). The quinacrine-treated group, however, declined less on 2 of 3 functional scales, the modified Rankin and Clinical Dementia Rating, than the placebo group during the first 2 months. Conclusion: This interventional study provides Class I evidence that oral quinacrine at 300 mg per day does not improve 2-month survival of patients with sCJD, compared with placebo. Importantly, this study shows that double-blinded, placebo-controlled, randomized treatment trials are possible in prion disease. Furthermore, the quantitative data collected on the course of sCJD will be useful for future trials. Classification of evidence: This study provides Class I evidence that quinacrine does not improve survival for people with sCJD when given orally at a dose of 300 mg per day for 2 months. PMID:24122181

  18. Multiple Sporadic Colorectal Cancers Display a Unique Methylation Phenotype

    PubMed Central

    Gonzalo, Victoria; Lozano, Juan Jose; Alonso-Espinaco, Virginia; Moreira, Leticia; Muñoz, Jenifer; Pellisé, Maria; Castellví-Bel, Sergi; Bessa, Xavier; Andreu, Montserrat; Xicola, Rosa M.; Llor, Xavier; Ruiz-Ponte, Clara; Carracedo, Angel; Jover, Rodrigo; Castells, Antoni; Balaguer, Francesc

    2014-01-01

    Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC). Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP); KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1). Methylight assays validated the results for 4 selected genes (p = 0.0002). Eight out of 12(66.6%) multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2%) solitary tumors (p = 0.004). Interestingly, 76 out of the 102 (74.5%) hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity. PMID:24643221

  19. Visual art therapy in sporadic Creutzfeldt-Jakob disease: a case study.

    PubMed

    Shrestha, Rajeet; Trauger-Querry, Barbara; Loughrin, Athena; Appleby, Brian S

    2016-01-01

    This paper describes the diagnostic and treatment utility of visual art therapy in a case of sporadic Creutzfeldt-Jakob disease. Visual art therapy was compared longitudinally with clinical and neuroimaging data over five-month period in an autopsy-confirmed case of sporadic Creutzfeldt-Jakob disease of MM2-cortical subtype. Art therapy sessions and content were useful in ascertaining neuropsychiatric symptoms during the course of her illness. Art therapy offered a unique emotional and cognitive outlet as illness progressed. Patients and families affected by sporadic Creutzfeldt-Jakob disease may benefit from art therapy despite the rapidly progressive nature of the illness. Art therapy can also be useful for assessment of patients with sporadic Creutzfeldt-Jakob disease by healthcare professionals.

  20. Molecular interactions between prions as seeds and recombinant prion proteins as substrates resemble the biological interspecies barrier in vitro.

    PubMed

    Panza, Giannantonio; Luers, Lars; Stöhr, Jan; Nagel-Steger, Luitgard; Weiss, Jürgen; Riesner, Detlev; Willbold, Dieter; Birkmann, Eva

    2010-12-09

    Prion diseases like Creutzfeldt-Jakob disease in humans, Scrapie in sheep or bovine spongiform encephalopathy are fatal neurodegenerative diseases, which can be of sporadic, genetic, or infectious origin. Prion diseases are transmissible between different species, however, with a variable species barrier. The key event of prion amplification is the conversion of the cellular isoform of the prion protein (PrP(C)) into the pathogenic isoform (PrP(Sc)). We developed a sodiumdodecylsulfate-based PrP conversion system that induces amyloid fibril formation from soluble α-helical structured recombinant PrP (recPrP). This approach was extended applying pre-purified PrP(Sc) as seeds which accelerate fibrillization of recPrP. In the present study we investigated the interspecies coherence of prion disease. Therefore we used PrP(Sc) from different species like Syrian hamster, cattle, mouse and sheep and seeded fibrillization of recPrP from the same or other species to mimic in vitro the natural species barrier. We could show that the in vitro system of seeded fibrillization is in accordance with what is known from the naturally occurring species barriers.

  1. Children and Adolescents' Understandings of Family Resemblance: A Study of Naive Inheritance Concepts

    ERIC Educational Resources Information Center

    Williams, Joanne M.

    2012-01-01

    This paper aims to provide developmental data on two connected naive inheritance concepts and to explore the coherence of children's naive biology knowledge. Two tasks examined children and adolescents' (4, 7, 10, and 14 years) conceptions of phenotypic resemblance across kin (in physical characteristics, disabilities, and personality traits). The…

  2. Schwannoma of the biliary tract resembling cholangiocarcinoma: A case report and review

    PubMed Central

    Garcia Sanz, I; Muñoz de Nova, JL; Valdés de Anca, A; Martín Pérez, ME

    2016-01-01

    Schwannomas are benign tumours derived from Schwann cells and are extremely rare in the biliary tract. We present the case of a 62-year-old patient with a common bile duct schwannoma that resembled a cholangiocarcinoma. We also review all 17 previously published cases of schwannoma of the biliary tract and discuss the challenges of preoperative diagnosis. PMID:27269434

  3. LINGAM AS A SACRED OBJECT AND THE HEAD-DRESS OF SUFI RESEMBLING IT

    PubMed Central

    Mahdihassan, S.

    1990-01-01

    This study scans into past of ancient man and discusses meticulously how the reproductive organ Lingam became sacred object to Hindus and why a sufi wore a phallus shaped head-dress resembling to it. In this manner the author demystifies here the procreation, the law of nature. PMID:22557692

  4. Familial Adenomatous Polyposis-Associated Desmoids Display Significantly More Genetic Changes than Sporadic Desmoids

    PubMed Central

    Robanus-Maandag, Els; Bosch, Cathy; Amini-Nik, Saeid; Knijnenburg, Jeroen; Szuhai, Karoly; Cervera, Pascale; Poon, Raymond; Eccles, Diana; Radice, Paolo; Giovannini, Marco; Alman, Benjamin A.; Tejpar, Sabine; Devilee, Peter; Fodde, Riccardo

    2011-01-01

    Desmoid tumours (also called deep or aggressive fibromatoses) are potentially life-threatening fibromatous lesions. Hereditary desmoid tumours arise in individuals affected by either familial adenomatous polyposis (FAP) or hereditary desmoid disease (HDD) carrying germline mutations in APC. Most sporadic desmoids carry somatic mutations in CTNNB1. Previous studies identified losses on 5q and 6q, and gains on 8q and 20q as recurrent genetic changes in desmoids. However, virtually all genetic changes were derived from sporadic tumours. To investigate the somatic alterations in FAP-associated desmoids and to compare them with changes occurring in sporadic tumours, we analysed 17 FAP-associated and 38 sporadic desmoids by array comparative genomic hybridisation and multiple ligation-dependent probe amplification. Overall, the desmoids displayed only a limited number of genetic changes, occurring in 44% of cases. Recurrent gains at 8q (7%) and 20q (5%) were almost exclusively found in sporadic tumours. Recurrent losses were observed for a 700 kb region at 5q22.2, comprising the APC gene (11%), a 2 Mb region at 6p21.2-p21.1 (15%), and a relatively large region at 6q15-q23.3 (20%). The FAP-associated desmoids displayed a significantly higher frequency of copy number abnormalities (59%) than the sporadic tumours (37%). As predicted by the APC germline mutations among these patients, a high percentage (29%) of FAP-associated desmoids showed loss of the APC region at 5q22.2, which was infrequently (3%) seen among sporadic tumours. Our data suggest that loss of region 6q15-q16.2 is an important event in FAP-associated as well as sporadic desmoids, most likely of relevance for desmoid tumour progression. PMID:21931686

  5. [Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

    PubMed

    Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

    2017-01-25

    Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls (t=-3.536, P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group (r=0.494, P<0.01), and the same correlation as CEA and CA(199) group (r=0.897, P<0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group (P>0

  6. Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers

    PubMed Central

    Detours, V; Delys, L; Libert, F; Weiss Solís, D; Bogdanova, T; Dumont, J E; Franc, B; Thomas, G; Maenhaut, C

    2007-01-01

    Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profiles of PTCs from the Chernobyl Tissue Bank (CTB, n=12) and from French patients with no history of exposure to ionising radiations (n=14). We also compared the transcriptional responses of human lymphocytes to the presumed aetiological agents initiating these tumours, γ-radiation and H2O2. On a global scale, the transcriptomes of CTB and French tumours are indistinguishable, and the transcriptional responses to γ-radiation and H2O2 are similar. On a finer scale, a 118 genes signature discriminated the γ-radiation and H2O2 responses. This signature could be used to classify the tumours as CTB or French with an error of 15–27%. Similar results were obtained with an independent signature of 13 genes involved in homologous recombination. Although sporadic and radio-induced PTCs represent the same disease, they are distinguishable with molecular signatures reflecting specific responses to γ-radiation and H2O2. These signatures in PTCs could reflect the susceptibility profiles of the patients, suggesting the feasibility of a radiation susceptibility test. PMID:17712314

  7. HEREDITARY, SPORADIC AND METASTATIC COLORECTAL CANCER ARE COMMONLY DRIVEN BY SPECIFIC SPECTRUMS OF DEFECTIVE DNA MISMATCH REPAIR COMPONENTS

    PubMed Central

    CARETHERS, JOHN M.

    2016-01-01

    DNA mismatch repair (MMR) is one of several human cell mechanisms utilized to repair mutable mistakes within DNA, particularly after DNA is replicated. MMR function is dependent upon heterodimerization of specific MMR proteins that can recognize base-base mispairs as well as frameshifts at microsatellite sequences, followed by the triggering of other complementary proteins that execute excision and repair or initiate cell demise if repair is futile. MMR function is compromised in specific disease states, all of which can be biochemically recognized by faulty repair of microsatellite sequences, causing microsatellite instability. Germline mutation of an MMR gene causes Lynch syndrome, the most common inherited form of colorectal cancer (CRC), and biallelic germline mutations cause the rare constitutional mismatch repair deficiency syndrome. Somatic inactivation of MMR through epigenetic mechanisms is observed in 15% of sporadic CRC, and a smaller portion of CRCs possess biallelic somatic mutations. A novel inflammation-driven nuclear-to-cytoplasmic shift of the specific MMR protein hMSH3 is seen in up to 60% of sporadic CRCs that associates with metastasis and poor patient prognosis, unlike improved outcome when MMR is genetically inactivated. The mechanism for MMR inactication as well as the component affected dictates the clinical spectrum and clinical response for patients. PMID:28066040

  8. Subtype and Regional-Specific Neuroinflammation in Sporadic Creutzfeldt–Jakob Disease

    PubMed Central

    Llorens, Franc; López-González, Irene; Thüne, Katrin; Carmona, Margarita; Zafar, Saima; Andréoletti, Olivier; Zerr, Inga; Ferrer, Isidre

    2014-01-01

    The present study identifies deregulated cytokines and mediators of the immune response in the frontal cortex and cerebellum of sporadic Creutzfeldt–Jakob disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls. Deregulated genes include pro- and anti-inflammatory cytokines, toll-like receptors, colony stimulating factors, cathepsins, members of the complement system, and members of the integrin and CTL/CTLD family with particular regional and sCJD subtype patterns. Analysis of cytokines and mediators at protein level shows expression of selected molecules and receptors in neurons, in astrocytes, and/or in microglia, thus suggesting interactions between neurons and glial cells, mainly microglia, in the neuroinflammatory response in sCJD. Similar inflammatory responses have been shown in the tg340 sCJD MM1 mice, revealing a progressive deregulation of inflammatory mediators with disease progression. Yet, inflammatory molecules involved are subjected to species differences in humans and mice. Moreover, inflammatory-related cell signaling pathways NFκB/IKK and JAK/STAT are activated in sCJD and sCJD MM1 mice. Together, the present observations show a self-sustained complex inflammatory and inflammatory-related responses occurring already at early clinical stages in animal model and dramatically progressing at advanced stages of sCJD. Considering this scenario, measures tailored to modulate (activate or inhibit) specific molecules could be therapeutic options in CJD. PMID:25136317

  9. The TP53 Codon 72 Polymorphism and Risk of Sporadic Prostate Cancer among Iranian Patients

    PubMed Central

    BABAEI, Farhad; AHMADI, Seyed Ali; ABIRI, Ramin; REZAEI, Farhad; NASERI, Maryam; MAHMOUDI, Mahmoud; NATEGH, Rakhshande; MOKHTARI AZAD, Talat

    2014-01-01

    Abstract Background The TP53 gene is one of the most frequently mutated genes amongst human malignancies, particularly TP53 codon 72 polymorphism. Furthermore, an association between the TP53 codon 72 variants and prostate cancer has been reported in several studies. Although some studies have indicated an association between the TP53 Arg/Arg variant and an increased risk for prostate cancer, other studies have shown a positive correlation between the TP53 Pro/Pro genotype instead. Therefore, to clarify if this polymorphism is associated with an increased risk of prostate cancer in Iranian men, we conducted a case-control study of 40 sporadic prostate cancer patients and 80 benign prostate hyperplasia cases. Methods The TP53 codon 72 was genotyped using an allele specific PCR. Results A significant association between the TP53 codon 72 genotype and prostate cancer risk was found (OR = 6.8, 95% CI = [1.8-25.1], P = 0.005). However, the results of this study did not support an association between age, the Gleason score nor TP53 genotype at codon 72 in prostate cancer patients. Conclusions TP53 codon 72 polymorphism may have a great impact in the development of prostate cancer. PMID:26005655

  10. Sporadic Hirschsprung`s disease due to a novel nonsense mutation in the RET protooncogene

    SciTech Connect

    Carlson, K.M.; Donis-Keller, H.; Langer, J.C.

    1994-09-01

    Hirschsprung`s disease (HSCR, aganglionic megacolon) is characterized by a lack of ganglion cells along variable lengths of the hindgut. This is most likely due to a failure of the progenitor cells (that are destined to become the ganglion cells of the submucosal and myenteric plexuses) to complete their distal migration in the colon. Recently, mutations in the RET protoocogene have been reported in association with HSCR. We report a novel nonsense mutation resulting in a severely truncated protein. Germline DNA from a panel of 6 HSCR patients was analyzed by SSCP for 20 exons of RET. Eight exons were also directly sequenced. We identified a novel mutation within RET exon 2. The mutation (TAC{sub 36}{yields}TAG{sub 36}), which occurs at nucleotide position 108, involves the replacement of tyrosine with a stop codon and results in a truncated 35 amino acid protein. This mutation is the most 5{prime} nonsense mutation reported thus far. Interestingly, the patient has no prior family history of HSCR and was also diagnosed with multiple developmental anomalies including dysplastic kidney. Recent gene targeting studies with mouse models have shown that RET is essential for normal renal development. However, a parallel phenotype has not been seen in other reported HSCR patients with RET mutations. The observations reported here provide evidence that RET plays a role in human renal development. Ongoing studies will determine the extent of RET involvement in sporadic cases of HSCR.

  11. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

    PubMed Central

    Beilina, Alexandria; Rudenko, Iakov N.; Kaganovich, Alice; Civiero, Laura; Chau, Hien; Kalia, Suneil K.; Kalia, Lorraine V.; Lobbestael, Evy; Chia, Ruth; Ndukwe, Kelechi; Ding, Jinhui; Nalls, Mike A.; Olszewski, Maciej; Hauser, David N.; Kumaran, Ravindran; Lozano, Andres M.; Baekelandt, Veerle; Greene, Lois E.; Taymans, Jean-Marc; Greggio, Elisa; Cookson, Mark R.; Nalls, Mike A.; Plagnol, Vincent; Martinez, Maria; Hernandez, Dena G; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simón-Sánchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M A; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M; Brockmann, Kathrin; Brooks, Janet; Burn, David J; Charlesworth, Gavin; Chen, Honglei; Chong, Sean; Clarke, Carl E; Cookson, Mark R; Cooper, J Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T; van Dijk, Karin D; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gibbs, J Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Ómar; Harris, Clare; van Hilten, Jacobus J; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E; Huttenlocher, Johanna; Illig, Thomas; München, Helmholtz Zentrum; Jónsson, Pálmi V; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; München, Helmholtz Zentrum; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R; Morrison, Karen E; Mudanohwo, Ese; O’Sullivan, Sean S; Pearson, Justin; Perlmutter, Joel S; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C A; Stefánsson, Hreinn; Steinberg, Stacy; Stockton, Joanna D; Strange, Amy; Talbot, Kevin; Tanner, Carlie M; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J; Uitterlinden, André G; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H; Winder-Rhodes, Sophie; Stefánsson, Kári; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Singleton, Andrew B; Wood, Nicholas W; Chinnery, Patrick F; Arepalli, Sampath; Cookson, Mark R; Dillman, Allissa; Ferrucci, Luigi; Gibbs, J Raphael; Hernandez, Dena G; Johnson, Robert; Longo, Dan L; Majounie, Elisa; Nalls, Michael A; O’Brien, Richard; Singleton, Andrew B; Traynor, Bryan J; Troncoso, Juan; van der Brug, Marcel; Zielke, H Ronald; Zonderman, Alan B

    2014-01-01

    Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein–protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G–associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy–lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms. PMID:24510904

  12. The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients.

    PubMed

    Moore, Roger A; Head, Mark W; Ironside, James W; Ritchie, Diane L; Zanusso, Gianluigi; Choi, Young Pyo; Pyo Choi, Young; Priola, Suzette A

    2016-02-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C)) into infectious PrP(Sc). By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrP(Sc). In both forms of CJD, heterozygosity at residue 129 for methionine (M) or valine (V) in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrP(C) allotype to PrP(Sc) in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrP(Sc) with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrP(C) containing an M or V at residue 129 having a similar propensity to misfold into PrP(Sc) thus causing sCJD. By contrast, PrP(Sc) with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrP(Sc) containing V at residue 129. In both types of CJD, the PrP(Sc) allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrP(Sc) allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD.

  13. The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients

    PubMed Central

    Moore, Roger A.; Head, Mark W.; Ironside, James W.; Ritchie, Diane L.; Zanusso, Gianluigi; Pyo Choi, Young; Priola, Suzette A.

    2016-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrPSc). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrPC) into infectious PrPSc. By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrPSc. In both forms of CJD, heterozygosity at residue 129 for methionine (M) or valine (V) in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrPC allotype to PrPSc in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrPSc with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrPC containing an M or V at residue 129 having a similar propensity to misfold into PrPSc thus causing sCJD. By contrast, PrPSc with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrPSc containing V at residue 129. In both types of CJD, the PrPSc allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrPSc allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD. PMID:26840342

  14. Structure and sources of the sporadic meteor background from video observations

    NASA Astrophysics Data System (ADS)

    Jakšová, Ivana; Porubčan, Vladimír; Klačka, Jozef

    2015-10-01

    We investigate and discuss the structure of the sporadic meteor background population in the near-Earth space based on video meteor orbits from the SonotaCo database (SonotaCo 2009, WGN, 37, 55). The selection of the shower meteors was done by the Southworth-Hawkins streams-search criterion (Southworth & Hawkins 1963, Smithson. Contr. Astrophys., 7, 261). Of a total of 117786 orbits, 69.34% were assigned to sporadic background meteors. Our analysis revealed all the known sporadic sources, such as the dominant apex source which is splitting into the northern and southern branch. Part of a denser ring structure about the apex source connecting the antihelion and north toroidal sources is also evident. We showed that the annual activity of the apex source is similar to the annual variation in activity of the whole sporadic background. The antihelion source exhibits a very broad maximum from July until January and the north toroidal source shows three maxima similar to the radar observations by the Canadian Meteor Orbit Radar (CMOR). Potential parent bodies of the sporadic population were searched for by comparison of the distributions of the orbital elements of sporadic meteors, minor planets and comets.

  15. Sporadic mortality in chronic toxicity tests using Pimephales promelas (Rafinesque): Cases of characterization and control

    SciTech Connect

    Downey, P.J.; Fleming, K.; Guinn, R.; Chapman, N.; Varner, P.; Cooney, J.D.

    2000-01-01

    In whole effluent toxicity tests, organisms are exposed to various effluent concentrations for a specific time period to estimate the potential effects of an effluent on a receiving stream. Laboratories typically have good success performing valid chronic toxicity tests. However, some difficulty in conducting valid chronic whole effluent toxicity tests with Pimephales promelas (fathead minnow) has been encountered as a result of sporadic control mortality. Some investigators report an interference that causes anomalous patterns of survival in chronic fathead minnow tests. This interference has been termed sporadic mortality phenomenon. Characteristics of sporadic mortality phenomenon include high variability among replicates, nonmonotonic dose responses, mortality beginning on or about day 4 of the test, and fungal growths often observed on the larvae. Histopathologic examinations often indicate bacterial and/or fungal infections on fish exhibiting symptoms of sporadic mortality phenomenon. The most plausible explanation of sporadic mortality phenomenon is a naturally occurring pathogen or pathogens that interfere with the test method. This interference may invalidate tests or falsely indicate toxicity. Sporadic mortality phenomenon can be reduced or eliminated by sample treatments intended to inactivate (heating, antibiotics, or ultraviolet light) or remove (filtration) pathogenic microorganisms. These methods must be used with forethought because of their potential to alter the toxicity of a sample.

  16. Mendelian genes for Parkinson's disease contribute to the sporadic forms of the disease.

    PubMed

    Spataro, Nino; Calafell, Francesc; Cervera-Carles, Laura; Casals, Ferran; Pagonabarraga, Javier; Pascual-Sedano, Berta; Campolongo, Antònia; Kulisevsky, Jaime; Lleó, Alberto; Navarro, Arcadi; Clarimón, Jordi; Bosch, Elena

    2015-04-01

    Parkinson's disease (PD) can be divided into familial (Mendelian) and sporadic forms. A number of causal genes have been discovered for the Mendelian form, which constitutes 10-20% of the total cases. Genome-wide association studies have successfully uncovered a number of susceptibility loci for sporadic cases but those only explain a small fraction (6-7%) of PD heritability. It has been observed that some genes that confer susceptibility to PD through common risk variants also contain rare causing mutations for the Mendelian forms of the disease. These results suggest a possible functional link between Mendelian and sporadic PD and led us to investigate the role that rare and low-frequency variants could have on the sporadic form. Through a targeting approach, we have resequenced at 49× coverage the exons and regulatory regions of 38 genes (including Mendelian and susceptibility PD genes) in 249 sporadic PD patients and 145 unrelated controls of European origin. Unlike susceptibility genes, Mendelian genes show a clear general enrichment of rare functional variants in PD cases, observed directly as well as with Tajima's D statistic and several collapsing methods. Our findings suggest that rare variation on PD Mendelian genes may have a role in the sporadic forms of the disease.

  17. Coincident extremely large sporadic sodium and sporadic E layers observed in the lower thermosphere over Colorado and Utah

    NASA Astrophysics Data System (ADS)

    Milikh, G. M.; Guzdar, P. N.; Sharma, S. A.; Williams, B. P.; Sherman, J.; She, C. Y.; Wright, J. W.; Zabotin, N. A.; Berkey, F. T.

    2004-05-01

    On the night of June 2, 2002, the CSU sodium lidar measured an extremely strong sporadic sodium layer lasting from 3.5 to 5 UT with several weaker layers later in the night at 6 and 9 UT. There is a double layer stucture with peaks at 101 and 104 km. The peak sodium density was 21,000 atoms/cm3 with a column abundance up to twice the normal sodium layer. The peak density was 500 times greater than the typical density at that altitude. The abundance and strength factor were higher than any reported in the literature. The two lidar beams, separated by 80km at this altitude, both measured 1 hour periodicities in the abundance, but directly out-of-phase. There is also evidence for strong wave activity in the lidar temperatures and winds. The NOAA Boulder ionosonde measured an foEs of 14.3 MHz at 3 UT on this night, the highest value during 2002. The Bear Lake, Utah dynasonde also measured intense Es between 2-5 UT and again from 6-8 UT about 700 km west of the lidar, with most of the ionograms during these intervals measuring Es up to 12 MHz, the limit of the ionosonde sweep. Other ionosondes around North America on the NGDC database measured normal foEs values that night, so it was a localized event. Using the sodium density, wind and temperature from the lidar and the ionospheric data from the ionosondes, we will investigate the formation mechanism for this extreme event.

  18. Germline and somatic mutations in cyclin-dependent kinase inhibitor genes CDKN1A, CDKN2B, and CDKN2C in sporadic parathyroid adenomas.

    PubMed

    Costa-Guda, Jessica; Soong, Chen-Pang; Parekh, Vaishali I; Agarwal, Sunita K; Arnold, Andrew

    2013-10-01

    The molecular pathogenesis of sporadic parathyroid adenomas is incompletely understood. The possible role of cyclin-dependent kinase inhibitor (CDKI) genes was raised by recognition of cyclin D1 as a parathyroid oncogene, identification of rare germline mutations in CDKI genes in patients with multiple endocrine neoplasia type 1; that in rodents, mutation in Cdkn1b caused parathyroid tumors; and subsequently through identification of rare predisposing germline sequence variants and somatic mutation of CDKN1B, encoding p27(kip1), in sporadic human parathyroid adenoma. We therefore sought to determine whether mutations/variants in the other six CDKI genes CDKN1A, CDKN1C, CDKN2A, CDKN2B, CDKN2C, and CDKN2D, encoding p21, p57, p14(ARF)/p16, p15, p18, and p19, respectively, contribute to the development of typical parathyroid adenomas. In a series of 85 sporadic parathyroid adenomas, direct DNA sequencing identified alterations in five adenomas (6 %): Two contained distinct heterozygous changes in CDKN1A, one germline and one of undetermined germline status; one had a CDKN2B germline alteration, accompanied by loss of the normal allele in the tumor (LOH); two had variants of CDKN2C, one somatic and one germline with LOH. Abnormalities of three of the mutant proteins were readily demonstrable in vitro. Thus, germline mutations/rare variants in CDKN1A, CDKN2B, and CDKN2C likely contribute to the development of a significant subgroup of common sporadic parathyroid adenomas, and somatic mutation in CDKN2C further suggests a direct role for CDKI alteration in conferring a selective growth advantage to parathyroid cells, providing novel support for the concept that multiple CDKIs can play primary roles in human neoplasia.

  19. Sporadic colorectal cancer: Studying ways to an end

    PubMed Central

    Fidalgo, Paulo; Filipe, Bruno; Albuquerque, Cristina; Fonseca, Ricardo; Chaves, Paula; Pereira, António D

    2015-01-01

    Introduction Although colorectal cancer (CRC) has often been regarded as a single entity, different pathways may lead to macroscopically similar cancers. These pathways may evolve into a patchy colonic field defect that we aimed to study in consecutive CRC patients. Methods In a single-center, observational, prospective study, consecutive CRC patients were included if surgery and a perioperative colonoscopy were planned. Personal and familial history data were collected. Tumors were studied for microsatellite instability (MSI) status, DNA repair protein expression (DRPE) and presence of BRAF and/or APC mutations. Macroscopically normal mucosa samples were tested for APC mutations. Presence and location of synchronous and metachronous adenomas and patient follow-up were analyzed. The association of two categorical variables was tested through the Fisher’s exact test (SPSS 19). Results Twenty-four patients (12 male, mean age 69 years) were studied. High-grade MSI (MSI-H) was found in eight tumors—these were significantly more common in the right colon (p = 0.047) and more likely to have an altered DRPE (p = 0.007). BRAF mutation was found in two of six tested MSI-H tumors. APC gene mutations were found in nine of 16 non-MSI-H tumors and absent in normal mucosa samples. There was a nonsignificant co-localization of CRC and synchronous adenomas and a significant co-localization (p = 0.05) of synchronous and metachronous adenomas. Discussion Sporadic CRCs evolve through distinct pathways, evidenced only by pathological and molecular analysis, but clinically relevant both for patients and their families. In non-MSI-H tumors, the expected APC gene mutations were not detected by the most commonly used techniques in a high number of cases. More studies are needed to fully characterize these tumors and to search for common early events in normal mucosa patches, which might explain the indirect evidence found here for a field defect in the colon. PMID:27087959

  20. Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

    PubMed Central

    Correia-Deur, Joya Emilie M.; Toledo, Rodrigo A.; Imazawa, Alice T.; Lourenço, Delmar M.; Ezabella, Marilza C. L.; Tavares, Marcos R.; Toledo, Sergio P. A.

    2009-01-01

    INTRODUCTION: Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS: The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6–15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were

  1. Sporadic E Morphology from GPS-CHAMP Radio Occultation

    NASA Technical Reports Server (NTRS)

    Wu, Dong L.; Ao, Chi O.; Hajj, George A.; de la Torre Juarez, Manuel; Mannucci, Anthony J.

    2005-01-01

    The scintillations of phase and amplitude in terms of signal-to-noise ratio (SNR) of the GPS radio occultation signal are caused by thin ionization layers. These thin irregular electron density layers in the E region ionosphere are often called sporadic E (Es). For a monthly retrieval of Es morphology we use the variances of the phase and SNR fluctuations of worldwide 6000 GPS/CHAMP occultations in the E region. The Es climatology is studied globally with the SNR and phase variances in terms of monthly zonal means, seasonal maps, and diurnal and long-term variations. The zonal mean variances reveal strong, extended Es activities at summertime midlatitudes but weak, confined activities in wintertime high latitudes, peaking at 105 km. Global maps at 105-km altitude show clear dependence of Es activities on the geomagnetic dip angle, where the summertime midlatitude Es occurs mostly at dip angles of 30 deg. - 60 deg. and the wintertime high-latitude enhancement occurs mostly at dip angles greater than 80 deg. The midlatitude Es variances exhibit a strong semidiurnal variation with peak hours near 0800 1000 and 2000 local solar time, respectively. The peak hours are delayed slightly with decreasing height, suggesting influences from the semidiurnal tide. To provide more insights on the observed SNR and phase variances, we model radio wave propagation for the CHAMP observing geometry under several perturbed cases in the E region ionosphere. The model simulations indicate that the SNR variance has the maximum response to Es perturbations at vertical wavelengths of 1.2 km, whereas the phase response maximizes at 2 km (for the 1-s variance analysis). The characteristic scale depends little on the truncation time used in the SNR variance analysis, but it increases with the truncation time for the phase variances. Initial studies show that reasonable global Es morphology can be produced on a monthly and seasonal basis with the CHAMP one-antenna occultations. Better results

  2. Forensic facial approximation assessment: can application of different average facial tissue depth data facilitate recognition and establish acceptable level of resemblance?

    PubMed

    Herrera, Lara Maria; Strapasson, Raíssa Ananda Paim; da Silva, Jorge Vicente Lopes; Melani, Rodolfo Francisco Haltenhoff

    2016-09-01

    Facial soft tissue thicknesses (FSTT) are important guidelines for modeling faces from skull. Amid so many FSTT data, Forensic artists have to make a subjective choice of a dataset that best meets their needs. This study investigated the performance of four FSTT datasets in the recognition and resemblance of Brazilian living individuals and the performance of assessors in recognizing people, according to sex and knowledge on Human Anatomy and Forensic Dentistry. Sixteen manual facial approximations (FAs) were constructed using three-dimensional (3D) prototypes of skulls (targets). The American method was chosen for the construction of the faces. One hundred and twenty participants evaluated all FAs by means of recognition and resemblance tests. This study showed higher proportions of recognition by FAs conducted with FSTT data from cadavers compared with those conducted with medical imaging data. Targets were also considered more similar to FAs conducted with FSTT data from cadavers. Nose and face shape, respectively, were considered the most similar regions to targets. The sex of assessors (male and female) and the knowledge on Human Anatomy and Forensic Dentistry did not play a determinant role to reach greater recognition rates. It was possible to conclude that FSTT data obtained from imaging may not facilitate recognition and establish acceptable level of resemblance. Grouping FSTT data by regions of the face, as proposed in this paper, may contribute to more accurate FAs.

  3. Necrotizing meningoencephalitis of Pug dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis.

    PubMed

    Greer, K A; Wong, A K; Liu, H; Famula, T R; Pedersen, N C; Ruhe, A; Wallace, M; Neff, M W

    2010-08-01

    Necrotizing meningoencephalitis (NME) is a disorder of Pug Dogs that appears to have an immune etiology and high heritability based on population studies. The present study was undertaken to identify a genetic basis for the disease. A genome-wide association scan with single tandem repeat (STR) markers showed a single strong association near the dog leukocyte antigen (DLA) complex on CFA12. Fine resolution mapping with 27 STR markers on CFA12 further narrowed association to the region containing DLA-DRB1, -DQA1 and, -DQB1 genes. Sequencing confirmed that affected dogs were more likely to be homozygous for specific alleles at each locus and that these alleles were linked, forming a single high risk haplotype. The strong DLA class II association of NME in Pug Dogs resembles that of human multiple sclerosis (MS). Like MS, NME appears to have an autoimmune basis, involves genetic and nongenetic factors, has a relatively low incidence, is more frequent in females than males, and is associated with a vascularly orientated nonsuppurative inflammation. However, NME of Pug Dogs is more aggressive in disease course than classical human MS, appears to be relatively earlier in onset, and involves necrosis rather than demyelination as the central pathobiologic feature. Thus, Pug Dog encephalitis (PDE) shares clinical features with the less common acute variant forms of MS. Accordingly, NME of Pug Dogs may represent a naturally occurring canine model of certain idiopathic inflammatory disorders of the human central nervous system.

  4. A Family Resemblance Approach to the Nature of Science for Science Education

    NASA Astrophysics Data System (ADS)

    Irzik, Gürol; Nola, Robert

    2011-07-01

    Although there is universal consensus both in the science education literature and in the science standards documents to the effect that students should learn not only the content of science but also its nature, there is little agreement about what that nature is. This led many science educators to adopt what is sometimes called "the consensus view" about the nature of science (NOS), whose goal is to teach students only those characteristics of science on which there is wide consensus. This is an attractive view, but it has some shortcomings and weaknesses. In this article we present and defend an alternative approach based on the notion of family resemblance. We argue that the family resemblance approach is superior to the consensus view in several ways, which we discuss in some detail.

  5. Gastrointestinal symptoms resembling ulcerative proctitis caused by larvae of the drone fly Eristalis tenax

    PubMed Central

    Desoubeaux, Guillaume; Gaillard, Julien; Borée-Moreau, Diane; Bailly, Éric; Andres, Christian R; Chandenier, Jacques

    2014-01-01

    We report a case of facultative intestinal myiasis due to larvae of the drone fly Eristalis tenax, also named the rat-tailed maggots. The development of larvae in the lower bowel was responsible for non-specific gastrointestinal symptoms that resembled ulcerative proctitis. The diagnosis was established upon the observation of four spontaneously excreted mobile larvae. The definite identification of the E. tenax species was made possible by scanning electron microscopy. The clinical outcome was satisfactory. PMID:24766340

  6. Gastrointestinal symptoms resembling ulcerative proctitis caused by larvae of the drone fly Eristalis tenax.

    PubMed

    Desoubeaux, Guillaume; Gaillard, Julien; Borée-Moreau, Diane; Bailly, Éric; Andres, Christian R; Chandenier, Jacques

    2014-04-01

    We report a case of facultative intestinal myiasis due to larvae of the drone fly Eristalis tenax, also named the rat-tailed maggots. The development of larvae in the lower bowel was responsible for non-specific gastrointestinal symptoms that resembled ulcerative proctitis. The diagnosis was established upon the observation of four spontaneously excreted mobile larvae. The definite identification of the E. tenax species was made possible by scanning electron microscopy. The clinical outcome was satisfactory.

  7. Identification of Anthrax Toxin Genes in a Bacillus cereus Associated With An Illness Resembling Inhalation Anthrax

    DTIC Science & Technology

    2004-01-01

    Identification of anthrax toxin genes in a Bacillus cereus associated with an illness resembling inhalation anthrax Alex R. Hoffmaster*†, Jacques... Bacillus anthracis is the etiologic agent of anthrax, an acute fatal disease among mammals. It was thought to differ from Bacillus cereus , an...correlation of phenotypic characteristics and their genetic basis. Bacillus cereus and Bacillus anthracis are members of a closelyrelated phylogenetic

  8. Familial resemblance for VO2max in the sedentary state: the HERITAGE family study.

    PubMed

    Bouchard, C; Daw, E W; Rice, T; Pérusse, L; Gagnon, J; Province, M A; Leon, A S; Rao, D C; Skinner, J S; Wilmore, J H

    1998-02-01

    This study investigates the familial resemblance of maximal oxygen uptake (VO2max) based on data from 86 nuclear families of Caucasian descent participating in the HERITAGE Family Study. In the current study, VO2max was measured twice on a cycle ergometer in 429 sedentary individuals (170 parents and 259 of their offspring), aged between 16 and 65 yr. The VO2max was adjusted by regression procedures for the effects of 1) age and sex; 2) age, sex, and body mass; and 3) age, sex, body mass, fat mass, and fat-free mass, as determined by underwater weighing. Evidence for significant familial resemblance was observed for each of the three VO2max phenotypes. Spouse, sibling, and parent-offspring correlations were significant, suggesting that both genetic and environmental factors contribute to the familial resemblance for VO2max. Maximal heritability estimates were at least 50%, a value inflated to an undetermined degree by nongenetic factors. The hypothesis of maternal inheritance, with the father's contribution being environmental, was also found to fit the data with estimates of maternal heritability, potentially associated in part with mitochondrial inheritance, reaching about 30%. These results suggest that genetic and nongenetic factors as well as maternal influences contribute to the familial aggregation of VO2max in sedentary individuals.

  9. Early Detection of Epidemic GII-4 Norovirus Strains in UK and Malawi: Role of Surveillance of Sporadic Acute Gastroenteritis in Anticipating Global Epidemics

    PubMed Central

    Callaghan, Anna; O’Brien, Sarah J.; Cunliffe, Nigel A.; Iturriza-Gómara, Miren

    2016-01-01

    Noroviruses are endemic in the human population, and are recognised as a leading cause of acute gastroenteritis worldwide. Although they are a highly diverse group of viruses, genogroup-II genotype-4 (GII-4) noroviruses are the most frequently identified strains worldwide. The predominance of GII-4 norovirus strains is driven by the periodic emergence of antigenic variants capable of evading herd protection. The global molecular epidemiology of emerging GII-4 strains is largely based on data from outbreak surveillance programmes, but the epidemiology of GII-4 strains among sporadic or community cases is far less well studied. To understand the distribution of GII-4 norovirus strains associated with gastroenteritis in the wider population, we characterised the GII-4 norovirus strains detected during studies of sporadic cases of infectious gastroenteritis collected in the UK and Malawi between 1993 and 2009. Our data shows that GII-4 norovirus strains that have emerged as strains of global epidemic importance have circulated in the community up to 18 years before their recognition as pandemic strains associated with increases in outbreaks. These data may suggest that more comprehensive surveillance programmes that incorporate strains associated with sporadic cases may provide a way for early detection of emerging strains with pandemic potential. This may be of particular relevance as vaccines become available. PMID:27115152

  10. Sporadic Visual Acuity Loss in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)

    PubMed Central

    Kim, Benjamin J.; Ying, Gui-Shuang; Huang, Jiayan; Levy, Nicole E.; Maguire, Maureen G.

    2014-01-01

    Purpose To evaluate transient, large visual acuity (VA) decreases, termed sporadic vision loss, during anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration (AMD). Design Cohort within a randomized clinical trial. Methods Setting Comparison of AMD Treatments Trials (CATT). Study Population 1185 CATT patients. Main Outcome Measures incidence of sporadic vision loss and odds ratio (OR) for association with patient and ocular factors. Sporadic vision loss was a decline of ≥ 15 letters from the previous visit, followed by a return at the next visit to no more than 5 letters worse than the visit before the VA loss. Results There were 143 sporadic vision loss events in 122/1185 (10.3%) patients. Mean VA at two years for those with and without sporadic vision loss was 58.5 (~20/63) and 68.4 (~20/40) letters, respectively (P < 0.001). Among patients treated pro re nata, no injection was given for 27.6% (27/98) of sporadic vision loss events. Multivariate analysis demonstrated that baseline predictors for sporadic vision loss included worse baseline VA (OR 2.92, 95%CI:1.65–5.17 for ≤ 20/200 compared with ≥ 20/40), scar (OR 2.21, 95%CI:1.22–4.01), intraretinal foveal fluid on optical coherence tomography (OR 1.80, 95%CI:1.11–2.91), and medical history of anxiety (OR 1.90, 95%CI:1.12–3.24) and syncope (OR 2.75, 95%CI:1.45–5.22). Refraction decreased the likelihood of sporadic vision loss (OR 0.62, 95%CI:0.42–0.91). Conclusions Approximately 10% of CATT patients had sporadic vision loss. Baseline predictors included AMD-related factors and factors independent of AMD. These data are relevant for clinicians in practice and those involved in clinical trials. PMID:24727261

  11. De novo TBR1 mutations in sporadic autism disrupt protein functions

    PubMed Central

    Deriziotis, Pelagia; O’Roak, Brian J.; Graham, Sarah A.; Estruch, Sara B.; Dimitropoulou, Danai; Bernier, Raphael A.; Gerdts, Jennifer; Shendure, Jay; Eichler, Evan E.; Fisher, Simon E.

    2014-01-01

    Next-generation sequencing recently revealed that recurrent disruptive mutations in a few genes may account for 1% of sporadic autism cases. Coupling these novel genetic data to empirical assays of protein function can illuminate crucial molecular networks. Here we demonstrate the power of the approach, performing the first functional analyses of TBR1 variants identified in sporadic autism. De novo truncating and missense mutations disrupt multiple aspects of TBR1 function, including subcellular localization, interactions with co-regulators and transcriptional repression. Missense mutations inherited from unaffected parents did not disturb function in our assays. We show that TBR1 homodimerizes, that it interacts with FOXP2, a transcription factor implicated in speech/language disorders, and that this interaction is disrupted by pathogenic mutations affecting either protein. These findings support the hypothesis that de novo mutations in sporadic autism have severe functional consequences. Moreover, they uncover neurogenetic mechanisms that bridge different neurodevelopmental disorders involving language deficits. PMID:25232744

  12. Case-control studies of sporadic cryptosporidiosis in Melbourne and Adelaide, Australia.

    PubMed Central

    Robertson, B.; Sinclair, M. I.; Forbes, A. B.; Veitch, M.; Kirk, M.; Cunliffe, D.; Willis, J.; Fairley, C. K.

    2002-01-01

    Few studies have assessed risk factors for sporadic cryptosporidiosis in industrialized countries, even though it may be numerically more common than outbreaks of disease. We carried out case-control studies assessing risk factors for sporadic disease in Melbourne and Adelaide, which have water supplies from different ends of the raw water spectrum. In addition to examining drinking water, we assessed several other exposures. 201 cases and 795 controls were recruited for Melbourne and 134 cases and 536 controls were recruited for Adelaide. Risk factors were similar for the two cities, with swimming in public pools and contact with a person with diarrhoea being most important. The consumption of plain tap water was not found to be associated with disease. This study emphasizes the need for regular public health messages to the public and swimming pool managers in an attempt to prevent sporadic cryptosporidiosis, as well as outbreaks of disease. PMID:12113486

  13. Genetic Cross-Interaction between APOE and PRNP in Sporadic Alzheimer's and Creutzfeldt-Jakob Diseases

    PubMed Central

    Calero, Olga; Bullido, María J.; Clarimón, Jordi; Frank-García, Ana; Martínez-Martín, Pablo; Lleó, Alberto; Rey, María Jesús; Rábano, Alberto; Blesa, Rafael; Gómez-Isla, Teresa; Valdivieso, Fernando; de Pedro-Cuesta, Jesús; Ferrer, Isidro; Calero, Miguel

    2011-01-01

    Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) represent two distinct clinical entities belonging to a wider group, generically named as conformational disorders that share common pathophysiologic mechanisms. It is well-established that the APOE ε4 allele and homozygosity at polymorphic codon 129 in the PRNP gene are the major genetic risk factors for AD and human prion diseases, respectively. However, the roles of PRNP in AD, and APOE in CJD are controversial. In this work, we investigated for the first time, APOE and PRNP genotypes simultaneously in 474 AD and 175 sporadic CJD (sCJD) patients compared to a common control population of 335 subjects. Differences in genotype distribution between patients and control subjects were studied by logistic regression analysis using age and gender as covariates. The effect size of risk association and synergy factors were calculated using the logistic odds ratio estimates. Our data confirmed that the presence of APOE ε4 allele is associated with a higher risk of developing AD, while homozygosity at PRNP gene constitutes a risk for sCJD. Opposite, we found no association for PRNP with AD, nor for APOE with sCJD. Interestingly, when AD and sCJD patients were stratified according to their respective main risk genes (APOE for AD, and PRNP for sCJD), we found statistically significant associations for the other gene in those strata at higher previous risk. Synergy factor analysis showed a synergistic age-dependent interaction between APOE and PRNP in both AD (SF = 3.59, p = 0.027), and sCJD (SF = 7.26, p = 0.005). We propose that this statistical epistasis can partially explain divergent data from different association studies. Moreover, these results suggest that the genetic interaction between APOE and PRNP may have a biological correlate that is indicative of shared neurodegenerative pathways involved in AD and sCJD. PMID:21799773

  14. UNC13A confers risk for sporadic ALS and influences survival in a Spanish cohort.

    PubMed

    Vidal-Taboada, Jose Manuel; Lopez-Lopez, Alan; Salvado, Maria; Lorenzo, Laura; Garcia, Cecilia; Mahy, Nicole; Rodríguez, Manuel J; Gamez, Josep

    2015-10-01

    To investigate the association of functional variants of the human UNC13A gene with the risk of ALS, survival and the disease progression rate in a Spanish ALS cohort. 136 sporadic ALS (sALS) patients and 487 healthy controls were genotyped for the UNC13A rs12608932 variant. Clinical characterization of ALS patients included gender, age at first symptom, initial topography, disease progression rate, and survival. Genetic association was analyzed under five inheritance models. The sALS patients with the rs12608932(CC) genotype had an increased risk of ALS under a recessive genetic model [OR 2.16; 95 % CI (1.23, 3.8), p = 0.009; corrected p = 0.028]. Genotypes with a C allele are also associated with increased risk [OR 1.47; 95 % CI (1.11, 1.95); p = 0.008; corrected p = 0.023] under an additive model. sALS patients with a C/C genotype had a shorter survival than patients with A/A and A/C genotypes [HR 1.44; 95 % CI (1.11, 1.873); p = 0.007] under a recessive model. In an overdominant model, heterozygous patients had a longer survival than homozygous patients [HR 0.36; 95 % CI (0.22, 0.59); p = 0.001]. The rs12608932 genotypes modify the progression of symptoms measured using the ALSFRS-R. No association with age of onset, initial topography or rate of decline in FVC was found. Our results show that rs12608932 is a risk factor for ALS in the Spanish population and replicate the findings described in other populations. The rs12608932 is a modifying factor for survival and disease progression rate in our series. Our results also corroborated that it did not influence the age of onset.

  15. Characterization of hepatitis E virus from outbreak and sporadic cases in Turkmenistan.

    PubMed

    Albetkova, Adilya; Drobeniuc, Jan; Yashina, Tatiana; Musabaev, Erkin; Robertson, Betty; Nainan, Omana; Favorov, Michael

    2007-11-01

    Large outbreaks and sporadic cases of hepatitis E have been reported in Central Asia. We assessed the genetic relatedness of hepatitis E virus (HEV) strains from outbreak and sporadic cases in Turkmenistan. Specimens from outbreak and sporadic cases of acute hepatitis non-A, non-B were tested by reverse transcription (RT)-polymerase chain reaction (PCR) to identify the presence of HEV RNA; nucleotide sequences were analyzed. HEV RNA was detected from 23/156 (15%) outbreak cases and 2/23 (9%) sporadic cases. The HEV outbreak isolates represented 14 unique sequences with genetic distances varying between 0.3% and 8.6%, 12 of which were closely related, with distances between 0.3% and 5.6%. Two unique sequences from outbreak cases 32 and 42 were closely related (99.7%) and shared 91.8-93.4% of sequence with the other 12 strains. The two strains were closely related to the previously published isolates from Burma (99.7-100%) and India-Madras (95.7-96.1%). The two 1994 sporadic HEV strains were 97.4% distinct, wile revealing 91.4-94.1% homology to 1985 strains, and 94.4-94.7% to HEV from the neighboring China and Pakistan. Genetic diversity of HEV that caused the hepatitis E outbreak in Turkmenistan in 1985 suggests heterogeneity of viral sources. Sporadic hepatitis E that occurred in 1994 was caused by viral strains genetically distinct from those causing the outbreak in 1985, yet closely related to HEV from neighboring countries. The study suggests that circulation of a broad variety of strains of HEV may occur in Central Asia, regardless of international borders, presenting a significant public health threat to the population of the region.

  16. [Characteristics of bacteria in the genus Proteus isolated from patients with sporadic and group intestinal diseases].

    PubMed

    Apollonin, A V; Romanenko, E E; Iorzh, A L; Zueva, L P

    1985-02-01

    The biochemical and biological properties of 148 Proteus strains isolated from patients both in sporadic intestinal infections and in a case of group infection in children's hospital was studied. The study revealed that the etiological factor of the group infection was P. mirabilis belonging to rare serovar 48:2. Proteus organisms isolated in sporadic infections belonged to a great number of serovars. No relationship between the isolated serovar and the nosological form of the intestinal disease was established. Among the Proteus strains under study, 82 strains showed atypical biochemical properties in 1 test or more. No correlation between the clinical diagnosis and the occurrence of atypical strains was established.

  17. Multibubble Sonoluminescence Spectra of Water which Resemble Single-Bubble Sonoluminescence

    NASA Astrophysics Data System (ADS)

    Didenko, Y. T.; Gordeychuk, T. V.

    2000-06-01

    Multibubble sonoluminescence (MBSL) spectra of water from cavitation clouds were collected in the presence of different noble gases and at different acoustic intensities. Results show that at high acoustic intensity and with xenon as a dissolved gas the emission of the OH* radical becomes indiscernible from the continuum. These spectra resemble single-bubble sonoluminescence (SBSL) spectra. It is concluded that the source of emission in MBSL and SBSL can be the same, the difference in spectra is due to the higher temperature inside the bubble during SBSL.

  18. Multibubble sonoluminescence spectra of water which resemble single-bubble sonoluminescence

    PubMed

    Didenko; Gordeychuk

    2000-06-12

    Multibubble sonoluminescence (MBSL) spectra of water from cavitation clouds were collected in the presence of different noble gases and at different acoustic intensities. Results show that at high acoustic intensity and with xenon as a dissolved gas the emission of the OH* radical becomes indiscernible from the continuum. These spectra resemble single-bubble sonoluminescence (SBSL) spectra. It is concluded that the source of emission in MBSL and SBSL can be the same, the difference in spectra is due to the higher temperature inside the bubble during SBSL.

  19. Dermatitis and lymphadenitis resembling juvenile cellulitis in a four-year-old dog.

    PubMed

    Neuber, A E; van den Broek, A H M; Brownstein, D; Thoday, K L; Hill, P B

    2004-05-01

    A four-year-old, entire male toy poodle was presented with a two-and-a-half-week history of ocular discharge progressing to periorbital alopecia, depigmentation, alopecia and ulceration around the muzzle. There was also a haemorrhagic discharge from the ears, pyrexia, lethargy and generalised lymphadenopathy. The clinical, cytological, bacteriological and histopathological findings were consistent with a diagnosis of dermatitis resembling juvenile cellulitis in an adult dog. Glucocorticoid therapy led to rapid resolution of the clinical signs and the dog has remained in remission for two years after cessation of treatment.

  20. Purple, stiff lesions resembling varicose veins on lower limb: certainly consider Kaposi sarcoma

    PubMed Central

    Arslan, Gokhan; Cicek, Ali Fuat; Oz, Bilgehan Savas

    2016-01-01

    Kaposi’s sarcoma (KS) typically presents multiple cutaneous lesions of the lower extremities. Lesions can rarely mimic varicose veins without venous insufficiency, vascular or stasis ulcers. As the initial diagnosis of KS is generally determined clinically, a high index of suspicion and palpation of lesions are necessary for all patients with atypical presentations of varicose-like lesions of lower extremities. Tissue biopsy with histological analysis is essential for all uncertain lesions. This is a case of KS occurring in a 79-year-old man who presented with indurated vascular plaques resembling varicose veins on the right foot. PMID:28096842

  1. Right atrial aneurysm with downward displacement of the anterior leaflet that resembled Ebstein's anomaly.

    PubMed

    Yamauchi, Sanae; Suzuki, Yasuyuki; Daitoku, Kazuyuki; Kimura, Masaomi; Okumura, Ken; Fukuda, Ikuo

    2016-06-08

    A 13-year-old boy presented with right atrial aneurysm and downward displacement of the anterior leaflet in the tricuspid valve into the right ventricle, without tricuspid valve regurgitation. Paroxysmal atrial flutter was caused by an abnormal electrical re-entry circuit, which could not be treated using catheter radiofrequency ablation. Therefore, the patient underwent surgical ablation and resection of the enlarged right atrial wall. The anterior leaflet of the tricuspid valve was plastered and displaced downward into the right ventricle, which resembled Ebstein's anomaly. Pathological evaluation revealed a thin wall that contained fibrous tissue with lipomatous degeneration and few muscular elements. No postoperative arrhythmia was observed.

  2. Spectral transformation of the unusual variable star MWC560 to resemble a nova

    NASA Technical Reports Server (NTRS)

    Maran, Stephen P.; Michalitsianos, Andrew G.; Oliversen, Ronald J.; Sonneborn, George

    1991-01-01

    A dramatic change has occurred in the ultraviolet spectrum of the emission-line star MWC560, so that it now closely resembles the spectrum of a nova shortly after outburst. This event may signal a major mass-ejection episode such as presumably occurred in past centuries in the symbiotic star R Aquarii to produce the well-known bipolar nebula, and it may herald the emergence of a standard symbiotic-star emission-line spectrum in MWC560, corresponding to a change in evolutionary state.

  3. Statins in the chemoprevention of colorectal cancer in established animal models of sporadic and colitis-associated cancer.

    PubMed

    Pikoulis, Emmanouil; Margonis, Georgios A; Angelou, Anastasios; Zografos, George C; Antoniou, Efstathios

    2016-03-01

    Despite the availability of effective surveillance for colorectal cancer with colonoscopy, chemoprevention might be an acceptable alternative. Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins have been found to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. This systematic review aimed to gather information on the possible chemopreventive role of statins in preventing carcinogenesis and tumor promotion by a diverse array of mechanisms in both sporadic and colitis-associated cancer in animal models. The MEDLINE database was thoroughly searched using the following keywords: 'statin, HMG-CoA reductase inhibitor, colon cancer, mice, rats, chemoprevention, colitis-associated cancer'. Additional articles were gathered and evaluated. There are a lot of clinical studies and meta-analyses, as well as a plethora of basic research studies implementing cancer cell lines and animal models, on the chemopreventive role of statins in colorectal cancer (CRC). However, data derived from clinical studies are inconclusive, yet they show a tendency toward a beneficial role of statins against CRC pathogenesis. Thus, more research on the molecular pathways of CRC tumorigenesis as related to statins is warranted to uncover new mechanisms and compare the effect of statins on both sporadic and colitis-associated cancer in animal models. Basic science results could fuel exclusive colitis-associated cancer clinical trials to study the chemopreventive effects of statins and to differentiate between their effects on the two types of CRCs in humans.

  4. Expression profiles of proliferative and antiapoptotic genes in sporadic and colitis-related mouse colon cancer models

    PubMed Central

    Švec, Jiří; Ergang, Peter; Mandys, Václav; Kment, Milan; Pácha, Jiří

    2010-01-01

    Elevated levels of survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) and the regulatory factors c-MYB and Tcf-4 are often found in human cancers including colorectal cancer (CRC) and have been implicated in the development and progression of tumorigenesis. The aim of this study was to determine the expression of these genes in mouse models of sporadic and colitis-associated CRC. To address these issues, we used qRT-PCR approach to determine changes in gene expression patterns of neoplastic cells (high-grade dysplasia/intramucosal carcinoma) and surrounding normal epithelial cells in A/J and ICR mouse strains using laser microdissection. Both strains were injected with azoxymethane and ICR mice were also given drinking water that contained 2% dextran sodium sulphate. In both sporadic (A/J mice) and colitis-associated (ICR mice) models of CRC, the levels of TERT mRNA, COX-2 mRNA and Tcf-4 mRNA were higher in neoplastic cells than in surrounding normal epithelial cells. In contrast, survivin mRNA was upregulated only in neoplastic cells from A/J mice and ILK mRNA was upregulated only in neoplastic cells from ICR mice. However, the expression of iNOS mRNA was similar in normal and neoplastic cells in both models and c-MYB mRNA was actually downregulated in neoplastic cells compared with normal cells in both models. These findings suggest that the genetic background and/or the molecular mechanisms of tumorigenesis associated with genotoxic insults and colonic inflammation influence the gene expression of mTERT, COX-2, Tcf-4, c-MYB, ILK and survivin in colon epithelial neoplasia. PMID:20096072

  5. Cyproheptadine resembles clozapine in vivo following both acute and chronic administration in rats.

    PubMed

    Goudie, Andrew J; Cooper, Gillian D; Cole, Jon C; Sumnall, Harry R

    2007-03-01

    Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely. Acutely it induced full generalization in the absence of response suppression, as observed with clozapine. Chronic administration of clozapine and cyproheptadine induced tolerance and cross-tolerance respectively to the clozapine stimulus. This was characterized by circa 3.5-fold parallel shifts to the right in the clozapine generalization curves. Such tolerance and cross-tolerance was spontaneously reversible, suggesting that it was pharmacodynamic, and that clozapine and cyproheptadine induce similar neuroadaptations when administered chronically. Administration of chlordiazepoxide at a very high dose induced no cross-tolerance to the clozapine stimulus showing the pharmacological specificity of tolerance. The clozapine stimulus is a compound cue involving actions at various receptors, and various clozapine-like antipsychotic (APD) drugs generalize fully to it. These data demonstrate that in vivo cyproheptadine resembles clozapine both acutely and chronically. Our findings, in conjunction with other actions of cyproheptadine -- induction of weight gain, alleviation of clozapine withdrawal, anxiolytic actions, alleviation of 'typical' APD-induced motoric side effects, and some preliminary clinical findings -- suggest that further study of cyproheptadine in conjunction with a 'typical' APD for the possible treatment of schizophrenia is merited at both pre-clinical and clinical levels.

  6. Familial resemblance of borderline personality disorder features: genetic or cultural transmission?

    PubMed

    Distel, Marijn A; Rebollo-Mesa, Irene; Willemsen, Gonneke; Derom, Catherine A; Trull, Timothy J; Martin, Nicholas G; Boomsma, Dorret I

    2009-01-01

    Borderline personality disorder is a severe personality disorder for which genetic research has been limited to family studies and classical twin studies. These studies indicate that genetic effects explain 35 to 45% of the variance in borderline personality disorder and borderline personality features. However, effects of non-additive (dominance) genetic factors, non-random mating and cultural transmission have generally not been explored. In the present study an extended twin-family design was applied to self-report data of twins (N = 5,017) and their siblings (N = 1,266), parents (N = 3,064) and spouses (N = 939) from 4,015 families, to estimate the effects of additive and non-additive genetic and environmental factors, cultural transmission and non-random mating on individual differences in borderline personality features. Results showed that resemblance among biological relatives could completely be attributed to genetic effects. Variation in borderline personality features was explained by additive genetic (21%; 95% CI 17-26%) and dominant genetic (24%; 95% CI 17-31%) factors. Environmental influences (55%; 95% CI 51-60%) explained the remaining variance. Significant resemblance between spouses was observed, which was best explained by phenotypic assortative mating, but it had only a small effect on the genetic variance (1% of the total variance). There was no effect of cultural transmission from parents to offspring.

  7. Low-salt restructured fish products from Atlantic mackerel (Scomber scombrus) with texture resembling turkey breast.

    PubMed

    Martelo-Vidal, M J; Mesas, J M; Vázquez, M

    2012-06-01

    Atlantic mackerel (Scomber scombrus) is a pelagic and migratory species that is usually caught with other fish as bycatch. The aim of this work was to obtain low-salt restructured fish products from Atlantic mackerel resembling turkey breast using transglutaminase (0.2 U/g) as binder. NaCl concentration (0-20 g/kg), temperature (25-40 °C) and time of incubation (30-90 min) were assayed. The texture parameters (Warner-Bratzler force and Warner-Bratzler work) and expressible water were compared to those of turkey breast. Mathematical models were obtained to determine the effect of these variables on the texture of Atlantic mackerel restructured products. Optimal conditions to obtain a similar texture than turkey breast were found. The overall optimization point out that the treatment at 31.8 °C for 63.35 min using a NaCl concentration of 8.45 g/kg allowed to obtain restructured products from Atlantic mackerel with texture and expressible water similar to those of turkey breast. Color parameters (L*, a* and b*) of the product were also similar to those of turkey breast. The results showed the feasibility of producing low-salt restructured products from Atlantic mackerel resembling turkey breast using transglutaminase.

  8. Frequent isolation of Edwardsiella tarda and Pleisiomonas shigelloides from healthy Zairese freshwater fish: a possible source of sporadic diarrhea in the tropics.

    PubMed Central

    Van Damme, L R; Vandepitte, J

    1980-01-01

    The intestinal contents of 59 Zairese freshwater fish were examined for the presence of potential human enteric pathogens. Edwardsiella tarda and Plesiomonas shigelloides were isolated from 57 and 59% of them, respectively. For both microorganisms there was a significant difference between the isolation rates from lake and river fish: whereas E. tarda was much more frequently isolated from lake fish than was P. shigelloides, the reverse was observed for river fish. The authors hypothesize that sporadic cases of tropical diarrhea with E. tarda or P. shigelloides can be traced to contact with or consumption of freshwater fish. PMID:7387150

  9. Detection of infectivity in blood of persons with variant and sporadic Creutzfeldt-Jakob disease.

    PubMed

    Douet, Jean Yves; Zafar, Saima; Perret-Liaudet, Armand; Lacroux, Caroline; Lugan, Séverine; Aron, Naima; Cassard, Herve; Ponto, Claudia; Corbière, Fabien; Torres, Juan Maria; Zerr, Inga; Andreoletti, Olivier

    2014-01-01

    We report the presence of infectivity in erythrocytes, leukocytes, and plasma of 1 person with variant Creutzfeldt-Jakob disease and in the plasma of 2 in 4 persons whose tests were positive for sporadic Creutzfeldt-Jakob disease. The measured infectivity levels were comparable to those reported in various animals with transmissible spongiform encephalopathies.

  10. Observation of electron biteout regions below sporadic E layers at polar latitudes

    NASA Astrophysics Data System (ADS)

    Lehmacher, G. A.; Larsen, M. F.; Croskey, C. L.

    2015-03-01

    The descent of a narrow sporadic E layer near 95 km altitude over Poker Flat Research Range in Alaska was observed with electron probes on two consecutive sounding rockets and with incoherent scatter radar during a 2 h period near magnetic midnight. A series of four trimethyl aluminum chemical releases demonstrated that the Es layer remained just slightly above the zonal wind node, which was slowly descending due to propagating long-period gravity waves. The location of the layer is consistent with the equilibrium position due to combined action of the wind shear and electric fields. Although the horizontal electric field could not be measured directly, we estimate that it was ~ 2 mV m-1 southward, consistent with modeling the vertical ion drift, and compatible with extremely quiet conditions. Both electron probes observed deep biteout regions just below the Es enhancements, which also descended with the sporadic layers. We discuss several possibilities for the cause of these depletions; one possibility is the presence of negatively charged, nanometer-sized mesospheric smoke particles. Such particles have recently been detected in the upper mesosphere, but not yet in immediate connection with sporadic E. Our observations of electron depletions suggest a new process associated with sporadic E.

  11. FOXC2 Mutations in Familial and Sporadic Spinal Extradural Arachnoid Cyst

    PubMed Central

    Ogura, Yoji; Yabuki, Shoji; Iida, Aritoshi; Kou, Ikuyo; Nakajima, Masahiro; Kano, Hiroki; Shiina, Masaaki; Kikuchi, Shinichi; Toyama, Yoshiaki; Ogata, Kazuhiro; Nakamura, Masaya; Matsumoto, Morio; Ikegawa, Shiro

    2013-01-01

    Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that protrudes into the epidural space from a defect in the dura mater. Most cases are sporadic; however, three familial SEDAC cases have been reported, suggesting genetic etiological factors. All familial cases are associated with lymphedema-distichiasis syndrome (LDS), whose causal gene is FOXC2. However, FOXC2 mutation analysis has been performed in only 1 family, and no mutation analysis has been performed on sporadic (non-familial) SEDACs. We recruited 17 SEDAC subjects consisting of 2 familial and 7 sporadic cases and examined FOXC2 mutations by Sanger sequencing and structural abnormalities by TaqMan copy number assay. We identified 2 novel FOXC2 mutations in 2 familial cases. Incomplete LDS penetrance was noted in both families. Four subjects presented with SEDACs only. Thus, SEDAC caused by the heterozygous FOXC2 loss-of-function mutation should be considered a feature of LDS, although it often manifests as the sole symptom. Seven sporadic SEDAC subjects had no FOXC2 mutations, no symptoms of LDS, and showed differing clinical characteristics from those who had FOXC2 mutations, suggesting that other gene(s) besides FOXC2 are likely to be involved in SEDAC. PMID:24278289

  12. Characteristics of the sporadic sodium layers observed at 23 degree S

    SciTech Connect

    Batista, P.P.; Clemesha, B.R.; Batista, I.S.; Simonieh, D.M. )

    1989-11-01

    The mesospheric sodium data, obtained between 1975 and 1987 at Sao Jose dos Campos (23{degree}S,46{degree}W) with a laser radar, have been analyzed in order to identify the appearance of thin sporadic sodium layers. In this search, a total of 65 events were identified. The average height of the peaks is 95.0 km. The ratio of the maximum peak density to the average layer density is normally 2.5 to 3.0, but values as high as 7 have been observed in the most outstanding cases. The events last from a few minutes to several hours, although durations of 1-2 hours are more typical. The events occur more often during periods of large meteor showers, especially in August. The diurnal variation shows an increasing number of observed peaks from 1500 LT to midnight and remains almost constant from midnight to 0600 LT. In 52 out of 54 days for which sodium and ionsonde data are available there was an sporadic E layer nearly coincident with the sodium cloud. The coincidence is good for short-lived sporadic layers, but a substantial increase in sporadic E critical and blanketing frequencies normally precedes the long-lasting and broader ones. These results are compatible with the suggestion that the enhanced layers are produced by the wind shear distortion of sodium clouds originating in meteor deposition, but the authors cannot rule out the possibility of an ion conversion mechanism.

  13. Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma.

    PubMed

    Kruizinga, Roeliene C; van Marion, Denise M S; den Dunnen, Wilfred F A; de Groot, Jan C; Hoving, Eelco W; Oosting, Sjoukje F; Timmer-Bosscha, Hetty; Derks, Rosalie P H; Cornelissen, Chantal; van der Luijt, Rob B; Links, Thera P; de Vries, Elisabeth G E; Walenkamp, Annemiek M E

    2016-10-01

    Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel-Lindau (VHL) disease due to a VHL germline mutation. This mutation leads to enhanced transcription of chemokine receptor 4 (CXCR4), its ligand (CXCL12) and vascular endothelial growth factor A (VEGFA). We aimed to determine in VHL-related and sporadic hemangioblastomas CXCR4, CXCL12, and VEGFA protein expression and to correlate this to hemangioblastoma size and expression in normal surrounding tissue. 27 patients with a hemangioblastoma were included for analysis of immunohistochemistry of tissue, MRI and DNA. Hemangioblastomas overexpress CXCR4, CXCL12, and VEGFA compared to normal surrounding tissue. In sporadic hemangioblastomas the mean percentage of CXCR4 positive hemangioblastoma cells was 16 %, SD 8.4, in VHL-related hemangioblastomas 8 %, SD 4.4 (P = 0.002). There was no relation between preoperative tumor size and CXCR4 or CXCL12 expression. Compared to normal surrounding tissue CXCR4, CXCL12, and VEGFA were overexpressed in hemangioblastomas. Most interestingly, sporadic hemangioblastomas overexpress CXCR4 compared to VHL-related hemangioblastoma.

  14. Neuronal intranuclear inclusions distinguish familial FTD-MND type from sporadic cases.

    PubMed

    Mackenzie, Ian R A; Feldman, Howard

    2004-01-01

    Ubiquitin-immunoreactive (ub-ir) neuronal cytoplasmic inclusions are characteristically found in the extramotor cortex in patients with motor neuron disease (MND) and dementia (MND-dementia) and in a subset of patients with frontotemporal dementia (FTD) without motor symptoms (FTD-MND type). Recently, ub-ir neuronal intranuclear inclusions have been described in a small number of patients with familial FTD-MND type. To better define the sensitivity and specificity of this pathological change, we examined postmortem tissue from 14 patients with FTD-MND type (8 familial, 6 sporadic), 10 cases of MND-dementia (5 familial, 5 sporadic) and 19 cases of MND with no history of cognitive dysfunction (2 familial, 17 sporadic). Numerous intranuclear inclusions were found in multiple anatomic sites in 6/8 cases of familial FTD-MND. Rare intranuclear inclusions were present in the hippocampal dentate granule cells in 1 case of familial MND-dementia. No sporadic cases had intranuclear inclusions. These findings suggest that intranuclear inclusions are specific for familial FTD and may identify a subset of families with a common genetic basis. Although intranuclear inclusions are most characteristic of families with pure FTD, they may also be found in some pedigrees with both FTD and MND, further supporting the hypothesis that FTD-MND type and MND-dementia represent a clinicopathological spectrum of disease.

  15. Novel and functional ATG12 gene variants in sporadic Parkinson's disease.

    PubMed

    Li, Yuequn; Huang, Jian; Pang, Shuchao; Wang, Haihua; Zhang, Aimei; Hawley, Robert G; Yan, Bo

    2017-03-16

    Parkinson's disease (PD) is a common and progressive neurodegenerative disease, including familial and sporadic cases. To date, genetic causes for sporadic PD, majority of PD cases, remain largely unknown. Accumulating evidence indicates that dysfunctional autophagy, a highly conserved cellular process, is involved in the PD pathogenesis. We speculated that changed expression levels of autophagy-related genes (ATG) may contribute to PD development. Previously, we have genetically analyzed ATG5 and ATG7 genes in sporadic PD patients and identified several functional DNA sequence variants (DSVs). In groups of sporadic PD patients and ethic-matched healthy controls in this study, we further genetically and functionally analyzed the promoter of ATG12, a critical gene for autophagososme formation. The results showed that three DNA sequence variants (DSVs), g.115842507G>T,g.115842394C>T and g.115841817_18del, were identified three PD patients, which significantly altered transcriptional activity of ATG12 gene promoter, probably due to abolishing or creating binding sites for transcription factors. The transcriptional activity of ATG12 gene promoter was not significantly affected by other two DSVs identified in PD patients, g.115842640A>C and g.115842242G>C, which may not alter binding sites for transcription factors. Therefore, these three functional DSVs identified in PD patient may change ATG12 protein levels, contributing to PD development as a risk factor by interfering with autophagy as well as non-autophagy functions.

  16. Genetic Predisposition to Sporadic Congenital Hearing Loss in a Pediatric Population

    PubMed Central

    Jung, Jinsei; Lee, Joon Suk; Cho, Kyeong Jee; Yu, Seyoung; Yoon, Joo-Heon; Yung Gee, Heon; Choi, Jae Young

    2017-01-01

    Discriminating between inherited and non-inherited sporadic hearing loss is challenging. Here, we attempted to delineate genetic inheritance in simplex cases of severe-to-profound congenital hearing loss in Korean children. Variations in SLC26A4 and GJB2 in 28 children with bilateral severe-to-profound non-syndromic hearing loss (NSHL) without familial history were analyzed using Sanger sequencing. Genetic analysis of individuals without mutations in SLC26A4 and GJB2 was performed by whole exome sequencing (WES). Bi-allelic mutations in SLC26A4 and GJB2 were identified in 12 and 3 subjects, respectively. Of the 13 individuals without mutations in SLC26A4 and GJB2, 2 and 1 carried compound heterozygous mutations in MYO15A and CDH23, respectively. Thus, 64.3% (18/28) of individuals with NSHL were determined to be genetically predisposed. Individuals with sporadic severe-to-profound NSHL were found to mostly exhibit an autosomal recessive inheritance pattern. Novel causative candidate genes for NSHL were identified by analysis of WES data of 10 families without mutations in known causative genes. Bi-allelic mutations predisposing to NSHL were identified in 64.3% of subjects with sporadic severe-to-profound NSHL. Given that several causative genes for NSHL are still unidentified, genetic inheritance of sporadic congenital hearing loss could be more common than that indicated by our results. PMID:28383030

  17. S182 and STM2 gene missense mutations in sporadic alzheimer disease

    SciTech Connect

    Higuchi, Susumu; Matsushita, Sachio; Hasegawa, Yoshio; Muramatsu, Taro

    1996-07-26

    The linkage of genes S182 and STM2 to early-onset or late-onset sporadic Alzheimer disease (AD) was not found in a group of 97 clinically-diagnosed AD patients and 46 autopsy-confirmed AD cases, using PCR-RFLP methods. 7 refs.

  18. Sporadic Cerebral Cavernous Malformations: Report of Further Mutations of CCM Genes in 40 Italian Patients

    PubMed Central

    D'Angelo, Rosalia; Alafaci, Concetta; Scimone, Concetta; Ruggeri, Alessia; Salpietro, Francesco Maria; Bramanti, Placido; Tomasello, Francesco; Sidoti, Antonina

    2013-01-01

    Cerebral cavernous malformations (CCMs) are vascular lesions characterized by abnormally enlarged capillary cavities, affecting the central nervous system. CCMs can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1 (K-Rev interaction trapped 1 (KRIT1)), CCM2 (MGC4607), and CCM3 (PDCD10). CCMs occur as a single or multiple malformations that can lead to seizures, focal neurological deficits, hemorrhagic stroke, and headache. However, patients are frequently asymptomatic. In our previous mutation screening, performed in a cohort of 95 Italian patients, both sporadic and familial, we have identified several mutations in CCM genes, three of which in three distinct sporadic patients. In this study, representing further molecular screening of the three CCM genes, in a south Italian cohort of CCM patients enrolled by us in the last three years, we report the identification of other four new mutations in 40 sporadic patients with either single or multiple CCM. PMID:24058906

  19. Sporadic cerebral cavernous malformations: report of further mutations of CCM genes in 40 Italian patients.

    PubMed

    D'Angelo, Rosalia; Alafaci, Concetta; Scimone, Concetta; Ruggeri, Alessia; Salpietro, Francesco Maria; Bramanti, Placido; Tomasello, Francesco; Sidoti, Antonina

    2013-01-01

    Cerebral cavernous malformations (CCMs) are vascular lesions characterized by abnormally enlarged capillary cavities, affecting the central nervous system. CCMs can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1 (K-Rev interaction trapped 1 (KRIT1)), CCM2 (MGC4607), and CCM3 (PDCD10). CCMs occur as a single or multiple malformations that can lead to seizures, focal neurological deficits, hemorrhagic stroke, and headache. However, patients are frequently asymptomatic. In our previous mutation screening, performed in a cohort of 95 Italian patients, both sporadic and familial, we have identified several mutations in CCM genes, three of which in three distinct sporadic patients. In this study, representing further molecular screening of the three CCM genes, in a south Italian cohort of CCM patients enrolled by us in the last three years, we report the identification of other four new mutations in 40 sporadic patients with either single or multiple CCM.

  20. Cells transformed by murine herpesvirus 68 (MHV-68) release compounds with transforming and transformed phenotype suppressing activity resembling growth factors.

    PubMed

    Šupolíková, M; Staňová, A Vojs; Kúdelová, M; Marák, J; Zelník, V; Golais, F

    2015-12-01

    In this study, we investigated the medium of three cell lines transformed with murine herpesvirus 68 (MHV-68) in vitro and in vivo, 68/HDF, 68/NIH3T3, and S11E, for the presence of compounds resembling growth factors of some herpesviruses which have displayed transforming and transformed phenotype suppressing activity in normal and tumor cells. When any of spent medium was added to cell culture we observed the onset of transformed phenotype in baby hamster kidney cells (BHK-21) cells and transformed phenotype suppressing activity in tumor human epithelial cells (HeLa). In media tested, we have identified the presence of putative growth factor related to MHV-68 (MHGF-68). Its bivalent properties have been blocked entirely by antisera against MHV-68 and two monoclonal antibodies against glycoprotein B (gB) of MHV-68 suggesting viral origin of MHGF-68. The results of initial efforts to separate MHGF-68 on FPLC Sephadex G15 column in the absence of salts revealed the loss of its transforming activity but transformed phenotype suppressing activity retained. On the other hand, the use of methanol-water mobile phase on RP-HPLC C18 column allowed separation of MHGF-68 to two compounds. Both separated fractions, had only the transforming activity to normal cells. Further experiments exploring the nature and the structure of hitherto unknown MHGF-68 are now in the progress to characterize its molecular and biological properties.

  1. Structural changes upon peroxynitrite-mediated nitration of peroxiredoxin 2; nitrated Prx2 resembles its disulfide-oxidized form.

    PubMed

    Randall, Lía; Manta, Bruno; Nelson, Kimberly J; Santos, Javier; Poole, Leslie B; Denicola, Ana

    2016-01-15

    Peroxiredoxins are cys-based peroxidases that function in peroxide detoxification and H2O2-induced signaling. Human Prx2 is a typical 2-Cys Prx arranged as pentamers of head-to-tail homodimers. During the catalytic mechanism, the active-site cysteine (CP) cycles between reduced, sulfenic and disulfide state involving conformational as well as oligomeric changes. Several post-translational modifications were shown to affect Prx activity, in particular CP overoxidation which leads to inactivation. We have recently reported that nitration of Prx2, a post-translational modification on non-catalytic tyrosines, unexpectedly increases its peroxidase activity and resistance to overoxidation. To elucidate the cross-talk between this post-translational modification and the enzyme catalysis, we investigated the structural changes of Prx2 after nitration. Analytical ultracentrifugation, UV absorption, circular dichroism, steady-state and time-resolved fluorescence were used to connect catalytically relevant redox changes with tyrosine nitration. Our results show that the reduced nitrated Prx2 structurally resembles the disulfide-oxidized native form of the enzyme favoring a locally unfolded conformation that facilitates disulfide formation. These results provide structural basis for the kinetic analysis previously reported, the observed increase in activity and the resistance to overoxidation of the peroxynitrite-treated enzyme.

  2. MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme.

    PubMed

    Lin, J; Teo, S; Lam, D H; Jeyaseelan, K; Wang, S

    2012-10-04

    Glioblastoma multiforme (GBM) is a heterogeneous disease despite its seemingly uniform pathology. Deconvolution of The Cancer Genome Atlas's GBM gene expression data has unveiled the existence of distinct gene expression signature underlying discrete GBM subtypes. Recent conflicting findings proposed that microRNA (miRNA)-10b exclusively regulates glioma growth or invasion but not both. We showed that silencing of miRNA-10b by baculoviral decoy vectors in a glioma cell line resembling the mesenchymal subtype of GBM reduces its growth, invasion and angiogenesis while promoting apoptosis in vitro. In an orthotopic human glioma mouse model, inhibition of miRNA-10b diminishes the invasiveness, angiogenicity and growth of the mesenchymal subtype-like glioma cells in the brain and significantly prolonged survival of glioma-bearing mice. We demonstrated that the pleiotropic nature of miRNA-10b was due to its suppression of multiple tumor suppressors, including TP53, FOXO3, CYLD, PAX6, PTCH1, HOXD10 and NOTCH1. In particular, siRNA-mediated knockdown experiments identified TP53, PAX6, NOTCH1 and HOXD10 as invasion regulatory genes in our mesenchymal subtype-like glioma cells. By interrogating the REMBRANDT, we noted that dysregulation of many direct targets of miRNA-10b was associated with significantly poorer patient survival. Thus, our study uncovers a novel role for miRNA-10b in regulating angiogenesis and suggests that miRNA-10b may be a pleiotropic regulator of gliomagenesis.

  3. TGFbeta and miRNA regulation in familial and sporadic breast cancer.

    PubMed

    Danza, Katia; De Summa, Simona; Pinto, Rosamaria; Pilato, Brunella; Palumbo, Orazio; Carella, Massimo; Popescu, Ondina; Digennaro, Maria; Lacalamita, Rosanna; Tommasi, Stefania

    2017-01-30

    The term 'BRCAness' was introduced to identify sporadic malignant tumors sharing characteristics similar to those germline BRCA-related. Among all mechanisms attributable to BRCA1 expression silencing, a major role has been assigned to microRNAs. MicroRNAs role in familial and sporadic breast cancer has been explored but few data are available about microRNAs involvement in homologous recombination repair control in these breast cancer subgroups. Our aim was to seek microRNAs associated to pathways underlying DNA repair dysfunction in breast cancer according to a family history of the disease. Affymetrix GeneChip microRNA Arrays were used to perform microRNA expression analysis in familial and sporadic breast cancer. Pathway enrichment analysis and microRNA target prediction was carried out using DIANA miRPath v.3 web-based computational tool and miRWalk v.2 database. We analyzed an external gene expression dataset (E-GEOD-49481), including both familial and sporadic breast cancers. For microRNA validation, an independent set of 19 familial and 10 sporadic breast cancers was used. Microarray analysis identified a signature of 28 deregulated miRNAs. For our validation analyses by real time PCR, we focused on miR-92a-1*, miR-1184 and miR-943 because associated to TGF-β signalling pathway, ATM and BRCA1 genes expression. Our results highlighted alterations in miR-92a-1*, miR-1184 and miR-943 expression levels suggesting their involvement in repair of DNA double-strand breaks through TGF-beta pathway control.

  4. Mutation analysis of the RET gene in individuals with sporadic and familial pheochromocytoma

    SciTech Connect

    Iyengar, S.; Sirugo, G.; Bale, A.E.

    1994-09-01

    Pheochromocytoma is common to many familial cancer syndromes including multiple endocrine neoplasia type 2A (MEN2A), von Hippel-Lindau (VHL) and neurofibromatosis (NF). Although sporadic cases of pheochromocytoma have been examined for mutations in exons 10, 11 and 16 of the RET gene, only one case with a mutation in exon 16 has been reported thus far. We are performing systematic examination of exons of the RET gene, which has previously been associated with mutation in both MEN2 A and B, to determine the role RET may play in the etiology of pheochromocytoma. Seventeen cases of sporadic pheochromocytoma and 3 cases of sporadic medullary thyroid carcinoma were obtained from the pathology archives. Histopathology of all specimens was confirmed to be either pheochromocytoma or medullary thyroid carcinoma before DNA was extracted from 0.5{mu} thin sections of paraffin-embedded tissue. DNA from familial pheochromocytoma patients was also available for analysis. All sporadic and familial cases were amplified for exons 2, 6 and 16 of the RET gene. Single strand conformational polymorphism (SSCP) analysis was performed for exons 2 and 6. On finding a variation in the SSCP pattern in the pheochromocytoma kindred we sequenced all the samples for exon 2. A single base pair variation was found, which did not segregate with pheochromocytoma in the family. No variant SSCP patterns have been observed with the exon 6 PCR products thus far. Exon 16 PCR products were subjected to DNA restriction analysis with Fok I. This enzyme detects a single base pair change associated with MEN2 B. With the exception of one sample with sporadic medullary thyroid carcinoma, all samples showed the normal pattern on DNA restriction analysis. Thus we can exclude exons 2 and 6 of the RET gene in the pathogenesis of pheochromocytoma. SSCP analyses with other exons in the RET gene are underway.

  5. Cholesterol, endocrine and metabolic disturbances in sporadic anovulatory women with regular menstruation

    PubMed Central

    Mumford, Sunni L.; Schisterman, Enrique F.; Siega-Riz, Anna Maria; Gaskins, Audrey J.; Steiner, Anne Z.; Daniels, Julie L.; Olshan, Andrew F.; Hediger, Mary L.; Hovey, Kathleen; Wactawski-Wende, Jean; Trevisan, Maurizio; Bloom, Michael S.

    2011-01-01

    BACKGROUND Sporadic anovulation among regularly menstruating women is not well understood. It is hypothesized that cholesterol abnormalities may lead to hormone imbalances and incident anovulation. The objective was to evaluate the association between lipoprotein cholesterol levels and endocrine and metabolic disturbances and incident anovulation among ovulatory and anovulatory women reporting regular menstruation. METHODS The BioCycle Study was a prospective cohort study conducted at the University at Buffalo from September 2005 to 2007, which followed 259 self-reported regularly menstruating women aged 18–44 years, for one or two complete menstrual cycles. Sporadic anovulation was assessed across two menstrual cycles. RESULTS Mean total and low-density lipoprotein cholesterol and triglycerides levels across the menstrual cycles were higher during anovulatory cycles (mean difference: 4.6 (P = 0.01), 3.0 (P = 0.06) and 6.4 (P = 0.0002) mg/dl, respectively, adjusted for age and BMI). When multiple total cholesterol (TC) measures prior to expected ovulation were considered, we observed a slight increased risk of anovulation associated with increased levels of TC (odds ratio per 5 mg/dl increase, 1.07; 95% confidence interval, 0.99, 1.16). Sporadic anovulation was associated with an increased LH:FSH ratio (P = 0.002), current acne (P = 0.02) and decreased sex hormone-binding globulin levels (P = 0.005). CONCLUSIONS These results do not support a strong association between lipoprotein cholesterol levels and sporadic anovulation. However, sporadic anovulation among regularly menstruating women is associated with endocrine disturbances which are typically observed in women with polycystic ovary syndrome. PMID:21115506

  6. Fibroblast Biomarkers of Sporadic Parkinson's Disease and LRRK2 Kinase Inhibition.

    PubMed

    Smith, G A; Jansson, J; Rocha, E M; Osborn, T; Hallett, P J; Isacson, O

    2016-10-01

    It has been uncertain whether specific disease-relevant biomarker phenotypes can be found using sporadic Parkinson's disease (PD) patient-derived samples, as it has been proposed that there may be a plethora of underlying causes and pathological mechanisms. Fibroblasts derived from familial PD patients harboring leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), and Parkin mutations show clear disease-relevant mitochondrial phenotypes, which are exacerbated under conditions of pharmacological stress. We utilized fibroblasts derived from non-familial sporadic PD patients (without LRRK2 mutations) or LRRK2 mutation carriers to directly compare the cellular phenotypes during and after mitochondrial stress. We then determined the effects of pharmacological LRRK2 kinase inhibition using LRRK2-in-1. We found that there were two distinct populations of sporadic PD patient-derived fibroblast lines. One group of sporadic PD lines was highly susceptible to valinomycin-induced mitochondrial depolarization, emulating the mutant LRRK2 phenotype. These lines showed elevated mitochondrial superoxide/ nitric oxide levels, displayed increased mitochondrial and lysosome co-localization, and an increased rate of mitochondrial collapse, which corresponded with changes in mitochondrial fission and fusion proteins. The application of LRRK2-in-1 reversed decreased levels of mitochondrial and lysosome co-localization and partially restored mitochondrial network associated proteins and the mitochondrial membrane potential in the fibroblasts. This study identifies novel mitochondrial biomarkers in sporadic PD patient-derived fibroblast lines, which could be used as preclinical tools in which to test novel and known neuroprotective compounds.

  7. Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas

    SciTech Connect

    Deprez, R.H.L.; Groen, N.A.; Zwarthoff, E.C.; Hagemeijer, A.; Van Drunen, E.; Bootsma, D.; Koper, J.W.; Avezaat, C.J.J. ); Bianchi, A.B.; Seizinger, B.R. )

    1994-06-01

    The gene for the hereditary disorder neurofibromatosis type 2 (NF2), which predisposes for benign CNS tumors such as vestibular schwannomas and meningiomas, has been assigned to chromosome 22 and recently has been isolated. Mutations in the NF2 gene were found in both sporadic meningiomas and vestibular schwannomas. However, so far only 6 of the 16 exons of the gene have been analyzed. In order to extend the analysis of an involvement of the NF2 gene in the sporadic counterparts of these NF2-related tumors, the authors have used reverse transcriptase-PCR amplification followed by SSCP and DNA sequence analysis to screen for mutations in the coding region of the NF2 gene. Analysis of the NF2 gene transcript in 53 unrelated patients with meningiomas and vestibular schwannomas revealed mutations in 32% of the sporadic meningiomas (n = 44), in 50% of the sporadic vestibular schwannomas (n = 4), in 100% of the tumors found in NF2 patients (n = 2), and in one of three tumors from multiple-meningioma patients. Of the 18 tumors in which a mutation in the NF2 gene transcript was observed and the copy number of chromosome 22 could be established, 14 also showed loss of (parts of) chromosome 22. This suggests that in sporadic meningiomas and NF2-associated tumors the NF2 gene functions as a recessive tumor-suppressor gene. The mutations detected resulted mostly in frameshifts, predicting truncations starting within the N-terminal half of the putative protein. 23 refs., 2 figs. 3 tabs.

  8. The heat-pipe resembling action of boiling bubbles in endovenous laser ablation.

    PubMed

    van der Geld, Cees W M; van den Bos, Renate R; van Ruijven, Peter W M; Nijsten, Tamar; Neumann, H A Martino; van Gemert, Martin J C

    2010-11-01

    Endovenous laser ablation (EVLA) produces boiling bubbles emerging from pores within the hot fiber tip and traveling over a distal length of about 20 mm before condensing. This evaporation-condensation mechanism makes the vein act like a heat pipe, where very efficient heat transport maintains a constant temperature, the saturation temperature of 100 degrees C, over the volume where these non-condensing bubbles exist. During EVLA the above-mentioned observations indicate that a venous cylindrical volume with a length of about 20 mm is kept at 100 degrees C. Pullback velocities of a few mm/s then cause at least the upper part of the treated vein wall to remain close to 100 degrees C for a time sufficient to cause irreversible injury. In conclusion, we propose that the mechanism of action of boiling bubbles during EVLA is an efficient heat-pipe resembling way of heating of the vein wall.

  9. Westermarck, Freud, and the incest taboo: does familial resemblance activate sexual attraction?

    PubMed

    Fraley, R Chris; Marks, Michael J

    2010-09-01

    Evolutionary psychological theories assume that sexual aversions toward kin are triggered by a nonconscious mechanism that estimates the genetic relatedness between self and other. This article presents an alternative perspective that assumes that incest avoidance arises from consciously acknowledged taboos and that when awareness of the relationship between self and other is bypassed, people find individuals who resemble their kin more sexually appealing. Three experiments demonstrate that people find others more sexually attractive if they have just been subliminally exposed to an image of their opposite-sex parent (Experiment 1) or if the face being rated is a composite image based on the self (Experiment 2). This finding is reversed when people are aware of the implied genetic relationship (Experiment 3). These findings have implications for a century-old debate between E. Westermarck and S. Freud, as well as contemporary research on evolution, mate choice, and sexual imprinting.

  10. Discovery of crystalline inclusions in Bacillus licheniformis that resemble parasporal crystals of Bacillus thuringiensis.

    PubMed

    Yan, Ming; Roehrl, Michael H; Wang, Julia Y

    2007-09-01

    Crystalline inclusions were discovered in stationary and sporulating cells of the spore-forming bacterium Bacillus licheniformis ATCC 9945a. As detected by electron microscopy, dying or sporulating bacterial cells contain a single crystal of strikingly large size. The crystals in sporulating cells are located next to nascent spores and can be several times larger than the spores. Morphologically, most crystals are rhomboid with uniformly spaced grids. These newly discovered crystalline inclusions of B. licheniformis closely resemble parasporal crystals of Bacillus thuringiensis that are formed by insecticidal toxin proteins and used widely as biopesticides. The taxonomic identity of this strain was verified by its 16S rRNA gene sequence and its fatty acid profile. The finding of crystal proteins in B. licheniformis may lead to the discovery of new protein toxins and may expand our pool of biopesticides.

  11. Acral Peeling Skin Syndrome Resembling Epidermolysis Bullosa Simplex in a 10-Month-Old Boy

    PubMed Central

    Kavaklieva, S.; Yordanova, I.; Bruckner-Tuderman, L.; Has, C.

    2013-01-01

    The acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder clinically characterized by asymptomatic desquamation of the skin limited to the hands and feet and histologically by cleavage at the stratum granulosum and stratum corneum level [Kiritsi et al.: J Invest Dermatol 2010;130:1741–1746]. We report on a 10-month-old boy with a history of skin peeling limited to the hands and feet since 2 months of age. Clinical examination revealed erythematous erosions with peripheral desquamation and flaccid blisters. DNA mutation analysis detected two heterozygous TGM5 mutations: c.2T>C, p.M1T in exon 1 and c.337G>T, p.G113C in exon 3 in keeping with the diagnosis of APSS. The clinical presentation of APSS alone might be confusing and strongly resemble epidermolysis bullosa simplex making the differential diagnosis difficult. PMID:24019772

  12. Frontal lobe epilepsy with atypical seizure semiology resembling shuddering attacks or wet dog shake seizures.

    PubMed

    Jahodova, Alena; Krsek, Pavel; Komarek, Vladimir; Kudr, Martin; Kyncl, Martin; Zamecnik, Josef; Tichy, Michal

    2012-03-01

    We report a girl with a drug-resistant frontal lobe epilepsy caused by focal cortical dysplasia, who exhibited uncommon seizures. The seizures consisted of shoulder or whole body shuddering after a short psychic aura and face grimacing. Consciousness was fully preserved. The seizures resembled "wet dog shake" seizures described in rat models of epilepsy or shuddering attacks in infants. EEG findings were inconclusive, however, MRI showed a clear dysplastic lesion in the right frontal mesial and polar structures. The patient underwent an extended lesionectomy guided by neuronavigation and intraoperative electrocorticography. Focal cortical dysplasia type Ib was histologically confirmed and the patient has been seizure-free for the three years following resection. [Published with video sequences].

  13. Silica deposits on Mars with features resembling hot spring biosignatures at El Tatio in Chile

    NASA Astrophysics Data System (ADS)

    Ruff, Steven W.; Farmer, Jack D.

    2016-11-01

    The Mars rover Spirit encountered outcrops and regolith composed of opaline silica (amorphous SiO2.nH2O) in an ancient volcanic hydrothermal setting in Gusev crater. An origin via either fumarole-related acid-sulfate leaching or precipitation from hot spring fluids was suggested previously. However, the potential significance of the characteristic nodular and mm-scale digitate opaline silica structures was not recognized. Here we report remarkably similar features within active hot spring/geyser discharge channels at El Tatio in northern Chile, where halite-encrusted silica yields infrared spectra that are the best match yet to spectra from Spirit. Furthermore, we show that the nodular and digitate silica structures at El Tatio that most closely resemble those on Mars include complex sedimentary structures produced by a combination of biotic and abiotic processes. Although fully abiotic processes are not ruled out for the Martian silica structures, they satisfy an a priori definition of potential biosignatures.

  14. Congenital biliary tract malformation resembling biliary cystadenoma in a captive juvenile African lion (Panthera leo).

    PubMed

    Caliendo, Valentina; Bull, Andrew C J; Stidworthy, Mark F

    2012-12-01

    A captive 3-mo-old white African lion (Panthera leo) presented with clinical signs of acute pain and a distended abdomen. Despite emergency treatment, the lion died a few hours after presentation. Postmortem examination revealed gross changes in the liver, spleen, and lungs and an anomalous cystic structure in the bile duct. Histologic examination identified severe generalized multifocal to coalescent necrotizing and neutrophilic hepatitis, neutrophilic splenitis, and mild interstitial pneumonia, consistent with bacterial septicemia. The abnormal biliary structures resembled biliary cystadenoma. However, due to the age of the animal, they were presumed to be congenital in origin. Biliary tract anomalies and cystadenomas have been reported previously in adult lions, and this case suggests that at least some of these examples may have a congenital basis. It is unclear whether the lesion was an underlying factor in the development of hepatitis.

  15. The Effect of Perceived Parent–Child Facial Resemblance on Parents’ Trait Anxiety: The Moderating Effect of Parents’ Gender

    PubMed Central

    Yu, Quanlei; Zhang, Qiuying; Chen, Jianwen; Jin, Shenghua; Qiao, Yuanyuan; Cai, Weiting

    2016-01-01

    Father–child facial resemblance is an important cue for men to evaluate paternity. Previous studies found that fathers’ perceptions of low facial resemblance with offspring lead to low confidence of paternity. Fathers’ uncertainty of paternity could cause psychological stress and anxiety, which, after a long time, may further turn into trait anxiety. Conversely, females can ensure a biological connection with offspring because of internal fertilization. The purpose of this study was thus to examine the role of parents’ gender in the effect of parents’ perceived facial resemblance with child on their trait anxiety. In this study, 151 parents (father or mother) from one-child families reported their facial resemblance with child and their trait anxiety. Results showed that (i) males tended to perceive higher facial similarity with child than did females and (ii) males’ perceived facial resemblance with child significantly predicted trait anxiety, whereas females’ perceived facial resemblance did not. These findings suggested that the uncertainty of paternity contributed to the trait anxiety of fathers, but not mothers. PMID:27199876

  16. Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis

    PubMed Central

    Lederer, Carsten W; Torrisi, Antonietta; Pantelidou, Maria; Santama, Niovi; Cavallaro, Sebastiano

    2007-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a fatal disorder caused by the progressive degeneration of motoneurons in brain and spinal cord. Despite identification of disease-linked mutations, the diversity of processes involved and the ambiguity of their relative importance in ALS pathogenesis still represent a major impediment to disease models as a basis for effective therapies. Moreover, the human motor cortex, although critical to ALS pathology and physiologically altered in most forms of the disease, has not been screened systematically for therapeutic targets. Results By whole-genome expression profiling and stringent significance tests we identify genes and gene groups de-regulated in the motor cortex of patients with sporadic ALS, and interpret the role of individual candidate genes in a framework of differentially expressed pathways. Our findings emphasize the importance of defense responses and cytoskeletal, mitochondrial and proteasomal dysfunction, reflect reduced neuronal maintenance and vesicle trafficking, and implicate impaired ion homeostasis and glycolysis in ALS pathogenesis. Additionally, we compared our dataset with publicly available data for the SALS spinal cord, and show a high correlation of changes linked to the diseased state in the SALS motor cortex. In an analogous comparison with data for the Alzheimer's disease hippocampus we demonstrate a low correlation of global changes and a moderate correlation for changes specifically linked to the SALS diseased state. Conclusion Gene and sample numbers investigated allow pathway- and gene-based analyses by established error-correction methods, drawing a molecular portrait of the ALS motor cortex that faithfully represents many known disease features and uncovers several novel aspects of ALS pathology. Contrary to expectations for a tissue under oxidative stress, nuclear-encoded mitochondrial genes are uniformly down-regulated. Moreover, the down-regulation of mitochondrial and glycolytic

  17. Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis

    PubMed Central

    Chen, YongPing; Wei, QianQian; Chen, XuePing; Li, ChunYu; Cao, Bei; Ou, RuWei; Hadano, Shinji; Shang, Hui-Fang

    2016-01-01

    Background: Accumulating evidence indicates that miRNAs play an important role in the development of amyotrophic lateral sclerosis (ALS). Most of previous studies on miRNA dysregulation in ALS focused on the alterative expression in ALS animal model or in limited samples from European patients with ALS. In the present study, the miRNA expression profiles were investigated in Chinese ALS patients to explore leukocytes miRNAs as a potential biomarker for the diagnosis of ALS. Methods: We analyzed the expression profiles of 1733 human mature miRNAs using microarray technology in leukocytes obtained from 5 patients with sporadic ALS (SALS) and 5 healthy controls. An independent group of 83 SALS patients, 24 Parkinson's disease (PD) patients and 61 controls was used for validation by real-time polymerase chain reaction assay. Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. In addition, target genes and signaling information of validated differential expression miRNAs were predicted using Bioinformatics. Results: Eleven miRNAs, including four over-expressed and seven under-expressed miRNAs detected in SALS patients compared to healthy controls were selected for validation. Four under-expressed microRNAs, including hsa-miR-183, hsa-miR-193b, hsa-miR-451, and hsa-miR-3935, were confirmed in validation stage by comparison of 83 SALS patients and 61 HCs. Moreover, we identified a miRNA panel (hsa-miR-183, hsa-miR-193b, hsa-miR-451, and hsa-miR-3935) having a high diagnostic accuracy of SALS (AUC 0.857 for the validation group). However, only hsa-miR-183 was significantly lower in SALS patients than that in PD patients and in HCs, while no differences were found between PD patients and HCs. By bioinformatics analysis, we obtained a large number of target genes and signaling information that are linked to neurodegeneration. Conclusion: This study provided evidence of abnormal miRNA expression patterns in the peripheral

  18. Can the TLR-4-Mediated Signaling Pathway Be “A Key Inflammatory Promoter for Sporadic TAA”?

    PubMed Central

    Ruvolo, Giovanni; Pisano, Calogera; Candore, Giuseppina; Lio, Domenico; Palmeri, Cesira; Maresi, Emiliano; Balistreri, Carmela R.

    2014-01-01

    Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR = 14.4, P = 0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments. PMID:25120286

  19. Case study of simultaneous observations of sporadic sodium layer, E-region field-aligned irregularities and sporadic E layer at low latitude of China

    NASA Astrophysics Data System (ADS)

    Xie, H. Y.; Ning, B. Q.; Zhao, X. K.; Hu, L. H.

    2017-03-01

    Using the Na lidar at Haikou (20.0°N, 110.3°E), the VHF coherent radar and the digital ionosonde both at Sanya (18.4°N, 109.6°E), cases of simultaneous observations of sporadic sodium layer (SSL), E-region field-aligned irregularities (FAI) and sporadic E layer (Es) in the mesosphere and lower thermosphere (MLT) region at low latitude of China are studied. It is found that SSL occurs simultaneously or follows the enhancement of Es and FAI. The Es, FAI and SSL descend slowly with time which is mostly controlled by the diurnal tide (DT). Besides, the interaction of gravity wave (GW) with tides can cause oscillations in FAI and SSL. Our observations support the neutralization of ions for SSL formation: when the metallic ions layer descents to the altitudes where models predict, the sodium ions convert rapidly to atomic Na that may form an SSL event. Moreover, the SSL peak density will increase (decrease) in the convergence (divergence) vertical shear region of zonal wind.

  20. Model Simulation of Ionosphere Electron Density with Dynamic Transportation and Mechanism of Sporadic E Layers in Lower Part of Ionosphere

    NASA Astrophysics Data System (ADS)

    Lin, Y. C.; Chu, Y. H.

    2015-12-01

    There are many physical theories responsible for explanation the generation mechanism of sporadic E (Es) plasma irregularities. In middle latitude, it's generally believed that sporadic E layers occur in vertical ion convergent areas driven by horizontal neutral wind shear. The sporadic E layers appear characteristic of abundant metallic ion species (i.e., Fe+, Mg+, Na+), that lifetime are longer than molecular ions by a factor of several orders, have been demonstrated by rocket-borne mass spectrometric measurements. On the basic of the GPS Radio Occultation (RO), using the scintillations of the GPS signal-to-noise ratio and intense fluctuation of excess phase, the global and seasonal sporadic E layers occurrence rates could be retrieved. In our previous study we found there is averaged 10 kilometers shift in height between the COSMIC-retrieved sporadic E layer occurrence rate and the sporadic E occurrence rate modeled from considering the convergence/divergence of Fe+ vertical flux. There are many reasons that maybe result in the altitude differences, e.g., tidal wind with phase shift, electric field driven force, iron species distributions. In this research, the quantitative analyses for electric field drives Es layers translations in vertical direction are presented. The tidal wind driven sporadic E layers have been simulating by modeling several nonmetallic ions (O+(4S), O+(2D), O+(2p), N+, N2+, O2+, NO+) and metallic ions (Fe+, FeO2+, FeN2+, FeO+) with wind shear transportation. The simulation result shows the Fe+ particles accumulate at zonal wind shear convergent regions and form the thin sporadic E layers. With the electric field taking into account, the whole shape of sporadic E layers vertical shift 2~5 km that depending on what magnitude and direction of electric field is added.

  1. Three geese resembling Gray-Bellied Brant/Lawrence's Brant from Long Island, New York

    USGS Publications Warehouse

    Buckley, P.A.; Mitra, S.S.

    2002-01-01

    Three oddly plumaged brant, intermediate in several respects between 'Atlantic' or 'Pale-bellied Brant' (hrota) and ?Black Brant? (nigricans) were photographed and described on western Long Island, New York during 2002 (two in March, the third in October). Their plumage corresponded to that of the little-studied, and apparently genetically distinctive small population known among goose biologists as 'Gray-bellied Brant,' which breeds only on a few islands in the western Canadian High Arctic, stages in migration in the inner Aleutians, and winters in a small portion of the Greater Puget Sound area. But Gray-bellied Brant also wander, having recently been found in winter as far from Puget Sound as Baja California in the west, and Iceland and the British Isles to the east?these strays presumably having migrated southwest with Pacific-wintering nigricans and southeast with Atlantic-wintering hrota, respectively. Despite their tendency to associate with locally wintering hrota and nigricans, mixed pairs or hybrid young involving these vagrants have never been demonstrated in North America?nor have mixed pairs or hybrid young between hrota and nigricans, despite widespread belief to the contrary. Complicating the picture is that the type specimen of nigricans, a distinctive New Jersey specimen collected in 1846, also differs from 'true' Pacific Coast Black Brant in several respects, in a manner qualitatively similar to the LI birds described herein. The appearance of the type, often referred to informally as 'Lawrence?s Brant,' differs from typical Black Brant to such an extent that Delacour and Zimmer (1952) rejected application of nigricans to Pacific Black Brant, to which the name orientalis would have to be applied instead. Recent examination of museum specimens of breeding- and winter-area Gray-bellies confirms that Lawrence?s Brant closely resembles some of them?as do these three Long Island birds. Whatever the ultimate statuses of Gray-bellied and Lawrence's Brant

  2. Effect of facial self-resemblance on the startle response and subjective ratings of erotic stimuli in heterosexual men.

    PubMed

    Lass-Hennemann, Johanna; Deuter, Christian E; Kuehl, Linn K; Schulz, Andre; Blumenthal, Terry D; Schachinger, Hartmut

    2011-10-01

    Cues of kinship are predicted to increase prosocial behavior due to the benefits of inclusive fitness, but to decrease approach motivation due to the potential costs of inbreeding. Previous studies have shown that facial resemblance, a putative cue of kinship, increases prosocial behavior. However, the effects of facial resemblance on mating preferences are equivocal, with some studies finding that facial resemblance decreases sexual attractiveness ratings, while other studies show that individuals choose mates partly on the basis of similarity. To further investigate this issue, a psychophysiological measure of affective processing, the startle response, was used in this study, assuming that differences in approach motivation to erotic pictures will modulate startle. Male volunteers (n = 30) viewed 30 pictures of erotic female nudes while startle eyeblink responses were elicited by acoustic noise probes. The female nude pictures were digitally altered so that the face either resembled the male participant or another participant, or were not altered. Non-nude neutral pictures were also included. Importantly, the digital alteration was undetected by the participants. Erotic pictures were rated as being pleasant and clearly reduced startle eyeblink magnitude as compared to neutral pictures. Participants showed greater startle inhibition to self-resembling than to other-resembling or non-manipulated female nude pictures, but subjective pleasure and arousal ratings did not differ among the three erotic picture categories. Our data suggest that visual facial resemblance of opposite-sex nudes increases approach motivation in men, and that this effect was not due to their conscious evaluation of the erotic stimuli.

  3. Sporadic Multicentric Right Atrial and Right Ventricular Myxoma Presenting as Acute Pulmonary Thromboembolism.

    PubMed

    Singh, Satyajit; Tripathy, Mahendra Prasad; Mohanty, Bipin Bihari; Biswas, Sutapa

    2016-01-01

    Multicentric cardiac myxoma is a rare syndrome; usually it is familial. We report a rare case of sporadic right atrium (RA) and right ventricle (RV) myxoma in a 26-year-old female presenting to our hospital for the evaluation of sudden onset of dyspnea and left precordial pain attributed to the embolization of degenerating tumor fragments to the pulmonary artery (PA). The exact incidence of sporadic multicentric RA and RV myxoma presenting as acute pulmonary embolism is unknown as multicentric RA and RV myxoma are very rare. Myxomas presenting as pulmonary embolism is <10%. Majority of cardiac myxomas present as exertional dyspnea, chest pain, positional syncope, fever, weight loss and other constitutional symptoms. Any young patient presenting with acute onset dyspnea with multiple cardiac masses may have tumor embolization to the PA diagnosis with transthoracic echocardiography and high-resolution computed tomography of thorax, fast-tracks patient transfer for urgent cardiac surgery to prevent further embolization.

  4. CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients.

    PubMed

    Chiò, Adriano; Mora, Gabriele; Sabatelli, Mario; Caponnetto, Claudia; Traynor, Bryan J; Johnson, Janel O; Nalls, Mike A; Calvo, Andrea; Moglia, Cristina; Borghero, Giuseppe; Monsurrò, Maria Rosaria; La Bella, Vincenzo; Volanti, Paolo; Simone, Isabella; Salvi, Fabrizio; Logullo, Francesco O; Nilo, Riva; Battistini, Stefania; Mandrioli, Jessica; Tanel, Raffaella; Murru, Maria Rita; Mandich, Paola; Zollino, Marcella; Conforti, Francesca L; Brunetti, Maura; Barberis, Marco; Restagno, Gabriella; Penco, Silvana; Lunetta, Christian

    2015-04-01

    Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n = 64) and apparently sporadic ALS (n = 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHCHD10 mutations account for ∼ 1% of Italian ALS patients and are a cause of disease in subjects without dementia or other atypical clinical signs.

  5. Giant Sporadic Low Grade Malignant Peripheral Nerve Sheath (MPNST) of Left Thigh.

    PubMed

    Nikumbh, Dhiraj B; Suryawanshi, K H; Dravid, N V; Patil, T B; Rokade, C M

    2013-06-01

    Malignant Peripheral Nerve Sheath Tumours (MPNST) are rare spindle- cell sarcomas which are derived from the schwann cells or the pleuripotent cells of the neural crest. MPNSTs are usually located in the peripheral nerve trunk roots, extremities and in the head and neck region. These tumours may arise as sporadic variants or in patients with neurofibromatosis1 (NF1). The estimated incidence of MPNSTs in the patients with NF1is 2-5% as compared to a 0.001% incidence in the general population. Herein, we are reporting a case of a giant sporadic (NF1 independent) low grade MPNST of the left thigh in 65 year female patient, which had a good prognosis.

  6. Specificity of lectin-immobilized fluorescent nanospheres for colorectal tumors in a mouse model which more resembles the clinical disease

    PubMed Central

    Kitamura, Tokio; Sakuma, Shinji; Shimosato, Moe; Higashino, Haruki; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Hiwatari, Ken-ichiro; Kumagai, Hironori; Morimoto, Naoki; Koike, Seiji; Tobita, Etsuo; Hoffman, Robert M.; Gore, John C.; Pham, Wellington

    2014-01-01

    We are investigating an imaging agent that enables real-time and accurate diagnosis of early colorectal cancer at the intestinal mucosa by colonoscopy. The imaging agent is peanut agglutinin-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) chains encapsulating coumarin 6. Intracolonically-administered lectin-immobilized fluorescent nanospheres detect tumor-derived changes through molecular recognition of lectin for the terminal sugar of cancer-specific antigens on the mucosal surface. The focus of this study was to evaluate imaging abilities of the nanospheres in animal models that reflect clinical environments. We previously developed an orthotopic mouse model with human colorectal tumors growing on the mucosa of the descending colon to more resemble the clinical disease. The entire colon of the mice in the exposed abdomen was monitored in real-time with an in vivo imaging apparatus. Fluorescence from the nanospheres was observed along the entire descending colon after intracolonical administration of them from the anus. When the luminal side of the colon was washed with PBS, most of the nanospheres drained away. However, fluorescence persisted in areas where the cancer cells were implanted. Histological evaluation demonstrated that tumors were present in the mucosal epithelia where the nanospheres fluoresced. In contrast, no fluorescence was observed when control mice without tumors were tested. The lectin-immobilized fluorescent nanospheres were tumor specific and bound to tumors even after vigorously washing. The nanospheres non-specifically bound to normal mucosa were easily removed through mild washing. Results indicate that the nanospheres accompanied by colonoscopy will be a clinically-valuable diagnostic tool for the early stage primary colon carcinoma. PMID:24976331

  7. Disruption of the estrogen receptor β gene in mice causes myeloproliferative disease resembling chronic myeloid leukemia with lymphoid blast crisis

    PubMed Central

    Shim, Gil-Jin; Wang, Ling; Andersson, Sandra; Nagy, Noémi; Kis, Loránd Levente; Zhang, Qinghong; Mäkelä, Sari; Warner, Margaret; Gustafsson, Jan-Åke

    2003-01-01

    Proliferation of pluripotent, bone marrow stem cells, which develop to lymphoid and myeloid progenitors, is negatively regulated by estrogen. Although in estrogen deficiency and in estrogen receptor knockout mice there is significant alteration in bone marrow hematopoiesis, the effects of aging on estrogen receptor deficiencies in mice have not been investigated yet. In this study we show that by 1.5 years of age, estrogen receptor β knockout (ERβ–/–) mice develop pronounced splenomegaly that is much more severe in females than in males. Further characterization of these mice revealed myelogenous hyperplasia in bone marrow, an increase in the number of granulocytes and B lymphocytes in blood, lymphadenopathy, and infiltration of leukocytes in the liver and lung. Analysis by flow cytometry of the bone marrow cells revealed that the percentage and total number of Gr-1hi/Mac-1hi-positive granulocytes were increased by 15–30% and 100%, respectively. The numbers of B cells in the bone marrow and spleen were significantly higher in ERβ–/– mice than in WT littermates. Some of the ERβ–/– mice also had a severe lymphoproliferative phenotype. Thus the absence of ERβ results in a myeloproliferative disease resembling human chronic myeloid leukemia with lymphoid blast crisis. Our results indicate a previously unknown role for ERβ in regulating the differentiation of pluripotent hematopoietic progenitor cells and suggest that the ERβ–/– mouse is a potential model for myeloid and lymphoid leukemia. Furthermore, we suggest that ERβ agonists might have clinical value in the treatment of leukemia. PMID:12740446

  8. Rational protocols for testing faeces in the investigation of sporadic hospital-acquired diarrhoea.

    PubMed

    Gopal Rao, G; Ozerek, A E; Jeanes, A

    2001-02-01

    Many recent studies have demonstrated that routine examination of faeces for conventional enteric pathogens such as salmonella, shigella, campylobacter and parasites in patients who develop sporadic hospital-acquired diarrhoea is unnecessary and wasteful. In this paper the advantages and disadvantages of a restricted testing protocol in patients with hospital-acquired diarrhoea are reviewed. Practical issues for safe implementation of such a protocol are also discussed.

  9. Absence of RET proto-oncogene abnormalities in sporadic parathyroid tumors

    SciTech Connect

    Pausova, Z.; Janicic, N.; Konrad, E.

    1994-09-01

    Parathyroid tumors can occur either sporadically or as a part of inherited cancer syndromes such as multiple endocrine neoplasia (MEN) type 2A. Recently, development of this syndrome has been shown to be related to specific mutations in the RET proto-oncogene, a putative receptor tyrosine kinase. Activation of this proto-oncogene has been demonstrated not only in tumors of the MEN 2A syndrome, but also in other neoplasia of neuroectoderm origin, namely papillary thyroid carcinoma where a rearrangement of the RET proto-oncogene has been found. In the present study, a role of the RET proto-oncogene in the development of sporadic parathyroid tumors was investigated by analyzing DNA samples obtained from 13 parathyroid adenomas and 6 parathyroid hyperplasias. Southern blot, using BamHI restricted DNA, did not reveal any gross alteration of the gene. Polymerase chain reaction (PCR) was then employed to amplify DNA fragments corresponding to exons 10 and 11 in which all MEN 2A mutations have been identified. Amplified DNA fragments were all of expected size (exon 10, 182 bp; exon 11, 233 bp). Since a single point mutation at codon 634 has been found to be associated in close to 90% of cases with development of parathyroid tumors in patients with the MEN 2A syndrome, exon 11, containing this codon, was further examined by direct sequence analysis. Sequences obtained from all tumors tested, however, did not differ from the wild type sequence. Therefore, the mutation of the RET proto-oncogene commonly associated with parathyroid neoplasias in MEN 2A is uncommon in sporadic parathyroid tumors. This suggests that the pathogenesis of parathyroid tumors occurring sporadically may be different from those occurring in patients with the MEN 2A syndrome.

  10. Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus

    PubMed Central

    Zhao, Hui; Huang, Xiu-Feng; Zheng, Zhi-Li; Deng, Wen-Li; Lei, Xin-Lan; Xing, Dong-Jun; Ye, Liang; Xu, Su-Zhong; Chen, Jie; Zhang, Fang; Yu, Xin-Ping; Jin, Zi-Bing

    2016-01-01

    Objectives Infantile nystagmus (IN) is a genetically heterogeneous condition characterised by involuntary rhythmic oscillations of the eyes accompanied by different degrees of vision impairment. Two genes have been identified as mainly causing IN: FRMD7 and GPR143. The aim of our study was to identify the genetic basis of both sporadic IN and X-linked IN. Design Prospective analysis. Patients Twenty Chinese patients, including 15 sporadic IN cases and 5 from X-linked IN families, were recruited and underwent molecular genetic analysis. We first performed PCR-based DNA sequencing of the entire coding region and the splice junctions of the FRMD7 and GPR143 genes in participants. Mutational analysis and co-segregation confirmation were then performed. Setting All clinical examinations and genetic experiments were performed in the Eye Hospital of Wenzhou Medical University. Results Two mutations in the FRMD7 gene, including one novel nonsense mutation (c.1090C>T, p.Q364X) and one reported missense mutation (c.781C>G, p.R261G), were identified in two of the five (40%) X-linked IN families. However, none of putative mutations were identified in FRMD7 or GPR143 in any of the sporadic cases. Conclusions The results suggest that mutations in FRMD7 appeared to be the major genetic cause of X-linked IN, but not of sporadic IN. Our findings provide further insights into FRMD7 mutations, which could be helpful for future genetic diagnosis and genetic counselling of Chinese patients with nystagmus. PMID:27036142

  11. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    SciTech Connect

    Lucotte, G.; David, F.; Berriche, S.

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  12. Post-and prenatal testing for FSHD: Diagnostic approach for sporadic and familial cases

    SciTech Connect

    Bakker, E.; Wielen, M.J.R. van der; Losekoot, M.

    1994-09-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder. A major locus for FSHD was localized at the distal part of chromosome 4q. More recently, a disease associated DNA rearrangement was detected with the polymorphic probe p13E-11 (D4F104S1). In most FSHD patients, a shortened (< 28 kb instead of 50-300 kb) allele was detected. In sporadic patients a de novo deletion was found to be associated with the occurrence of FSHD. Diagnostically there were a number of problems to overcome. (1) About 5% of families show no linkage to chromosome 4q35. (2) Some 10% normal individuals show a shortened p13E11 allele, which is located at chromosome 10q. Our diagnostic strategy is as follows: If in sporadic patients a shortened p13E-11 allele is detected and neither parent shows this allele, then a de novo deletion has occurred and FSHD is proven. If no shortened allele is detected FSHD is less likely. In case one of the parents shows a shortened allele then clinical investigations and linkage studies are performed for both chromosome 4 and 10 markers. In familial cases both p13E-11 and polymorphic markers are tested. A shortened p13E-11 allele and/or chromosome 4 haplotype segregating with FSHD can be used for presymptomatic and prenatal diagnosis. Up to now, 45 sporadic cases and 21 families were referred for diagnosis. In 22 sporadic cases a shortened allele was detected, 13 were proven de novo. The first prenatal test was recently performed. The index patient was a de novo case with a shortened allele; the fetus had inherited this allele.

  13. Microvascular Pathology and Morphometrics of Sporadic and Hereditary Small Vessel Diseases of the Brain

    PubMed Central

    Craggs, Lucinda JL; Yamamoto, Yumi; Deramecourt, Vincent; Kalaria, Raj N

    2014-01-01

    Small vessel diseases (SVDs) of the brain are likely to become increasingly common in tandem with the rise in the aging population. In recent years, neuroimaging and pathological studies have informed on the pathogenesis of sporadic SVD and several single gene (monogenic) disorders predisposing to subcortical strokes and diffuse white matter disease. However, one of the limitations toward studying SVD lies in the lack of consistent assessment criteria and lesion burden for both clinical and pathological measures. Arteriolosclerosis and diffuse white matter changes are the hallmark features of both sporadic and hereditary SVDs. The pathogenesis of the arteriopathy is the key to understanding the differential progression of disease in various SVDs. Remarkably, quantification of microvascular abnormalities in sporadic and hereditary SVDs has shown that qualitatively the processes involved in arteriolar degeneration are largely similar in sporadic SVD compared with hereditary disorders such as cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Important significant regional differences in lesion location within the brain may enable one to distinguish SVDs, where frontal lobe involvement appears consistently with almost every SVD, but others bear specific pathologies in other lobes, such as the temporal pole in CADASIL and the pons in pontine autosomal dominant microangiopathy and leukoencephalopathy or PADMAL. Additionally, degenerative changes in the vascular smooth muscle cells, the cerebral endothelium and the basal lamina are often rapid and more aggressive in genetic disorders. Further quantification of other microvascular elements and even neuronal cells is needed to fully characterize SVD pathogenesis and to differentiate the usefulness of vascular interventions and treatments on the resulting pathology. PMID:25323665

  14. Ion Layer Separation and Equilibrium Zonal Winds in Midlatitude Sporadic E

    NASA Technical Reports Server (NTRS)

    Earle, G. D.; Kane, T. J.; Pfaff, R. F.; Bounds, S. R.

    2000-01-01

    In-situ observations of a moderately strong mid-latitude sporadic-E layer show a separation in altitude between distinct sublayers composed of Fe(+), Mg(+), and NO(+). From these observations it is possible to estimate the zonal wind field consistent with diffusive equilibrium near the altitude of the layer. The amplitude of the zonal wind necessary to sustain the layer against diffusive effects is less than 10 meters per second, and the vertical wavelength is less than 10 km.

  15. Significance of the Fanconi anemia FANCD2 protein in sporadic and metastatic human breast cancer.

    PubMed

    Rudland, Philip S; Platt-Higgins, Angela M; Davies, Lowri M; de Silva Rudland, Suzete; Wilson, James B; Aladwani, Abdulaziz; Winstanley, John H R; Barraclough, Dong L; Barraclough, Roger; West, Christopher R; Jones, Nigel J

    2010-06-01

    FANCD2, a pivotal protein in the Fanconi anemia and BRCA pathway/network, is monoubiquitylated in the nucleus in response to DNA damage. This study examines the subcellular location and relationship with prognostic factors and patient survival of FANCD2 in breast cancer. Antibodies to FANCD2 were used to immunocytochemically stain 16 benign and 20 malignant breast specimens as well as 314 primary breast carcinomas to assess its association with subcellular compartment and prognostic factors using Fisher's Exact test or with patient survival over 20 years using Wilcoxon-Gehan statistics. Immunoreactive FANCD2 was found in the nucleus and cytoplasm of all 16 benign tissues, but nuclear staining was lost from a significant 19/20 malignant carcinomas (P < 0.0001). Antibodies to FANCD2 stained the cytoplasm of 196 primary carcinomas, leaving 118 as negatively stained. Negative cytoplasmic staining was significantly associated with positive staining for the metastasis-inducing proteins S100A4, S100P, osteopontin, and AGR2 (P < or = 0.002). Survival of patients with FANCD2-negative carcinomas was significantly worse (P < 0.0001) than those with positively stained carcinomas, and only 4% were alive at the census date. Multivariate regression analysis identified negative staining for cytoplasmic FANCD2 as the most significant indicator of patient death (P = 0.001). Thus FANCD2's cytoplasmic loss in the primary carcinomas may allow the selection of cells overexpressing proteins that can induce metastases before surgery.

  16. Diagnostic microRNA markers to screen for sporadic human colon cancer in blood.

    PubMed

    Ahmed, Farid E; Amed, Nancy C; Vos, Paul W; Bonnerup, Chris; Atkins, James N; Casey, Michelle; Nuovo, Gerard J; Naziri, Wade; Wiley, John E; Allison, Ron R

    2012-01-01

    We carried out this study to present proof-of-principal application, showing that by using a global microarray expression analysis, followed by quantitative stem-loop reverse transcriptase in conjunction with TaqMan® polymerase chain reaction (PCR) analysis of micro(mi)RNA genes, on limited number of plasma and tissue samples obtained from 20 individuals (five healthy, five TNM stage 0-1 colon cancer, five stage 2 and five stage 3), we were able to quantitatively monitor miRNA changes at the various TNM stages of colon cancer progression, particularly at the early, pre-malignant adenoma stage (e.g. polyps ≥ 1 cm with high grade dysplasia). The expression of some of the tested miRNAs showed less variability in tissue than in plasma. Nevertheless, our limited preliminary data on the plasma by itself show that plasma is well-suited for screening, and that the quantitative changes in the expression of a few cell-free circulatory mature miRNA molecules in plasma, that are associated with colon cancer progression, would provide for more sensitive and specific markers than those tests currently available on the market. In addition, analysis of miRNA molecules offers a quantitative and cost-effective non-invasive diagnostic approach for screening, than currently employed methods in a prevalent cancer that can be cured if it is detected at the early TNM stages, and that becomes deadly if not diagnosed before metastasis. Thus, a larger prospective and properly randomized clinical study using plasma derived from many control individuals and at various stages of colon cancer (TNM stages 0-IV) from patients, in order to corroborate the initial results, is now urgently needed in order to allow for a statistically valid analysis, standardizing test conditions which will provide a means for determining the true sensitivity and specificity of a miRNA-screening approach. This approach, when combined with bioinformatics analysis to correlate miRNA seed data with mRNA target data, would allow for a mechanistic understanding of how miRNAs regulate mRNA gene expression, and would offer a better comprehensive diagnostic screening test for early-detection of colon cancer non-invasively.

  17. Distinct disruptions of resting-state functional brain networks in familial and sporadic schizophrenia

    PubMed Central

    Zhu, Jiajia; Zhuo, Chuanjun; Liu, Feng; Qin, Wen; Xu, Lixue; Yu, Chunshui

    2016-01-01

    Clinical and brain structural differences have been reported between patients with familial and sporadic schizophrenia; however, little is known about the brain functional differences between the two subtypes of schizophrenia. Twenty-six patients with familial schizophrenia (PFS), 26 patients with sporadic schizophrenia (PSS) and 26 healthy controls (HC) underwent a resting-state functional magnetic resonance imaging. The whole-brain functional network was constructed and analyzed using graph theoretical approaches. Topological properties (including global, nodal and edge measures) were compared among the three groups. We found that PFS, PSS and HC exhibited common small-world architecture of the functional brain networks. However, at a global level, only PFS showed significantly lower normalized clustering coefficient, small-worldness, and local efficiency, indicating a randomization shift of their brain networks. At a regional level, PFS and PSS disrupted different neural circuits, consisting of abnormal nodes (increased or decreased nodal centrality) and edges (decreased functional connectivity strength), which were widely distributed throughout the entire brain. Furthermore, some of these altered network measures were significantly correlated with severity of psychotic symptoms. These results suggest that familial and sporadic schizophrenia had segregated disruptions in the topological organization of the intrinsic functional brain network, which may be due to different etiological contributions. PMID:27032817

  18. Variable Somatic TIE2 Mutations in Half of Sporadic Venous Malformations

    PubMed Central

    Soblet, J.; Limaye, N.; Uebelhoer, M.; Boon, L.M.; Vikkula, M.

    2013-01-01

    Venous malformations (VMs) are the most frequent vascular malformations referred to specialized vascular anomaly centers. A rare (1-2%) familial form, termed cutaneomucosal venous malformation (VMCM), is caused by gain-of-function mutations in TIE2. More recently, sporadic VMs, characterized by the presence of large unifocal lesions, were shown to be caused by somatic mutations in TIE2. These include a frequent L914F change, and a series of double mutations in cis. All of which cause ligand-independent receptor hyperphosphorylation in vitro. Here, we expanded our study to assess the range of mutations that cause sporadic VM. To test for somatic changes, we screened the entire coding region of TIE2 in cDNA from resected VMs by direct sequencing. We detected TIE2 mutations in 17/30 (56.7%) of the samples. In addition to previously detected mutations, we identified 7 novel somatic intracellular TIE2 mutations in sporadic VMs, including 3 that cause premature protein truncation. PMID:23801934

  19. Sporadic and Familial Congenital Cataracts: Mutational Spectrum and New Diagnoses Using Next‐Generation Sequencing

    PubMed Central

    Ma, Alan S.; Grigg, John R.; Ho, Gladys; Prokudin, Ivan; Farnsworth, Elizabeth; Holman, Katherine; Cheng, Anson; Billson, Frank A.; Martin, Frank; Fraser, Clare; Mowat, David; Smith, James; Christodoulou, John; Flaherty, Maree; Bennetts, Bruce

    2016-01-01

    ABSTRACT Congenital cataracts are a significant cause of lifelong visual loss. They may be isolated or associated with microcornea, microphthalmia, anterior segment dysgenesis (ASD) and glaucoma, and there can be syndromic associations. Genetic diagnosis is challenging due to marked genetic heterogeneity. In this study, next‐generation sequencing (NGS) of 32 cataract‐associated genes was undertaken in 46 apparently nonsyndromic congenital cataract probands, around half sporadic and half familial cases. We identified pathogenic variants in 70% of cases, and over 68% of these were novel. In almost two‐thirds (20/33) of these cases, this resulted in new information about the diagnosis and/or inheritance pattern. This included identification of: new syndromic diagnoses due to NHS or BCOR mutations; complex ocular phenotypes due to PAX6 mutations; de novo autosomal‐dominant or X‐linked mutations in sporadic cases; and mutations in two separate cataract genes in one family. Variants were found in the crystallin and gap junction genes, including the first report of severe microphthalmia and sclerocornea associated with a novel GJA8 mutation. Mutations were also found in rarely reported genes including MAF, VIM, MIP, and BFSP1. Targeted NGS in presumed nonsyndromic congenital cataract patients provided significant diagnostic information in both familial and sporadic cases. PMID:26694549

  20. Sporadic isolates of Escherichia coli O157.H7 investigated by pyrolysis mass spectrometry.

    PubMed Central

    Freeman, R.; Sisson, P. R.; Jenkins, D. R.; Ward, A. C.; Lightfoot, N. F.; O'Brien, S. J.

    1995-01-01

    Thirty-six encoded isolates of Escherichia coli. 32 of which were of serotype O157, were examined by pyrolysis mass spectrometry (PyMS). Thirty-one of the serotype O157 isolates possessed the flagellar antigen H7 and produced Verocytotoxin (VT), the other isolate serotyped as H45 and was non-toxigenic. Eighteen of the VT-producing E. coli (VTEC) isolates were from sporadic disease in residents of the Northern Region. Standard principal component (PC) and canonical variate (CV) analysis of the data distinguished only the four non-O157 isolates from the remainder which were indistinguishable by this approach. A similarity matrix based on differences between individual CV means distinguished a further ten isolates. The matrix correctly clustered 2 pairs of isolates from siblings and 4 isolates from an affected family. A further 5 clusters of 3 or more isolates and 6 pairs of isolates were defined. These groupings proved to be homogenous for toxin phenotype but occasionally entrained isolates of dissimilar phage type. However, in general, PyMS-derived clustering of apparently sporadic isolates accorded with geographical locations as determined by postcode. PyMS, which is a quick and high volume capacity phenotypic technique, may be a useful addition to existing methods in the investigation of the epidemiology of sporadic VTEC disease. PMID:7781731

  1. Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome.

    PubMed

    Schell, U; Hehr, A; Feldman, G J; Robin, N H; Zackai, E H; de Die-Smulders, C; Viskochil, D H; Stewart, J M; Wolff, G; Ohashi, H

    1995-03-01

    Pfeiffer syndrome (PS) is an autosomal dominant skeletal disorder which affects the bones of the skull, hands and feet. Previously, we have mapped PS in a subset of families to chromosome 8cen by linkage analysis and demonstrated a common mutation in the fibroblast growth factor receptor-1 (FGFR1) gene in the linked families. Here we report a second locus for PS on chromosome 10q25, and present evidence that mutations in the fibroblast growth factor receptor-2 (FGFR2) gene on 10q25 cause PS in an additional subset of familial and sporadic cases. Three different point mutations in FGFR2, which alter the same acceptor splice site of exon B, were observed in both sporadic and familial PS. In addition, a T to C transition in exon B predicting a cysteine to arginine substitution was identified in three sporadic PS individuals. Interestingly, this T to C change is identical to a mutation in FGFR2 previously reported in Crouzon syndrome, a phenotypically similar disorder but one lacking the hand and foot anomalies seen in PS. Our results highlight the genetic heterogeneity in PS and suggest that the molecular data will be an important complement to the clinical phenotype in defining craniosynostosis syndromes.

  2. [AIP mutations in familial and sporadic pituitary adenomas: local experience and review of the literature].

    PubMed

    Fajardo-Montañana, Carmen; Daly, Adrian F; Riesgo-Suárez, Pedro; Gómez-Vela, José; Tichomirowa, María A; Camara-Gómez, Rosa; Beckers, Albert

    2009-01-01

    Clinically relevant pituitary adenomas occur 3-5 times more frequently than previously thought. The majority are isolated cases, but their presentation can be familial in the setting of known syndromes such as multiple endocrine neoplasia (MEN)-1 and Carney complex. When 2 or more cases of pituitary adenomas occur in the same family in the absence of the above-mentioned syndromes, a diagnosis of FIPA (familial isolated pituitary adenomas) is made, which accounts for 1-2% of all pituitary adenomas. Mutations of the gene AIP (aryl hydrocarbon receptor-interacting protein) may account for 15% of FIPA families (50% of familial acromegaly), and as such the genetic causes continue to be studied. Also mutations in AIP can be detected in sporadic adenomas among young populations (< 30 years of age). We describe the characteristics of FIPA, detailing the study of a spanish family, in this case AIP mutation negative. Also, the reported findings in sporadic adenomas in the young population are detailed, accompanied by the description of a 19- year old patient with an intronic AIP mutation. Multicenter studies have provided understanding of aspects such as mutations in AIP; however, further studies are necessary to identify other genes involved in FIPA and sporadic pituitary adenomas occurring at a young age.

  3. Prevalence of mutations in APC, CTNNB1, and BRAF in Tunisian patients with sporadic colorectal cancer.

    PubMed

    Bougatef, Karim; Ouerhani, Slah; Moussa, Amel; Kourda, Nadia; Coulet, Florence; Colas, Chrystelle; Lahely, Yannick Blondeau; Najjar, Tawfik; Ben Jilani, Sarra; Benammar-Elgaaied, Amel; Soubrier, Florent; Marrakchi, Raja

    2008-11-01

    Sporadic colorectal tumorigenesis is caused by alterations in the Wnt (APC, CTNNB1) and Ras pathways. Our objective was to analyze the occurrence of these genetic alterations in relation to tumor and patient characteristics. The prevalence of somatic alteration in the hot-spot regions of the APC, BRAF, and CTNNB1 genes was investigated in 48 unselected and unrelated Tunisian patients with sporadic colorectal cancer, and the association between the molecular features at these genes in relation to tumor and patient characteristics (age at diagnosis, sex, tumor localization, stage, and differentiation) was analyzed. Loss of heterozygosity was observed at the APC locus in 52% of the analyzed tumors. 6 novel mutations were detected by polymerase chain reaction sequencing in the mutation cluster region of the APC gene. No mutations were observed in the CTNNB1 gene in any tumor, but 8% of tumors harbored mutation in the BRAF gene. Clinicopathological analyses showed an association between APC point mutations and the earliest occurrence of sporadic colorectal cancer. The findings confirm the heterogeneity of APC gene alteration and also reveal a particular profile of this pathology among Tunisian patients that confirms the epidemiological data for this country.

  4. Somatic APC inactivation mechanisms in sporadic colorectal cancer cases in Hungary.

    PubMed

    Kámory, Eniko; Olasz, Judit; Csuka, Orsolya

    2008-03-01

    The role of germline inactivation of the adenomatosis polyposis coli (APC) gene in hereditary colorectal cancer is well known, being the most important cause of familial adenomatosus polyposis (FAP) syndrome. Hereditary cases with germline mutations, however, account only for 5-10% of colorectal cancers. The somatic inactivation of this gene has also been observed in sporadic cases. In order to examine the inactivation mechanisms of the APC gene we screened 70 sporadic colorectal cancer cases (27 rectal, 43 intestinal) of different stages for promoter hypermethylation, allelic imbalance (AI) and somatic mutations. The presence of promoter hypermethylation was observed in 21 cases (30%). Fifteen of the examined tumors (21%) showed AI, and also 15 tumors (21%) carried at least one somatic mutation. Thirteen of the detected alterations were novel variations: seven frameshifts, four missense mutations and two polymorphisms. Biallelic inactivation was found in 15 patients (21%). These results suggest that the inactivation of the APC gene is very common in sporadic colorectal cancer, and the main inactivation mechanism of the APC gene is promoter hypermethylation. Allelic imbalance has the same frequency as mutations, and mutations in the APC gene are more common in the early stages and in tumors located in the rectum.

  5. Formation of sporadic E under the influence of AGWs and horizontal background wind

    NASA Astrophysics Data System (ADS)

    Matiashvili, Giorgi; Dalakishvili, Giorgi; Didebulidze, Goderdzi G.

    2016-04-01

    It is shown that the declined propagation of atmospheric gravity waves (AGWs) (with horizontal kx,ky≠0and vertical wavenumbers kz≠0) can influence the horizontal and vertical convergence of heavy metallic ions at the mid-latitude lower thermosphere. In the case of presence of background horizontal wind with velocity close to AGWs horizontal phase velocity and opposite to AGWs horizontal phase velocity occurs the increase of the ions vertical convergence inside regions with spatial scale of half vertical wavelength λz/2 and the formation of the multilayered sporadic E takes place. In order to investigate temporal evolution of processes related with sporadic E formation the 3-D numerical simulations are performed in the following cases (1) horizontal background wind and AGWs are absent, (2) background horizontal wind with arbitrary direction is considered and (3) AGWs and background horizontal wind ae considered along with taking into account ambipolar diffusion. In the cases of presence of AGW the ions/electron convergence in thin dense layers and formation of multi-layered sporadic E is demonstrated. It is shown that the ions/electron density of Es layers also depends on the horizontal and vertical wavelengths of AGWs' velocity perturbations. The vertical spatial location of the horizontal Es layers is determined by the vertical wavelength of AGWs. Acknowledgements: This work has been supported by Shota Rustaveli National Science Foundation grant No 31/81.

  6. C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population

    PubMed Central

    Sabatelli, Mario; Conforti, Francesca Luisa; Zollino, Marcella; Mora, Gabriele; Monsurrò, Maria Rosaria; Volanti, Paolo; Marinou, Kalliopi; Salvi, Fabrizio; Corbo, Massimo; Giannini, Fabio; Battistini, Stefania; Penco, Silvana; Lunetta, Christian; Quattrone, Aldo; Gambardella, Antonio; Logroscino, Giancarlo; Simone, Isabella; Bartolomei, Ilaria; Pisano, Fabrizio; Tedeschi, Gioacchino; Conte, Amelia; Spataro, Rossella; La Bella, Vincenzo; Caponnetto, Claudia; Mancardi, Gianluigi; Mandich, Paola; Sola, Patrizia; Mandrioli, Jessica; Renton, Alan E.; Majounie, Elisa; Abramzon, Yevgeniya; Marrosu, Francesco; Marrosu, Maria Giovanna; Murru, Maria Rita; Sotgiu, Maria Alessandra; Pugliatti, Maura; Rodolico, Carmelo; Moglia, Cristina; Calvo, Andrea; Ossola, Irene; Brunetti, Maura; Traynor, Bryan J.; Borghero, Giuseppe; Restagno, Gabriella; Chiò, Adriano

    2012-01-01

    It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (familial ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1,757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1,523 from mainland Italy. Sixty (3.7%) of 1,624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathogenic repeat expansion. None of the 619 regionally-matched control samples (1,238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had behavioral FTD in addition to ALS. FTD or unspecified dementia was also detected in 19 pedigrees (27.5%) in first-degree relatives of ALS patients. Cases carrying the C9ORF72 hexanucleotide expansion survived one year less than cases who did not carry this mutation. In conclusion, we found that C9ORF72 hexanucloetide repeat expansions represents a sizeable proportion of apparent sporadic ALS in the Italian and Sardinian population, representing by far the commonest mutation in Italy and the second more common in Sardinia. PMID:22418734

  7. Meteor-induced transient sporadic E as inferred from rapid-run ionosonde observations at midlatitudes

    NASA Astrophysics Data System (ADS)

    Maruyama, Takashi; Kato, Hisao; Nakamura, Maho

    2008-09-01

    Observations were made with a rapid-run ionosonde during a 1-month period from the end of July to the end of August 2002 that included the Perseid meteor shower. Ionograms were obtained at 1-minute intervals. All the echo traces below a virtual height of 200 km were hand-scaled for detecting weak and broken traces as well as well-determined sporadic E. Among the scaled E-region traces, a distinct meteor echo persisting for 40 min was observed. This long-duration meteor event was similar to that observed during the Leonid meteor shower in 2001. However the apparent height of the echo traces in the current event first decreased and then increased after equaling the height of a persistent sporadic E layer, while the apparent height of the long-duration meteor echo trace observed in Leonids 2001 remained nearly constant. The descending rate of the meteor echo was approximately 22 m/s, which was considerably greater than that of the tidal ion layer trapped in a downward-moving wind shear node. We ascribe the long-duration meteor echo to a transient and horizontally drifting sporadic E patch generated from meteor trail plasma.

  8. Performance of D-Parameters in Isolating Meteor Showers from the Sporadic Background

    NASA Technical Reports Server (NTRS)

    Moorhead, Althea

    2016-01-01

    It is often necessary to draw a division between meteor showers and the sporadic meteor complex in order to study these components of the meteoroid environment. Meteor showers persist for less than a season and are composed of members with a greater-than-average degree of orbital similarity. The level of orbital similarity is often quantified using so-called D-parameters; a D-parameter cutoff may be employed to define or extract a shower. Depending on the study, this cutoff value may be chosen based on the size of the data-set, the percentage of sporadic meteors within the data-set, or the inclination of the shower in question. We argue that the cutoff value should also reject the strength of the shower compared to the local sporadic background. We therefore present a method for determining, on a per-shower basis, the D-parameter cutoff that limits the false-positive rate to an acceptable percentage. If the false-positive rate exceeds this percentage regardless of cutoff value, we deem the shower to be undetectable in our data. We apply this method to optical meteor observations from the NASA All-Sky and Southern Ontario Meteor Networks and present the detectable meteor showers and their characteristics.

  9. Exon dosage analysis of parkin gene in Chinese sporadic Parkinson's disease.

    PubMed

    Guo, Ji-Feng; Dong, Xiao-Li; Xu, Qian; Li, Nan; Yan, Xin-Xiang; Xia, Kun; Tang, Bei-Sha

    2015-09-14

    Parkin gene mutations are by far the most common mutations in both familial Parkinson's disease (PD) and sporadic PD. Approximately, 50% of parkin mutations is exon dosage mutations (i.e., deletions and duplications of entire exons). Here, we first established a MLPA assay for quick detection of parkin exon rearrangements. Then, we studied parkin exon dosage mutations in 755 Chinese sporadic PDdisease patients using the established MLPA assay. We found that there were 25 (3.3%) patients with exon dosage alterations including deletions and duplications, 20 (11.4%) patients with exon rearrangements in 178 early-onset patients, and 5 (0.86%) patients with exon rearrangement mutations in 579 later-onset patients. The percentage of individuals with parkin dosage mutations is more than 33% when the age at onset is less than 30 years old, but less than 7% when the age at onset is more than 30. In these mutations, deletion is the main mutational style, especially in exon 2-5. Our results indicated that exon dosage mutations in parkin gene might be the main cause for sporadic PD, especially in EOP.

  10. Sporadic cardiac and skeletal myopathy caused by a de novo desmin mutation.

    PubMed

    Park, K Y; Dalakas, M C; Semino-Mora, C; Lee, H S; Litvak, S; Takeda, K; Ferrans, V J; Goldfarb, L G

    2000-06-01

    Desmin myopathy is a familial or sporadic disorder characterized by intracytoplasmic accumulation of desmin in the muscle cells. We and others have previously identified desmin gene mutations in patients with familial myopathy, but close to 45% of the patients do not report previous family history of the disease. The present study was conducted to determine the cause of desmin myopathy in a sporadic patient presenting with symmetrical muscle weakness and atrophy combined with atrioventricular conduction block requiring a permanent pacemaker. A novel heterozygous R406W mutation in the desmin gene was identified by sequencing cDNA and genomic DNA. Expression of a construct containing the patient's mutant desmin cDNA in SW13 (vim-) cells demonstrated a high pathogenic potential of the R406W mutation. This mutation was not found in the patient's father, mother or sister by sequencing and restriction analysis. Testing with five microsatellite markers and four intragenic single nucleotide polymorphisms excluded alternative paternity. Haplotype analysis indicates that the patient's father was germ-line mosaic for the desmin mutation. We conclude that de novo mutations in the desmin gene may be the cause of sporadic forms of desmin-related cardiac and skeletal myopathy.

  11. Genetic analysis of MC1R variants in Chinese Han patients with sporadic Parkinson's disease.

    PubMed

    He, Sihan; Tan, Ting; Song, Zhi; Yuan, Lamei; Deng, Xiong; Ni, Bin; Chen, Yong; Deng, Hao

    2016-01-12

    Parkinson's disease (PD, OMIM 168600) is a neurodegenerative disorder featured by degeneration of melanin-positive dopaminergic neurons. Epidemiologic studies have suggested that PD and malignant melanoma (MM) might share common genetic components. Recently, the p.R160W variant in the melanocortin 1 receptor gene (MC1R, OMIM 155555), a risk factor for MM, has been identified to be associated with PD in Spanish population. To explore whether the MC1R variants are associated with sporadic PD in Chinese population, we designed a case-control comparison study and studied three variants, including rs3212366 (p.F196L), rs33932559 (p.I120T) and rs34090186 (p.R67Q), in the MC1R gene in 512 Chinese Han patients with sporadic PD and 512 age, gender and ethnicity matched normal controls. For rs3212366, only the TT genotype was identified in both PD and control cohorts. For variants rs33932559 and rs34090186, we did not identify any statistically significant difference in either genotypic distribution or allelic distribution between the PD cohort and control cohort, and in addition, we did not identify any related haplotype that would either increase the risk for PD or play a protective role against PD. Our data suggest that none of the three variants of the MC1R gene and related haplotypes be associated with sporadic form of PD in Chinese Han population from Mainland China.

  12. A statistical analysis on the relationship between thunderstorms and the sporadic E Layer over Rome

    NASA Astrophysics Data System (ADS)

    Barta, V.; Scotto, C.; Pietrella, M.; Sgrigna, V.; Conti, L.; Sátori, G.

    2013-11-01

    Meteorological processes (cold fronts, mesoscale convective complexes, thunderstorms) in the troposphere can generate upward propagating waves in the neutral atmosphere affecting the behaviour of the ionosphere. One type of these waves are the internal atmospheric gravity waves (AGWs) which are often generated by thunderstorms. Davis & Johnson (2005) found in low pressure systems that a localized intensification of the sporadic E layer (Es) can be attributed to lightnings. To confirm this result, we have performed two different statistical analysis using the time series of the critical frequency (foEs), the virtual height of the sporadic E layer (h'Es), and meteorological observations (lightnings, Infrared maps) over the ionospheric station of Rome (41.9o N, 12.5o E). In the first statistical analysis, we separated the days of 2009 into two groups: stormy days and fair-weather days, then we studied the occurrence and the properties of the Es separately for the two different groups. No significant differences have been found. In the second case, a superposed epoch analysis (SEA) was used to study the behaviour of the critical frequency and virtual height 100 hours before and after the lightnings. The SEA shows a statistically significant decrease in the critical frequency after the time of the lightnings, which indicates a sudden decrease in the electron density of the sporadic E layer associated with lightnings.

  13. Genomic era diagnosis and management of hereditary and sporadic colon cancer

    PubMed Central

    Esplin, Edward David; Snyder, Michael Paul

    2014-01-01

    The morbidity and mortality attributable to heritable and sporadic carcinomas of the colon are substantial and affect children and adults alike. Despite current colonoscopy screening recommendations colorectal adenocarcinoma (CRC) still accounts for almost 140000 cancer cases yearly. Familial adenomatous polyposis (FAP) is a colon cancer predisposition due to alterations in the adenomatous polyposis coli gene, which is mutated in most CRC. Since the beginning of the genomic era next-generation sequencing analyses of CRC continue to improve our understanding of the genetics of tumorigenesis and promise to expand our ability to identify and treat this disease. Advances in genome sequence analysis have facilitated the molecular diagnosis of individuals with FAP, which enables initiation of appropriate monitoring and timely intervention. Genome sequencing also has potential clinical impact for individuals with sporadic forms of CRC, providing means for molecular diagnosis of CRC tumor type, data guiding selection of tumor targeted therapies, and pharmacogenomic profiles specifying patient specific drug tolerances. There is even a potential role for genomic sequencing in surveillance for recurrence, and early detection, of CRC. We review strategies for diagnostic assessment and management of FAP and sporadic CRC in the current genomic era, with emphasis on the current, and potential for future, impact of genome sequencing on the clinical care of these conditions. PMID:25493239

  14. Fine structure analysis of the WT1 gene in sporadic Wilms tumors

    SciTech Connect

    Varanasi, R.; Bardeesy, N.; Ghahremani, M.; Pelletier, J.; Petruzzi, M.-J.; Nowak, N.; Shows, T.B.; Adam, M.A.; Grundy, P.

    1994-04-26

    Molecular genetic studies indicate that the etiology of Wilms tumor (WT) is complex, involving at least three loci. Germ-line mutations in the tumor suppressor gene, WT1, have been documented in children with WTs and urogenital developmental anomalies. Sporadic tumors constitute the majority (>90%) of WT cases and previous molecular analyses of the WT1 gene have focused only on the DNA-binding domain. Using the single-strand conformational polymorphism (SSCP) assay, the authors analyzed the structural integrity of the entire WT1 gene in 98 sporadic WTs. By PCR-SSCP they find that mutations in the WT1 gene are rare, occurring in only six tumors analyzed. In one sample, two independent intragenic mutations inactivated both WT1 alleles, providing a singular example of two different somatic alterations restricted to the WT1 gene. This case is consistent with the existence of only one tumor suppressor gene at 11p13 involved in the pathogenesis of WTs. The data, together with the previously ascertained occurrence of large deletions/insertions in WT1, define the frequency at which the WT1 gene is altered in sporadic tumors. 36 refs., 3 figs.

  15. Multiple imputation by chained equations for systematically and sporadically missing multilevel data.

    PubMed

    Resche-Rigon, Matthieu; White, Ian R

    2016-09-19

    In multilevel settings such as individual participant data meta-analysis, a variable is 'systematically missing' if it is wholly missing in some clusters and 'sporadically missing' if it is partly missing in some clusters. Previously proposed methods to impute incomplete multilevel data handle either systematically or sporadically missing data, but frequently both patterns are observed. We describe a new multiple imputation by chained equations (MICE) algorithm for multilevel data with arbitrary patterns of systematically and sporadically missing variables. The algorithm is described for multilevel normal data but can easily be extended for other variable types. We first propose two methods for imputing a single incomplete variable: an extension of an existing method and a new two-stage method which conveniently allows for heteroscedastic data. We then discuss the difficulties of imputing missing values in several variables in multilevel data using MICE, and show that even the simplest joint multilevel model implies conditional models which involve cluster means and heteroscedasticity. However, a simulation study finds that the proposed methods can be successfully combined in a multilevel MICE procedure, even when cluster means are not included in the imputation models.

  16. The brain insulin signal transduction system and sporadic (type II) Alzheimer disease: an update.

    PubMed

    Hoyer, S

    2002-03-01

    Nosologically, Alzheimer disease may not be considered to be a single disorder in spite of a common clinical phenotype. Only a small proportion of about 5% to 10% of all Alzheimer cases is due to genetic mutations (type I) whereas the great majority of patients was found to be sporadic in origin. It may be assumed that susceptibility genes along with lifestyle risk factors contribute to the causation of the age-related sporadic Alzheimer disease (type II). In this context, the desensitization of the neuronal insulin receptor similar to not-insulin dependent diabetes mellitus may be of pivotal significance. This abnormality along with a reduction in brain insulin concentration is assumed to induce a cascade-like process of disturbances including cellular glucose, acetylcholine, cholesterol, and ATP associated with abnormalities in membrane pathology and the formation of both amyloidogenic derivatives and hyperphosphorylated tau protein. Sporadic Alzheimer disease may, thus, be considered to be the brain type of diabetes mellitus II. Experimental evidence is provided and discussed.

  17. De novo mutations from sporadic schizophrenia cases highlight important signaling genes in an independent sample.

    PubMed

    Kranz, Thorsten M; Harroch, Sheila; Manor, Orly; Lichtenberg, Pesach; Friedlander, Yechiel; Seandel, Marco; Harkavy-Friedman, Jill; Walsh-Messinger, Julie; Dolgalev, Igor; Heguy, Adriana; Chao, Moses V; Malaspina, Dolores

    2015-08-01

    Schizophrenia is a debilitating syndrome with high heritability. Genomic studies reveal more than a hundred genetic variants, largely nonspecific and of small effect size, and not accounting for its high heritability. De novo mutations are one mechanism whereby disease related alleles may be introduced into the population, although these have not been leveraged to explore the disease in general samples. This paper describes a framework to find high impact genes for schizophrenia. This study consists of two different datasets. First, whole exome sequencing was conducted to identify disruptive de novo mutations in 14 complete parent-offspring trios with sporadic schizophrenia from Jerusalem, which identified 5 sporadic cases with de novo gene mutations in 5 different genes (PTPRG, TGM5, SLC39A13, BTK, CDKN3). Next, targeted exome capture of these genes was conducted in 48 well-characterized, unrelated, ethnically diverse schizophrenia cases, recruited and characterized by the same research team in New York (NY sample), which demonstrated extremely rare and potentially damaging variants in three of the five genes (MAF<0.01) in 12/48 cases (25%); including PTPRG (5 cases), SCL39A13 (4 cases) and TGM5 (4 cases), a higher number than usually identified by whole exome sequencing. Cases differed in cognition and illness features based on which mutation-enriched gene they carried. Functional de novo mutations in protein-interaction domains in sporadic schizophrenia can illuminate risk genes that increase the propensity to develop schizophrenia across ethnicities.

  18. The heat-pipe resembling action of boiling bubbles in endovenous laser ablation

    PubMed Central

    van den Bos, Renate R.; van Ruijven, Peter W. M.; Nijsten, Tamar; Neumann, H. A. Martino; van Gemert, Martin J. C.

    2010-01-01

    Endovenous laser ablation (EVLA) produces boiling bubbles emerging from pores within the hot fiber tip and traveling over a distal length of about 20 mm before condensing. This evaporation-condensation mechanism makes the vein act like a heat pipe, where very efficient heat transport maintains a constant temperature, the saturation temperature of 100°C, over the volume where these non-condensing bubbles exist. During EVLA the above-mentioned observations indicate that a venous cylindrical volume with a length of about 20 mm is kept at 100°C. Pullback velocities of a few mm/s then cause at least the upper part of the treated vein wall to remain close to 100°C for a time sufficient to cause irreversible injury. In conclusion, we propose that the mechanism of action of boiling bubbles during EVLA is an efficient heat-pipe resembling way of heating of the vein wall. PMID:20644976

  19. Functional connectivity changes resemble patterns of pTDP-43 pathology in amyotrophic lateral sclerosis

    PubMed Central

    Schulthess, Ines; Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Del Tredici, Kelly; Ludolph, Albert C.; Kassubek, Jan

    2016-01-01

    ‘Resting-state’ fMRI allows investigation of alterations in functional brain organization that are associated with an underlying pathological process. We determine whether abnormal connectivity in amyotrophic lateral sclerosis (ALS) in a priori-defined intrinsic functional connectivity networks, according to a neuropathological staging scheme and its DTI-based tract correlates, permits recognition of a sequential involvement of functional networks. ‘Resting-state’ fMRI data from 135 ALS patients and 56 matched healthy controls were investigated for the motor network (corresponding to neuropathological stage 1), brainstem (stage 2), ventral attention (stage 3), default mode/hippocampal network (stage 4), and primary visual network (as the control network) in a cross-sectional analysis and longitudinally in a subgroup of 27 patients after 6 months. Group comparison from cross-sectional and longitudinal data revealed significantly increased functional connectivity (p < 0.05, corrected) in all four investigated networks (but not in the control network), presenting as a network expansion that was correlated with physical disability. Increased connectivity of functional networks, as investigated in a hypothesis-driven approach, is characterized by network expansions and resembled the pattern of pTDP-43 pathology in ALS. However, our data did not allow for the recognition of a sequential involvement of functional connectivity networks at the individual level. PMID:27929102

  20. Generation of furosine and color in infant/enteral formula-resembling systems.

    PubMed

    Rufián-Henares, José Angel; García-Villanova, Belén; Guerra-Hernández, Eduardo

    2004-08-25

    The extent of the Maillard reaction was studied by measuring furosine and color formation in infant and enteral formula-resembling model systems prepared by mixing calcium caseinate, laboratory-obtained or commercial whey protein with lactose or dextrinomaltose (ingredients similar to those used in infant and enteral formula manufacture) and heating the mixture at 100, 120, or 140 degrees C for 0-30 min. The furosine determination was performed by HPLC and the color determination by measuring colorimetric parameters L, a, and b in a reflection photometer. The first steps of the Maillard reaction could be followed by furosine determination when initial ingredients had low thermal damage. Hence, furosine may be an indicator of low thermal damage in ingredients with <100 mg/100 g of protein. At the concentrations used in these model systems, similar to those in infant and enteral formulas, furosine values (indirect measure of lysine losses) were higher in lactose than in dextrinomaltose systems, in which only glucose, maltose, maltotriose, and maltotetraose among all of the sugars present showed reactivity with casein. Finally, the advanced steps could be followed by color determination when the initial ingredients had high thermal damage or the model systems were heated at high temperature or for a long time. Among the parameters assayed, b was the most sensitive.

  1. Survival of Pseudomonas aeruginosa exposed to sunlight resembles the phenom of persistence.

    PubMed

    Forte Giacobone, Ana F; Oppezzo, Oscar J

    2015-01-01

    During exposure of Pseudomonas aeruginosa stationary phase cells to natural solar radiation, a reduction in the rate of loss of bacterial viability was observed when survival fractions were lower than 1/10,000. This reduction was independent of the growth medium used and of the initial bacterial concentration, and was also observed when irradiation was performed with artificial UVA radiation (365nm, 47Wm(-2)). These results indicate the presence of a small bacterial subpopulation with increased tolerance to radiation. Such a tolerance is non-heritable, since survival curves comparable to those of the parental strain were obtained from survivors to long-term exposure to radiation. The radiation response described here resembles the phenomenon called persistence, which consists of the presence of a small subpopulation of slow-growing cells which are able to survive antibiotic treatment within a susceptible bacterial population. The condition of persister cells is acquired via a reversible switch and involves active defense systems towards oxidative stress. Persistence is probably responsible for biphasic responses of bacteria to several stress conditions, one of which may be exposure to sunlight. The models currently used to analyze the lethal action of sunlight overestimate the effect of high-dose irradiation. These models could be improved by including the potential formation of persister cells.

  2. Granular cell ameloblastoma: case report of a particular ameloblastoma histologically resembling oncocytoma.

    PubMed

    Matsushita, Yuki; Fujita, Shuichi; Kawasaki, Goro; Hirota, Yoshinosuke; Rokutanda, Satoshi; Yamashita, Kentaro; Yanamoto, Souichi; Ikeda, Tohru; Umeda, Masahiro

    2015-01-01

    Granular cell ameloblastoma is classified as a histological subtype of solid/multicystic ameloblastoma. Usual granular cell ameloblastoma is histologically characterized by granular changes of stellate-like cells located in the inner portion of the epithelial follicles. Here we report a case of another type of granular cell ameloblastoma, showing predominant anastomosing double-stranded trabeculae of granular cells. This type of granular cell ameloblastoma is extremely rare, and the World Health Organization classification does not contain the entity. We tentatively termed it 'anastomosing granular cell ameloblastoma' in this report. The present case suggests the importance of differential diagnosis because the histology of 'anastomosing granular cell ameloblastoma' resembles that of salivary gland oncocytoma rather than that of usual granular cell ameloblastoma. The trabeculae observed in our case continued to the peripheral cells of a small amount of epithelial sheets of plexiform ameloblastoma, and the tumor cells were positive for CK19, which is regarded as an immunohistochemical marker of odontogenic epithelium. Similar to usual granular cell ameloblastoma, the tumor cells had CD68-positive granules. For precise diagnosis of this condition, immunohistochemistry using CK19 and CD68, as well as detailed histological observation, are recommended.

  3. Epidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis

    PubMed Central

    Seidel, Philipp; Remus, Martina; Delacher, Michael; Grigaravicius, Paulius; Reuss, David E.; Frappart, Lucien; von Deimling, Andreas; Feuerer, Markus; Abdollahi, Amir; Frappart, Pierre-Olivier

    2016-01-01

    Nijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report a novel function of Nbn in skin homeostasis. We found that Nbn deficiency in hair follicle (HF) progenitors promoted increased DNA damage signaling, stimulating p16Ink4a up-regulation, Trp53 stabilization and cytokines secretion leading to HF-growth arrest and hair loss. At later stages, the basal keratinocytes layer exhibited also enhanced DNA damage response but in contrast to the one in HF progenitor was not associated with pro-inflammatory cytokines expression, but rather increased proliferation, lack of differentiation and immune response resembling psoriasiform dermatitis. Simultaneous Nbn and Trp53 inactivation significantly exacerbated this phenotype, due to the lack of inhibition of pro-inflammatory cytokines secretion by Trp53. Altogether, we demonstrated novel functions of Nbn in HF maintenance and prevention of skin inflammation and we provide a mechanistic explanation that links cell intrinsic DNA maintenance with large scale morphological tissue alterations. PMID:27050272

  4. Transformation of Face Transplants: Volumetric and Morphologic Graft Changes Resemble Aging After Facial Allotransplantation.

    PubMed

    Kueckelhaus, M; Turk, M; Kumamaru, K K; Wo, L; Bueno, E M; Lian, C G; Alhefzi, M; Aycart, M A; Fischer, S; De Girolami, U; Murphy, G F; Rybicki, F J; Pomahac, B

    2016-03-01

    Facial allotransplantation restores normal anatomy to severely disfigured faces. Although >30 such operations performed worldwide have yielded promising short-term results, data on long-term outcomes remain scarce. Three full-face transplant recipients were followed for 40 months. Severe changes in volume and composition of the facial allografts were noted. Data from computed tomography performed 6, 18 and 36 months after transplantation were processed to separate allograft from recipient tissues and further into bone, fat and nonfat soft tissues. Skin and muscle biopsies underwent diagnostic evaluation. All three facial allografts sustained significant volume loss (mean 19.55%) between 6 and 36 months after transplant. Bone and nonfat soft tissue volumes decreased significantly over time (17.22% between months 6 and 18 and 25.56% between months 6 and 36, respectively), whereas fat did not. Histological evaluations showed atrophy of muscle fibers. Volumetric and morphometric changes in facial allografts have not been reported previously. The transformation of facial allografts in this study resembled aging through volume loss but differed substantially from regular aging. These findings have implications for risk-benefit assessment, donor selection and measures counteracting muscle and bone atrophy. Superior long-term outcomes of facial allotransplantation will be crucial to advance toward future clinical routine.

  5. On Learning Natural-Science Categories That Violate the Family-Resemblance Principle.

    PubMed

    Nosofsky, Robert M; Sanders, Craig A; Gerdom, Alex; Douglas, Bruce J; McDaniel, Mark A

    2017-01-01

    The general view in psychological science is that natural categories obey a coherent, family-resemblance principle. In this investigation, we documented an example of an important exception to this principle: Results of a multidimensional-scaling study of igneous, metamorphic, and sedimentary rocks (Experiment 1) suggested that the structure of these categories is disorganized and dispersed. This finding motivated us to explore what might be the optimal procedures for teaching dispersed categories, a goal that is likely critical to science education in general. Subjects in Experiment 2 learned to classify pictures of rocks into compact or dispersed high-level categories. One group learned the categories through focused high-level training, whereas a second group was required to simultaneously learn classifications at a subtype level. Although high-level training led to enhanced performance when the categories were compact, subtype training was better when the categories were dispersed. We provide an interpretation of the results in terms of an exemplar-memory model of category learning.

  6. Frosted Branch Angiitis Secondary to Familial Mediterranean Fever Resembling Central Retinal Vein Occlusion

    PubMed Central

    Ozdal, Pınar Çakar; Teke, Mehmet Yasin

    2016-01-01

    Purpose. To report a case of unilateral frosted branch angiitis (FBA) resembling central retinal vein occlusion associated with Familial Mediterranean Fever (FMF). Case Report. A 32-year-old woman presented with progressive, painless vision loss in her left eye lasting for 2 days. She was clinically diagnosed with FMF 2 months ago. The best-corrected visual acuity (BCVA) was 20/20 in her right eye and there was light perception in the left. Ophthalmologic examination revealed severe retinal vasculitis showing clinical features of FBA in the left eye. 64 mg/day oral methylprednisolone was started. A significant improvement in retinal vasculitis was observed in two weeks. However, BCVA did not increase significantly due to subhyaloid premacular hemorrhage. Argon laser posterior hyaloidotomy was performed. One week after hyaloidotomy, visual acuity improved to 20/20 and intravitreal hemorrhage disappeared. Four months after the first attack, FBA recurred. Oral methylprednisolone dosage was increased to 64 mg/day and combined with azathioprine 150 mg. At the end of 12-month follow-up, the BCVA was 20/25 and development of epiretinal membrane was observed in the left eye. Conclusions. Frosted branch angiitis may occur with gene abnormalities as an underlying condition. Our case showed that FMF might be a causative disease. PMID:28044118

  7. Ad-hoc KEEN-type Waves and their Occasional Resemblance to KdV Waveforms

    NASA Astrophysics Data System (ADS)

    Tyshetskiy, Yuriy; Afeyan, Bedros

    2005-10-01

    Nonlinear kinetic waves of the KEEN type [1] but constructed with two BGK recipes are tested with 1D Vlasov-Poisson simulation (1DVPS). One is that of Allis [2] as modified by Johnston (unpublished), the other is that of Eliasson and Shukla [3]. Strong kinetic waves survive well, but not weaker ones. The potential wave trains resemble those from the Korteweg-deVries equation. This proves to be natural when charge density variation with electrostatic potential is like a quadratic polynomial. For expositions on the physics of ponderomotively driven KEEN waves, consult presentations by Afeyan and Savchenko, this conference. (Part of this work was performed under the auspices of the U.S. Department of Energy under grant number DE-FG03-NA00059.) [1] B. Afeyan et al., ``Kinetic Electrostatic Electron Nonlinear (KEEN) Waves and their interactions driven by the ponderomotive force of crossing laser beams'', Proc. IFSA (Inertial Fusion Sciences and Applications 2003, Monterey, CA), 213, B. Hammel, D. Meyerhofer, J. Meyer-ter-Vehn and H. Azechi, editors, American Nuclear Society, 2004. [2] W.P. Allis, paper 3 (pp.21-42), in ``In Honor of Philip M. Morse'', ed. H. Feshbach and K. Ingard, MIT Press (1969). [3] B. Eliasson and P.K. Shukla, Phys. Rev. E 71, 046402 (2005)

  8. Primary uterine cervix melanoma resembling malignant peripheral nerve sheath tumor: a case report.

    PubMed

    Pusceddu, Sara; Bajetta, Emilio; Buzzoni, Roberto; Carcangiu, Maria Luisa; Platania, Marco; Del Vecchio, Michele; Ditto, Antonino

    2008-10-01

    A rare variant of malignant melanoma (MM) of the uterine cervix that mimics a malignant peripheral nerve sheath tumor (MPNST) is described. A 43-year-old white woman was admitted to the hospital complaining of genital discharge and vaginal bleeding. Neoadjuvant chemotherapy and total abdominal hysterectomy and bilateral salpingo-ovariectomy plus pelvic lymphadenectomy were performed, and the diagnosis was MPNST, FIGO IIB. Pathological examination showed a diffuse proliferation of amelanotic spindle cells and large, highly atypical, frequently multinucleated, bizarre, and S100-, HMB-45-, vimentin-positive cells. The patient remained disease-free for 43 months, when an abdominal computed tomographic scan showed local polypoid vaginal lesions, with histological features of typical MM. A pathological review was obtained in our institution by a gynecological pathologist, who defined the primary neoplasm in the cervix as an MM, with a pattern of growth histologically simulating an MPNST, metastatic to the vagina. To our knowledge, this is the first report in literature of MM of the uterine cervix resembling MPNST. Despite its rarity, this variant of MM should be considered when a diagnosis of cervix MPNST is made. The histological and immunohistochemical features of these different entities should be considered in the differential diagnosis.

  9. Manothermosonication of foods and food-resembling systems: effect on nutrient content and nonenzymatic browning.

    PubMed

    Vercet, A; Burgos, J; López-Buesa, P

    2001-01-01

    The effect of manothermosonication (MTS), an emergent technology for food preservation, on thiamin, riboflavin, carotenoids, and ascorbic acid was evaluated in milk and orange juice. The effect of both heat treatment and MTS on several compounds produced in nonenzymatic browning in model systems was also studied. MTS does not affect significantly the nutrient content studied. However, it changes the behavior of nonenzymatic browning. No formation of 5-(hydroxymethyl)-2-furfuraldehyde (HMF) was detected in fruit juice model systems after heat and MTS treatments at the experimental conditions used. In a milk-resembling system, free HMF formation by MTS is higher compared to that by heat treatment. As the MTS temperature increases, free HMF production by both treatments equaled on another. For bound HMF the production rate is lower by MTS than by heat treatment under the experimental conditions used. Formation kinetics of brown pigments and that of fluorescent compounds are different for both treatments. Fluorescence and brown pigment production are faster in MTS.

  10. Silica deposits on Mars with features resembling hot spring biosignatures at El Tatio in Chile.

    PubMed

    Ruff, Steven W; Farmer, Jack D

    2016-11-17

    The Mars rover Spirit encountered outcrops and regolith composed of opaline silica (amorphous SiO2·nH2O) in an ancient volcanic hydrothermal setting in Gusev crater. An origin via either fumarole-related acid-sulfate leaching or precipitation from hot spring fluids was suggested previously. However, the potential significance of the characteristic nodular and mm-scale digitate opaline silica structures was not recognized. Here we report remarkably similar features within active hot spring/geyser discharge channels at El Tatio in northern Chile, where halite-encrusted silica yields infrared spectra that are the best match yet to spectra from Spirit. Furthermore, we show that the nodular and digitate silica structures at El Tatio that most closely resemble those on Mars include complex sedimentary structures produced by a combination of biotic and abiotic processes. Although fully abiotic processes are not ruled out for the Martian silica structures, they satisfy an a priori definition of potential biosignatures.

  11. Evidence of environmental suppression of familial resemblance: height among US Civil War brothers.

    PubMed

    Lauderdale, D S; Rathouz, P J

    1999-01-01

    This study examines, with historical data, whether within family correlations in height varied across environments and whether variability in height was greater in worse environments. To investigate these hypotheses, brothers were identified who were mustered into the Union Army of the US Civil War, using linked records from the 1850 and 1860 censuses and military and medical records. Heights were available for 3898 men aged 18 and older, of whom 595 were further identified as belonging to 288 family sets of two, three or four brothers. Generalized estimating equations were used to concurrently model the mean height, the variance and the correlation between brothers as a function of county population. Heights decreased as county population size increased (p<0.001). The correlation between brothers' heights decreased significantly (p = 0.032) with increasing county population, and the variance increased (p = 0.026). The correlation ranged approximately from 0.63 in the least populous to 0.24 in the most populous counties. The degree of familial resemblance was lower in environments where mean height was lower, and the variability in height was greater, suggesting that the environmental contribution to the variability in height is of greater relative importance in populations reared, on average, in worse environments.

  12. Digital redesign of uncertain interval systems based on time-response resemblance via particle swarm optimization.

    PubMed

    Hsu, Chen-Chien; Lin, Geng-Yu

    2009-07-01

    In this paper, a particle swarm optimization (PSO) based approach is proposed to derive an optimal digital controller for redesigned digital systems having an interval plant based on time-response resemblance of the closed-loop systems. Because of difficulties in obtaining time-response envelopes for interval systems, the design problem is formulated as an optimization problem of a cost function in terms of aggregated deviation between the step responses corresponding to extremal energies of the redesigned digital system and those of their continuous counterpart. A proposed evolutionary framework incorporating three PSOs is subsequently presented to minimize the cost function to derive an optimal set of parameters for the digital controller, so that step response sequences corresponding to the extremal sequence energy of the redesigned digital system suitably approximate those of their continuous counterpart under the perturbation of the uncertain plant parameters. Computer simulations have shown that redesigned digital systems incorporating the PSO-derived digital controllers have better system performance than those using conventional open-loop discretization methods.

  13. Neurogenesis in Aplysia californica resembles nervous system formation in vertebrates. [Sponges

    SciTech Connect

    Jacob, M.H.

    1984-05-01

    The pattern of neurogenesis of the central nervous system of Aplysia californica was investigated by (/sup 3/H)thymidine autoradiography. Large numbers of animals at a series of early developmental stages were labeled with (/sup 3/H)thymidine for 24 or 48 hr and were subsequently sampled at specific intervals throughout the life cycle. I found that proliferative zones, consisting of columnar and placodal ectodermal cells, are established in regions of the body wall adjacent to underlying mesodermal cells. Mitosis in the proliferative zones generates a population of cells which leave the surface and migrate inward to join the nearby forming ganglia. Tracing specific (/sup 3/H)thymidine-labeled cells from the body wall to a particular ganglion and within the ganglion over time suggests that the final genomic replication of the neuronal precursors occurs before the cells join the ganglion while glial cell precursors and differentiating glial cells continue to divide within the ganglion for some time. Ultrastructural examination of the morphological features of the few mitosing cells observed within the Aplysia central nervous system supports this interpretation. The pattern of neurogenesis in the Aplysia central nervous system resembles the proliferation of cells in the neural tube and the migration of neural crest and ectodermal placode cells in the vertebrate nervous system but differs from the pattern described for other invertebrates.

  14. Uterine tumor resembling ovarian sex cord tumor. Case report and review of literature.

    PubMed

    Stefanovic, A; Jeremic, K; Kadija, S; Mitrovic, M; Filimonovic, D; Jankovic-Raznatovic, S; Tavcar, J

    2013-01-01

    A uterine tumor resembling an ovarian sex cord tumor (UTROSCT) shows a poly phenotypic immunophenotype with coexpression of epithelial, myoid, and sex cord markers, as well as hormone receptors. The authors present a case of a 59-year-old multiparous woman admitted to the Institute of Gynecology and Obstetrics Clinical Centre of Serbia in January 2010 due to prolonged vaginal bleeding and abdominal discomfort. The vaginal ultrasound showed an enlarged uterus size of 100 x 74 x 81 mm, with extended cavity with an unhomogenic content and myomas sized 54 x 69 mm located in fundus with secondary changes. She underwent abdominal hysterectomy with adnexectomy. Microscopic examination revealed submucosal uterine tumor with variabile histological organization that had anastomotic trabeculae with solid cellular grupations. Rare mitotic figures (2/10 HPF) were found. Additional imunohistochemistry showed immunophenotype: the sex cord areas were positive for vimentin(++), aSMA(++), AE1/AE3(+), PR(+), and ER(+). The poly phenotypic immunophenotype can be useful in differential diagnosis from other neoplasms but also suggests an origin of UTROSCT from uncommitted stem cell enabling for multidirectional differentiation.

  15. Epithelial proliferation in small ducts of salivary cystadenoma resembling atypical ductal hyperplasia of breast.

    PubMed

    Fahim, Lisa; Weinreb, Ilan; Alexander, Cherupushpam; Perez Ordoñez, Bayardo

    2008-09-01

    Salivary gland cystadenomas are cystic neoplasms with diverse architecture and cytology. Cystadenomas may have a considerable intracystic epithelial component, but an epithelial proliferation in small ducts and cysts resembling atypical ductal hyperplasia of breast has not been documented. The patient was a 68-year-old man with a slow growing right submandibular mass. He has no recurrence 13 months after resection. The tumor was polycystic and measured 3.0 x 2.5 x 2.5 cm. The epithelium of the larger cysts was composed of flat, cuboidal, columnar, and apocrine-like cells. Many of the larger cysts showed "Roman bridges", epithelial tufting, and papillae. The smaller cysts and ducts had apocrine-like cells forming secondary glandular lumens. The ductal cells were surrounded by clear myoepithelial cells. Nuclear pleomorphism and hyperchromasia was seen in the apocrine-like cells. Adjacent to the larger cysts, there was an adenomatoid proliferation of small ducts surrounded by myoepithelial cells. No mitotic activity, necrosis, or stromal invasion was identified. The ductal cells were diffusely positive for keratin 7 and androgen receptors with focal expression of keratin 19 and high-molecular weight keratin. S-100, estrogen and progesterone receptors, and BRST-2 were negative in the ductal cells. Recognition of a prominent intraductal epithelial component in cystadenomas is important to avoid a misdiagnosis of cystadenocarcinoma or low-grade salivary duct carcinoma. Cystadenomas join the list of salivary gland lesions with microscopic similarities to primary lesions of the breast.

  16. Ionogram height time intensity observations of descending sporadic E layers at mid-latitude

    NASA Astrophysics Data System (ADS)

    Haldoupis, C.; Meek, C.; Christakis, N.; Pancheva, D.; Bourdillon, A.

    2006-02-01

    A new methodology of ionosonde height time intensity (HTI) analysis is introduced which allows the investigation of sporadic E layer (Es) vertical motion and variability. This technique, which is useful in measuring descent rates and tidal periodicities of Es, is applied on ionogram recordings made during a summer period from solstice to equinox on the island of Milos (36.7°N; 24.5°E). On the average, the ionogram HTI analysis revealed a pronounced semidiurnal periodicity in layer descent and occurrence. It is characterized by a daytime layer starting at 120 km near 06 h local time (LT) and moving downward to altitudes below 100 km by about 18 h LT when a nighttime layer appears above at ˜125 km. The latter moves also downward but at higher descent rates (1.6 2.2 km/h) than the daytime layer (0.8 1.5 km/h). The nighttime Es is weaker in terms of critical sporadic E frequencies (foEs), has a shorter duration, and tends to occur less during times close to solstice. Here, a diurnal periodicity in Es becomes dominant. The HTI plots often show the daytime and nighttime Es connecting with weak traces in the upper E region which occur with a semidiurnal, and at times terdiurnal, periodicity. These, which are identified as upper E region descending intermediate layers (DIL), play an important role in initiating and reinforcing the sporadic E layers below 120 125 km. The observations are interpreted by considering the downward propagation of wind shear convergent nodes that associate with the S2,3 semidiurnal tide in the upper E region and the S1,1 diurnal tide in the lower E region. The daytime sporadic E layer is attributed to the confluence of semidiurnal and diurnal convergent nodes, which may explain the well-known pre-noon daily maximum observed in foEs. The nighttime layer is not well understood, although most likely it is associated with the intrusion of the daytime DIL into the lower E region due to vertical wind shear convergence nodes descending with the

  17. Analysis of the RNASEL Gene in Familial and Sporadic Prostate Cancer

    PubMed Central

    Wang, Liang; McDonnell, Shannon K.; Elkins, David A.; Slager, Susan L.; Christensen, Eric; Marks, Angela F.; Cunningham, Julie M.; Peterson, Brett J.; Jacobsen, Steven J.; Cerhan, James R.; Blute, Michael L.; Schaid, Daniel J.; Thibodeau, Stephen N.

    2002-01-01

    The RNASEL gene on chromosome 1q25 was recently identified as a candidate gene for hereditary prostate cancer (PC). To confirm these findings, we screened 326 patients from 163 families with familial PC for potential germline mutations, by use of conformation-sensitive gel electrophoresis, followed by direct sequence analysis. A total of six variants were identified, including one intronic and five exonic changes (three missense and two silent alterations). There were no unequivocal pathogenic changes. To further test for potential associations between genes and increased risk for disease, the three missense polymorphisms (Ile97Leu, Arg462Gln, and Glu541Asp) were genotyped in 438 patients with familial PC and in 510 population-based control subjects. Association testing revealed no significant differences between patients and control subjects for either the Leu97 variant (χ2 trend test = 1.42; P=.23) or the Asp541 variant (χ2=1.52; P=.22). However, significant differences were detected for the Arg462Gln genotypes (χ2=5.20; P=.02; odds ratio [OR] = 0.54; 95% confidence interval [CI] 0.32–0.91) when the genotype Gln/Gln was compared with Arg/Arg. In subset analyses, associations were also observed in the younger group (age at diagnosis ⩽64 years) (P=.0008; OR=0.29; 95% CI = 0.13–0.66), in node-negative patients (P=.01; OR=0.48; 95% CI 0.27–0.84), patients with stage T1/T2 disease (P=.008; OR=0.39; 95% CI 0.2–0.75), and patients with low-grade disease (P=.01; OR=0.40; 95% CI 0.20–0.78). To evaluate whether this variant was also associated with sporadic PC, we genotyped an additional 499 patients with sporadic PC. Differences in frequency were not detected between patients with sporadic disease and control subjects. However, the same association was observed between patients with familial disease and patients with sporadic disease for the entire group (χ2=4.82; P=.03), as well as in the subset analyses. These results suggest that polymorphic changes

  18. Diagnosing Sporadic Creutzfeldt-Jakob Disease: Accuracy of CSF 14-3-3 Protein Test of the Spinal Fluid

    MedlinePlus

    ... JAKOB DISEASE: ACCURACY OF THE 14-3-3 PROTEIN TEST OF THE SPINAL FLUID This information sheet ... help you understand how the 14-3-3 protein test helps in diagnosing sporadic Creutzfeldt-Jakob disease ( ...

  19. Allele doses of apolipoprotein E type {epsilon}4 in sporadic late-onset Alzheimer`s disease

    SciTech Connect

    Lucotte, G.; Aouizerate, A.; Gerard, N.

    1995-12-18

    Apoliprotein E, type {epsilon}4 allele (ApoE-{epsilon}4) is associated with late-onset sporadic Alzheimer`s disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-{epsilon}4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging. 26 refs., 2 figs., 1 tab.

  20. Co-observation of sporadic K layer and sporadic Na layer at Beijing, China (40.6°N, 116.2°E)

    NASA Astrophysics Data System (ADS)

    Jiao, Jing

    2016-07-01

    A double-laser beam lidar was successfully developed to simultaneously measure K and Na layers at Beijing (40.6°N, 116.2°E) in 2010. Statistical analysis of the parameters of sporadic K (Ks) and sporadic Na (Nas) layers was performed over two years of lidar data, and different characteristics of them were found. The average Ks occurrence (2.9 %) was lower than that of Nas (5.9 %); the Nas occurrence had a maximum (19.3 %) in May-June months and a minimum (1.6 %) in January-February months, while the Ks occurrence had a maximum (4.9 %) in January-February months and a minimum (1.0 %) in September-Octerbor months; most Ks peaks tended to occur around 93 km, which was ~ 2 km lower than that of Nas (~ 95 km); the Ks peak density was often at least one order of magnitude lower than that of Nas; notably, two Ks with high peak densities (> 1000 cm-3) were observed, which was much higher than K density (15-300 cm-3) reported before. The ascending time of Ks was often longer than its descending time, but an opposite trend occurred for Nas. During the 152 cases of joint observation for the K and Na layers, 21 % (32/152) were cases in which Ks and Nas events simultaneously occurred, while 79% (120/152) were cases in which only one layer (K or Na) exhibited a strong Ks or Nas.

  1. S-Nitrosylation of parkin as a novel regulator of p53-mediated neuronal cell death in sporadic Parkinson’s disease

    PubMed Central

    2013-01-01

    Background Mutations in the gene encoding parkin, a neuroprotective protein with dual functions as an E3 ubiquitin ligase and transcriptional repressor of p53, are linked to familial forms of Parkinson’s disease (PD). We hypothesized that oxidative posttranslational modification of parkin by environmental toxins may contribute to sporadic PD. Results We first demonstrated that S-nitrosylation of parkin decreased its activity as a repressor of p53 gene expression, leading to upregulation of p53. Chromatin immunoprecipitation as well as gel-shift assays showed that parkin bound to the p53 promoter, and this binding was inhibited by S-nitrosylation of parkin. Additionally, nitrosative stress induced apoptosis in cells expressing parkin, and this death was, at least in part, dependent upon p53. In primary mesencephalic cultures, pesticide-induced apoptosis was prevented by inhibition of nitric oxide synthase (NOS). In a mouse model of pesticide-induced PD, both S-nitrosylated (SNO-)parkin and p53 protein levels were increased, while administration of a NOS inhibitor mitigated neuronal death in these mice. Moreover, the levels of SNO-parkin and p53 were simultaneously elevated in postmortem human PD brain compared to controls. Conclusions Taken together, our data indicate that S-nitrosylation of parkin, leading to p53-mediated neuronal cell death, contributes to the pathophysiology of sporadic PD. PMID:23985028

  2. C-338A polymorphism of the endothelin-converting enzyme (ECE-1) gene and the susceptibility to sporadic late-onset Alzheimer's disease and coronary artery disease.

    PubMed

    Scacchi, Renato; Gambina, Giuseppe; Broggio, Elisabetta; Ruggeri, Maria; Corbo, Rosa Maria

    2008-01-01

    The human endothelin-converting enzyme (ECE) is involved in beta-amyloid synthesis and regulation of the endothelin-1 (ET-1) vasoconstricting peptide. We investigated the distribution of the C-338A polymorphism of the ECE-1b gene in sporadic late-onset Alzheimer's disease (LOAD) and in coronary artery disease (CAD) to verify its role in the onset of these two complex diseases. Two cohorts of 458 Italian Caucasian LOAD patients and 165 CAD patients were examined for the C-338A polymorphism and compared with respective control samples (260 and 106 subjects, respectively) . The A allele was less present in LOAD patients than in controls, but an at limits statistically significant difference was achieved only in subjects aged less than 80 years, where only the AA genotypes appeared to have a protective role against the onset of the sporadic LOAD. For the overall CAD sample the pattern was similar and significant differences were observed only in subjects non carrying the apolipoprotein E (APOE) e*4 allele, where the A allele carrying genotypes had a protective role against the onset of the disease.

  3. TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson's disease brains.

    PubMed

    Zucchelli, Silvia; Codrich, Marta; Marcuzzi, Federica; Pinto, Milena; Vilotti, Sandra; Biagioli, Marta; Ferrer, Isidro; Gustincich, Stefano

    2010-10-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the Substantia Nigra and the formation of ubiquitin- and alpha-synuclein (aSYN)-positive cytoplasmic inclusions called Lewy bodies (LBs). Although most PD cases are sporadic, families with genetic mutations have been found. Mutations in PARK7/DJ-1 have been associated with autosomal recessive early-onset PD, while missense mutations or duplications of aSYN (PARK1, PARK4) have been linked to dominant forms of the disease. In this study, we identify the E3 ubiquitin ligase tumor necrosis factor-receptor associated factor 6 (TRAF6) as a common player in genetic and sporadic cases. TRAF6 binds misfolded mutant DJ-1 and aSYN. Both proteins are substrates of TRAF6 ligase activity in vivo. Interestingly, rather than conventional K63 assembly, TRAF6 promotes atypical ubiquitin linkage formation to both PD targets that share K6-, K27- and K29- mediated ubiquitination. Importantly, TRAF6 stimulates the accumulation of insoluble and polyubiquitinated mutant DJ-1 into cytoplasmic aggregates. In human post-mortem brains of PD patients, TRAF6 protein colocalizes with aSYN in LBs. These results reveal a novel role for TRAF6 and for atypical ubiquitination in PD pathogenesis.

  4. Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered.

    PubMed

    Braak, Heiko; Bohl, Jürgen R; Müller, Christian M; Rüb, Udo; de Vos, Rob A I; Del Tredici, Kelly

    2006-12-01

    The synucleinopathy known as sporadic Parkinson's disease (PD) is a multisystem disorder that severely damages predisposed nerve cell types in circumscribed regions of the human nervous system. A recent staging procedure for the inclusion body pathology associated with PD proposes that, in the brain, the pathological process (formation of proteinaceous intraneuronal Lewy bodies and Lewy neurites) begins at two sites and continues in a topographically predictable sequence in six stages, during which components of the olfactory, autonomic, limbic, and somatomotor systems become progressively involved. In stages 1 to 2, the Lewy body pathology is confined to the medulla oblongata/pontine tegmentum and anterior olfactory structures. In stages 3 to 4, the substantia nigra and other nuclei of the basal mid- and forebrain become the focus of initially subtle and, then, severe changes. During this phase, the illness probably becomes clinically manifest. In the final stages 5 to 6, the lesions appear in the neocortex. This cross-sectional study originally was performed on 168 autopsy cases using material from 69 incidental cases and 41 clinically diagnosed PD patients as well as 58 age- and gender-matched controls. Here, the staging hypothesis is critically reconsidered and discussed.

  5. Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment.

    PubMed

    Hung, Kenneth E; Maricevich, Marco A; Richard, Larissa Georgeon; Chen, Wei Y; Richardson, Michael P; Kunin, Alexandra; Bronson, Roderick T; Mahmood, Umar; Kucherlapati, Raju

    2010-01-26

    Most genetically engineered mouse (GEM) models for colon cancer are based on tissuewide or germline gene modification, resulting in tumors predominantly of the small intestine. Several of these models involve modification of the adenomatous polyposis coli (Apc) gene and are excellent models for familial cancer predisposition syndromes. We have developed a stochastic somatic mutation model for sporadic colon cancer that presents with isolated primary tumors in the distal colon and recapitulates the entire adenoma-carcinoma-metastasis axis seen in human colon cancer. Using this model, we have analyzed tumors that are either solely mutant in the Apc gene or in combination with another colon cancer-associated mutant gene, the Kras G12D allele. Because of the restricted location in the distal colon, the natural history of the tumors can be analyzed by serial colonoscopy. As the mammalian target of rapamycin (mTOR) pathway is a critical component of the complex signaling network in colon cancer, we used this model to assess the efficacy of mTOR blockade through rapamycin treatment of mice with established tumors. After treatment, Apc mutant tumors were more than 80% smaller than control tumors. However, tumors that possessed both Apc and Kras mutations did not respond to rapamycin treatment. These studies suggest that mTOR inhibitors should be further explored as potential colorectal cancer therapies in patients whose tumors do not have activating mutations in KRAS.

  6. Sporadic Creutzfeldt-Jakob Disease: Prion Pathology in Medulla Oblongata-Possible Routes of Infection and Host Susceptibility.

    PubMed

    Iacono, Diego; Ferrari, Sergio; Gelati, Matteo; Zanusso, Gianluigi; Mariotto, Sara; Monaco, Salvatore

    2015-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disorder, is characterized by remarkable phenotypic variability, which is influenced by the conformation of the pathologic prion protein and the methionine/valine polymorphic codon 129 of the prion protein gene. While the etiology of sCJD remains unknown, it has been hypothesized that environmental exposure to prions might occur through conjunctival/mucosal contact, oral ingestion, inhalation, or simultaneous involvement of the olfactory and enteric systems. We studied 21 subjects with definite sCJD to assess neuropathological involvement of the dorsal motor nucleus of the vagus and other medullary nuclei and to evaluate possible associations with codon 129 genotype and prion protein conformation. The present data show that prion protein deposition was detected in medullary nuclei of distinct sCJD subtypes, either valine homozygous or heterozygous at codon 129. These findings suggest that an "environmental exposure" might occur, supporting the hypothesis that external sources of contamination could contribute to sCJD in susceptible hosts. Furthermore, these novel data could shed the light on possible causes of sCJD through a "triple match" hypothesis that identify environmental exposure, host genotype, and direct exposure of specific anatomical regions as possible pathogenetic factors.

  7. Simultaneous compression and encryption of closely resembling images: application to video sequences and polarimetric images.

    PubMed

    Aldossari, M; Alfalou, A; Brosseau, C

    2014-09-22

    This study presents and validates an optimized method of simultaneous compression and encryption designed to process images with close spectra. This approach is well adapted to the compression and encryption of images of a time-varying scene but also to static polarimetric images. We use the recently developed spectral fusion method [Opt. Lett.35, 1914-1916 (2010)] to deal with the close resemblance of the images. The spectral plane (containing the information to send and/or to store) is decomposed in several independent areas which are assigned according a specific way. In addition, each spectrum is shifted in order to minimize their overlap. The dual purpose of these operations is to optimize the spectral plane allowing us to keep the low- and high-frequency information (compression) and to introduce an additional noise for reconstructing the images (encryption). Our results show that not only can the control of the spectral plane enhance the number of spectra to be merged, but also that a compromise between the compression rate and the quality of the reconstructed images can be tuned. We use a root-mean-square (RMS) optimization criterion to treat compression. Image encryption is realized at different security levels. Firstly, we add a specific encryption level which is related to the different areas of the spectral plane, and then, we make use of several random phase keys. An in-depth analysis at the spectral fusion methodology is done in order to find a good trade-off between the compression rate and the quality of the reconstructed images. Our new proposal spectral shift allows us to minimize the image overlap. We further analyze the influence of the spectral shift on the reconstructed image quality and compression rate. The performance of the multiple-image optical compression and encryption method is verified by analyzing several video sequences and polarimetric images.

  8. Increasing extracellular potassium results in subthalamic neuron activity resembling that seen in a 6-hydroxydopamine lesion.

    PubMed

    Strauss, Ulf; Zhou, Fu-Wen; Henning, Jeannette; Battefeld, Arne; Wree, Andreas; Köhling, Rüdiger; Haas, Stefan Jean-Pierre; Benecke, Reiner; Rolfs, Arndt; Gimsa, Ulrike

    2008-06-01

    Abnormal neuronal activity in the subthalamic nucleus (STN) plays a crucial role in the pathophysiology of Parkinson's disease (PD). Although altered extracellular potassium concentration ([K+]o) and sensitivity to [K+]o modulates neuronal activity, little is known about the potassium balance in the healthy and diseased STN. In vivo measurements of [K+]o using ion-selective electrodes demonstrated a twofold increase in the decay time constant of lesion-induced [K+]o transients in the STN of adult Wistar rats with a unilateral 6-hydroxydopamine (6-OHDA) median forebrain bundle lesion, employed as a model of PD, compared with nonlesioned rats. Various [K+]o concentrations (1.5-12.5 mM) were applied to in vitro slice preparations of three experimental groups of STN slices from nonlesioned control rats, ipsilateral hemispheres, and contralateral hemispheres of lesioned rats. The majority of STN neurons of nonlesioned rats and in slices contralateral to the lesion fired spontaneously, predominantly in a regular pattern, whereas those in slices ipsilateral to the lesion fired more irregularly or even in bursts. Experimentally increased [K+]o led to an increase in the number of spontaneously firing neurons and action potential firing rates in all groups. This was accompanied by a decrease in the amplitude of post spike afterhyperpolarization (AHP) and the amplitude and duration of the posttrain AHP. Lesion effects in ipsilateral neurons at physiological [K+]o resembled the effects of elevated [K+]o in nonlesioned rats. Our data suggest that changed potassium sensitivity due to conductivity alterations and delayed clearance may be critical for shaping STN activity in parkinsonian states.

  9. Parent–offspring resemblance in colony-specific adult survival of cliff swallows

    USGS Publications Warehouse

    Brown, Charles R.; Roche, Erin A.; Brown, Mary Bomberger

    2015-01-01

    Survival is a key component of fitness. Species that occupy discrete breeding colonies with different characteristics are often exposed to varying costs and benefits associated with group size or environmental conditions, and survival is an integrative net measure of these effects. We investigated the extent to which survival probability of adult (≥1-year old) cliff swallows (Petrochelidon pyrrhonota) occupying different colonies resembled that of their parental cohort and thus whether the natal colony had long-term effects on individuals. Individuals were cross-fostered between colonies soon after hatching and their presence as breeders monitored at colonies in the western Nebraska study area for the subsequent decade. Colony-specific adult survival probabilities of offspring born and reared in the same colony, and those cross-fostered away from their natal colony soon after birth, were positively and significantly related to subsequent adult survival of the parental cohort from the natal colony. This result held when controlling for the effect of natal colony size and the age composition of the parental cohort. In contrast, colony-specific adult survival of offspring cross-fostered to a site was unrelated to that of their foster parent cohort or to the cohort of non-fostered offspring with whom they were reared. Adult survival at a colony varied inversely with fecundity, as measured by mean brood size, providing evidence for a survival–fecundity trade-off in this species. The results suggest some heritable variation in adult survival, likely maintained by negative correlations between fitness components. The study provides additional evidence that colonies represent non-random collections of individuals.

  10. The presumed ginkgophyte Umaltolepis has seed-bearing structures resembling those of Peltaspermales and Umkomasiales

    PubMed Central

    Herrera, Fabiany; Shi, Gongle; Ichinnorov, Niiden; Takahashi, Masamichi; Bugdaeva, Eugenia V.; Herendeen, Patrick S.; Crane, Peter R.

    2017-01-01

    The origins of the five groups of living seed plants, including the single relictual species Ginkgo biloba, are poorly understood, in large part because of very imperfect knowledge of extinct seed plant diversity. Here we describe well-preserved material from the Early Cretaceous of Mongolia of the previously enigmatic Mesozoic seed plant reproductive structure Umaltolepis, which has been presumed to be a ginkgophyte. Abundant new material shows that Umaltolepis is a seed-bearing cupule that was borne on a stalk at the tip of a short shoot. Each cupule is umbrella-like with a central column that bears a thick, resinous, four-lobed outer covering, which opens from below. Four, pendulous, winged seeds are attached to the upper part of the column and are enclosed by the cupule. Evidence from morphology, anatomy, and field association suggests that the short shoots bore simple, elongate Pseudotorellia leaves that have similar venation and resin ducts to leaves of living Ginkgo. Umaltolepis seed-bearing structures are very different from those of Ginkgo but very similar to fossils described previously as Vladimaria. Umaltolepis and Vladimaria do not closely resemble the seed-bearing structures of any living or extinct plant, but are comparable in some respects to those of certain Peltaspermales and Umkomasiales (corystosperms). Vegetative similarities of the Umaltolepis plant to Ginkgo, and reproductive similarities to extinct peltasperms and corystosperms, support previous ideas that Ginkgo may be the last survivor of a once highly diverse group of extinct plants, several of which exhibited various degrees of ovule enclosure. PMID:28265050

  11. Analgesic and toxic effects of ABT-594 resemble epibatidine and nicotine in rats.

    PubMed

    Boyce, S; Webb, J K; Shepheard, S L; Russell, M G; Hill, R G; Rupniak, N M

    2000-04-01

    The present study directly compared the antinociceptive and toxic effects of the neuronal nicotinic receptor agonist ABT-594 ((R)-5-(2-azetidinylmethoxy)-2-chloropyridine) with (-)-nicotine and (+)-epibatidine. Like (-)-nicotine (0.8 and 1.6 mg/kg s.c.) and (+)-epibatidine (0.005 and 0.01 mg/kg s.c.), ABT-594 (0.05 and 0.1 mg/kg s.c.) increased response latencies in the hot-plate test in rats, indicating that it has antinociceptive activity. In contrast to (-)-nicotine and (+)-epibatidine, ABT-594 did not cause rotarod impairment at antinociceptive doses but did cause hypothermia and life-threatening adverse effects including seizures. ABT-594 (0.01 and 0.1 mg/kg i.v.) also produced a dose-dependent increase in blood pressure resembling that observed with (-)-nicotine (0.03, 0.1 and 0. 03 mg/kg i.v.) and (+)-epibatidine (0.001 and 0.003 mg/kg i.v.). Both the antinociceptive and toxic effects (convulsions and hypertension) were abolished by pretreatment with the brain penetrant neuronal nAChR antagonist mecamylamine (1 mg/kg s.c.; i.v. for cardiovascular studies), demonstrating that these actions of ABT-594 were mediated via activation of neuronal nicotinic receptors. Continuous infusion of ABT-594 (0.2 mg/kg per day s.c.) to rats for 7 days followed by challenge with mecamylamine (1 mg/kg i.p.) induced a nicotine-like abstinence syndrome suggesting that ABT-594 has nicotine-like dependence liability. These findings indicate that the acute safety profile of ABT-594 is not significantly improved over other nicotinic analgesics.

  12. Ventricular Tachycardia and Resembling Acute Coronary Syndrome During Pheochromocytoma Crisis: A Case Report.

    PubMed

    Li, Shi-Jun; Wang, Tao; Wang, Lin; Pang, Zhan-Qi; Ma, Ben; Li, Ya-Wen; Yang, Jian; Dong, He

    2016-04-01

    Pheochromocytomas are neuroendocrine tumors, and its cardiac involvement may include transient myocardial dysfunction, acute coronary syndrome (ACS), and even ventricular arrhythmias.A patient was referred for evaluation of stuttering chest pain, and his electrocardiogram showed T-wave inversion over leads V1 to V4. Coronary angiography showed 90% stenosis in the mid-left anterior descending coronary artery (LAD), which was stented. Five days later, the patient had ventricular tachycardia, and severe hypertension, remarkable blood pressure fluctuation between 224/76 and 70/50 mm Hg. The patient felt abdominal pain and his abdominal ultrasound showed suspicious right adrenal gland tumor. Enhanced computed tomography of adrenal gland conformed that there was a tumor in right adrenal gland accompanied by an upset level of aldosterone.The tumor was removed by laparoscope, and the pathological examination showed pheochromocytoma. After the surgery, the blood pressure turned normal gradually. There was no T-wave inversion in lead V1-V4. Our case illustrates a rare pheochromocytoma presentation with a VT and resembling ACS. In our case, the serious stenosis in the mid of LAD could be explained by worsen the clinical course of myocardial ischemia or severe coronary vasospasm by the excessive amounts of catecholamines released from the tumor. Coronary vasospasm was possible because he had no classic coronary risk factors (e.g. family history and smoking habit, essential hypertension, hyperglycemia and abnormal serum lipoprotein, high body mass index). Thus, pheochromocytoma was missed until he revealed the association of his symptoms with abdominalgia.As phaeochromocytomas that present with cardiovascular complications can be fatal, it is necessary to screen for the disease when patients present with symptoms indicating catecholamine excess.

  13. Underediting of GluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, does not occur in motor neurons in ALS1 or SBMA.

    PubMed

    Kawahara, Yukio; Sun, Hui; Ito, Kyoko; Hideyama, Takuto; Aoki, Masashi; Sobue, Gen; Tsuji, Shoji; Kwak, Shin

    2006-01-01

    Deficient RNA editing of the AMPA receptor subunit GluR2 at the Q/R site is a primary cause of neuronal death and recently has been reported to be a tightly linked etiological cause of motor neuron death in sporadic amyotrophic lateral sclerosis (ALS). We quantified the RNA editing efficiency of the GluR2 Q/R site in single motor neurons of rats transgenic for mutant human Cu/Zn-superoxide dismutase (SOD1) as well as patients with spinal and bulbar muscular atrophy (SBMA), and found that GluR2 mRNA was completely edited in all the motor neurons examined. It seems likely that the death cascade is different among the dying motor neurons in sporadic ALS, familial ALS with mutant SOD1 and SBMA.

  14. Case-control studies of sporadic enteric infections: a review and discussion of studies conducted internationally from 1990 to 2009.

    PubMed

    Fullerton, Kathleen E; Scallan, Elaine; Kirk, Martyn D; Mahon, Barbara E; Angulo, Frederick J; de Valk, Henriette; van Pelt, Wilfrid; Gauci, Charmaine; Hauri, Anja M; Majowicz, Shannon; O'Brien, Sarah J

    2012-04-01

    Epidemiologists have used case-control studies to investigate enteric disease outbreaks for many decades. Increasingly, case-control studies are also used to investigate risk factors for sporadic (not outbreak-associated) disease. While the same basic approach is used, there are important differences between outbreak and sporadic disease settings that need to be considered in the design and implementation of the case-control study for sporadic disease. Through the International Collaboration on Enteric Disease "Burden of Illness" Studies (the International Collaboration), we reviewed 79 case-control studies of sporadic enteric infections caused by nine pathogens that were conducted in 22 countries and published from 1990 through to 2009. We highlight important methodological and study design issues (including case definition, control selection, and exposure assessment) and discuss how approaches to the study of sporadic enteric disease have changed over the last 20 years (e.g., making use of more sensitive case definitions, databases of controls, and computer-assisted interviewing). As our understanding of sporadic enteric infections grows, methods and topics for case-control studies are expected to continue to evolve; for example, advances in understanding of the role of immunity can be used to improve control selection, the apparent protective effects of certain foods can be further explored, and case-control studies can be used to provide population-based measures of the burden of disease.

  15. Conditional Loss of Arx From the Developing Dorsal Telencephalon Results in Behavioral Phenotypes Resembling Mild Human ARX Mutations

    PubMed Central

    Simonet, Jacqueline C.; Sunnen, C. Nicole; Wu, Jue; Golden, Jeffrey A.; Marsh, Eric D.

    2015-01-01

    Mutations in the Aristaless-Related Homeobox (ARX) gene cause structural anomalies of the brain, epilepsy, and neurocognitive deficits in children. During forebrain development, Arx is expressed in both pallial and subpallial progenitor cells. We previously demonstrated that elimination of Arx from subpallial-derived cortical interneurons generates an epilepsy phenotype with features overlapping those seen in patients with ARX mutations. In this report, we have selectively removed Arx from pallial progenitor cells that give rise to the cerebral cortical projection neurons. While no discernable seizure activity was recorded, these mice exhibited a peculiar constellation of behaviors. They are less anxious, less social, and more active when compared with their wild-type littermates. The overall cortical thickness was reduced, and the corpus callosum and anterior commissure were hypoplastic, consistent with a perturbation in cortical connectivity. Taken together, these data suggest that some of the structural and behavioral anomalies, common in patients with ARX mutations, are specifically due to alterations in pallial progenitor function. Furthermore, our data demonstrate that some of the neurobehavioral features found in patients with ARX mutations may not be due to on-going seizures, as is often postulated, given that epilepsy was eliminated as a confounding variable in these behavior analyses. PMID:24794919

  16. Hippocampal activation, memory performance in young and old, and the risk for sporadic Alzheimer’s disease converge genetically to calcium signaling

    PubMed Central

    Heck, Angela; Fastenrath, Matthias; Coynel, David; Auschra, Bianca; Bickel, Horst; Freytag, Virginie; Gschwind, Leo; Hartmann, Francina; Jessen, Frank; Kaduszkiewicz, Hanna; Maier, Wolfgang; Milnik, Annette; Pentzek, Michael; Riedel-Heller, Steffi G.; Spalek, Klara; Vogler, Christian; Wagner, Michael; Weyerer, Siegfried; Wolfsgruber, Steffen; de Quervain, Dominique F.; Papassotiropoulos, Andreas

    2017-01-01

    Importance Human episodic memory performance is linked to the function of specific brain regions, including the hippocampus, declines as a result of increasing age, and is markedly disturbed in Alzheimer’s disease (AD), an age-associated neurodegenerative disorder affecting primarily the hippocampus. Exploring the molecular underpinnings of human episodic memory is key to the understanding of hippocampus-dependent cognitive physiology and pathophysiology. Objective To determine whether biologically defined groups of genes are enriched in episodic memory performance across ages, in memory encoding-related brain activity and in AD. Design, Setting, and Participants In this multicenter collaborative study, gene set enrichment analysis was done by using primary and meta-analysis data from 57968 participants. The Swiss cohorts consisted of 3043 healthy young adults assessed for episodic memory performance. In a subgroup (1119 participants) of one of these cohorts, functional magnetic resonance imaging (fMRI) was used to identify gene set-dependent differences in brain activity related to episodic memory. The German AgeCoDe cohort consisted of 763 non-demented elderly participants assessed for episodic memory performance. The International Genomics of Alzheimer's Project (IGAP) case-control sample consisted of 54162 participants (17008 patients with sporadic AD, 37154 controls). Main Outcomes and Measures Gene set enrichment analysis in all samples was done by using genome-wide single nucleotide polymorphism (SNP) data. Episodic memory performance in the Swiss and AgeCoDe cohorts was quantified by picture and verbal delayed free recall tasks. In the fMRI experiment, activation of the hippocampus during encoding of pictures served as the phenotype of interest. In the IGAP sample, diagnosis of sporadic AD served as the phenotype of interest. Results We detected significant and consistent enrichment for genes constituting the Calcium Signaling Pathway (KEGG entry: hsa

  17. Resemblance of dinner meals consumption among mother and preschool-aged child dyads from families with limited incomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Parents’ eating habits are associated with food and nutrient intake of their children; yet, the associations have not always been very strong. The objective of this study was to expand the current literature to include an examination of resemblance in intakes of foods, within the context of a meal, ...

  18. Mimicry on the edge: why do mimics vary in resemblance to their model in different parts of their geographical range?

    PubMed

    Harper, George R; Pfennig, David W

    2007-08-22

    Batesian mimics-benign species that predators avoid because they resemble a dangerous species-often vary geographically in resemblance to their model. Such geographical variation in mimic-model resemblance may reflect geographical variation in model abundance. Natural selection should favour even poor mimics where their model is common, but only good mimics where their model is rare. We tested these predictions in a snake-mimicry complex where the geographical range of the mimic extends beyond that of its model. Mimics on the edge of their model's range (where the model was rare) resembled the model more closely than did mimics in the centre of their model's range (where the model was common). When free-ranging natural predators on the edge of the model's range were given a choice of attacking replicas of good or poor mimics, they avoided only good mimics. By contrast, those in the centre of the model's range attacked good and poor mimics equally frequently. Generally, although poor mimics may persist in areas where their model is common, only the best mimics should occur in areas where their model is rare. Thus, counter-intuitively, the best mimics may occur on the edge of their model's range.

  19. The resemblance of an autocorrelation function to a power spectrum density for a spike train of an auditory model

    NASA Astrophysics Data System (ADS)

    Ushakov, Y. V.; Dubkov, A. A.; Spagnolo, B.

    2013-01-01

    In this work we develop an analytical approach for calculation of the all-order interspike interval density (AOISID), show its connection with the autocorrelation function, and try to explain the discovered resemblance of AOISID to the power spectrum of the same spike train.

  20. Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy

    PubMed Central

    Esslinger, Ulrike; Garnier, Sophie; Korniat, Agathe; Proust, Carole; Kararigas, Georgios; Müller-Nurasyid, Martina; Empana, Jean-Philippe; Morley, Michael P.; Perret, Claire; Stark, Klaus; Bick, Alexander G.; Prasad, Sanjay K.; Kriebel, Jennifer; Li, Jin; Tiret, Laurence; Strauch, Konstantin; O'Regan, Declan P.; Marguiles, Kenneth B.; Seidman, Jonathan G.; Boutouyrie, Pierre; Lacolley, Patrick; Jouven, Xavier; Hengstenberg, Christian; Komajda, Michel; Hakonarson, Hakon; Isnard, Richard; Arbustini, Eloisa; Grallert, Harald; Cook, Stuart A.; Seidman, Christine E.; Regitz-Zagrosek, Vera; Cappola, Thomas P.; Charron, Philippe; Cambien, François; Villard, Eric

    2017-01-01

    Aims Dilated cardiomyopathy (DCM) is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS) to assess the contribution of missense variants to sporadic DCM. Methods and results 116,855 single nucleotide variants (SNVs) were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCM-associated loci (Q-value<0.01). The lead-SNVs at novel loci are common and located in TTN, SLC39A8, MLIP, FLNC, ALPK3 and FHOD3. In silico fine mapping identified HSPB7 as the most likely candidate at the ZBTB17 locus. Rare variant analysis (MAF<0.01) demonstrated significant association for TTN variants only (P = 0.0085). All candidate genes but one (SLC39A8) exhibit preferential expression in striated muscle tissues and mutations in TTN, BAG3, FLNC and FHOD3 are known to cause familial cardiomyopathy. We also investigated a panel of 48 known cardiomyopathy genes. Collectively, rare (n = 228, P = 0.0033) or common (n = 36, P = 0.019) variants with elevated in silico severity scores were associated with DCM, indicating that the spectrum of genes contributing to sporadic DCM extends beyond those identified here. Conclusion We identified eight loci independently associated with sporadic DCM. The functions of the best candidate genes at these loci suggest that proteostasis regulation might play a role in DCM pathophysiology. PMID:28296976

  1. Microsatellite instability at tetranucleotide repeats in sporadic colorectal cancer in Japan.

    PubMed

    Yamada, Kanae; Kanazawa, Shinsaku; Koike, Junichi; Sugiyama, Hisahiko; Xu, Can; Funahashi, Kimihiko; Boland, C Richard; Koi, Minoru; Hemmi, Hiromichi

    2010-02-01

    Most tumors of patients with Lynch syndrome and a fraction of sporadic colorectal cancers (CRCs) exhibit high levels of microsatellite instability (MSI) at mono- and dinucleotide repeat loci. A different type of instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has been found in non-colonic cancers. Our previous study demonstrated that EMAST is common in sporadic CRC. Here, we focused on the relationships between EMAST and other genomic instability parameters or clinicopathological features in an unselected series of 88 sporadic CRCs. Of the tumors in the sample, 4 (4.5%) were MSI-high (MSI-H), 9 (10.2%) were MSI-low (MSI-L) and 75 (85.2%) were microsatellite stable. EMAST status was determined using 7 EMAST markers. Fifty-three (60.2%) tumors without MSI-H showed instability at >or=1 EMAST loci. All 4 MSI-H tumors showed instability at several EMAST loci. Instability profiles of MSI-H tumors at EMAST loci were more complex than those of non-MSI-H tumors. A tendency of positive association was observed between MSI-L and EMAST (P=0.023). The frequency of loss of heterozygosity (LOH) for the 14 loci in EMAST-positive tumors was significantly higher than negative tumors (P=0.048). Among the clinicopathological parameters, only tumor location at the distal colon was associated with EMAST-negative tumors (P=0.0084, one-tailed). A relatively higher frequency of well-differentiated adenocarcinomas was observed in EMAST tumors as opposed to non-EMAST tumors, though the survival rate was similar. These results suggest that overlapping mechanisms that cause MSI-L, EMAST and LOH in CRCs may exist.

  2. Family History of Cancer and Risk of Sporadic Differentiated Thyroid Carcinoma

    PubMed Central

    Xu, Li; Li, Guojun; Wei, Qingyi; El-Naggar, Adel K.; Sturgis, Erich M.

    2011-01-01

    BACKGROUND Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since 1980s. While the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid cancer (DTC). Therefore, we explored the association between sporadic DTC and family history of cancer. METHODS In a retrospective hospital-based case-control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first-degree family history of cancer. RESULTS The study included 288 patients with sporadic DTC and 591 cancer-free controls. Family history of thyroid cancer in first-degree relatives was associated with increased DTC risk (adjusted OR = 4.1, 95% CI: 1.7–9.9). All DTC cases in patients with a first-degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR = 4.6, 95 CI%: 1.9–11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR = 7.4, 95% CI: 1.8–30.4). In addition, multifocal primary tumor was more common among PTC patients with first-degree family history of thyroid cancer than among PTC patients with no first-degree family history of thyroid cancer (68.8% vs. 35.5%, p = 0.01). CONCLUSIONS Our study suggests that family history of thyroid cancer in first-degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC. PMID:21800288

  3. Tidal wind as a possible link of coupling between atmospheric waves activity and sporadic E formation

    NASA Astrophysics Data System (ADS)

    Dalakishvili, Giorgi; Didebulidze, Goderdzi G.; Matiashvili, Giorgi

    2016-04-01

    The horizontal tidal wind in the mesosphere lower thermosphere region (MLT) is considered as a source of atmospheric gravity waves (AGWs) and vortical type perturbations generation. It is shown that at mid-latitude these atmospheric waves, evolving in the tidal wind, can lead to vertical convergence of heavy metallic ions of this region and Formation of sporadic E (Es) layer. The process of sporadic E formation by short-period AGWs (close to Bunt-Vaisala period) and by the stationary type vortical perturbations with the same spatial scale, excited in the horizontal shear flow is demonstrated using numerical simulations. The possibility of oscillation of Es layers electron/ions density by period less than BV period under influence of short-period AGWs is shown and the possible coupling of these processes with quasi-periodic echoes is also noted. In our numerical experiment the mid-latitude nighttime Es layers formed under influence of these atmospheric waves, which are possibly generated by horizontal tidal wind, mostly move downward, this is an observed phenomena. It is noted that investigation of sporadic E formation by atmospheric waves evolving in the tidal wind is important for study of the in situ developing processes in the lower thermosphere determining atmosphere-ionosphere dynamical coupling as well as for revealing their possible dynamical coupling with lower atmosphere. Acknowledgements: This work has been supported by Shota Rustaveli National Science Foundation grant No 31/81 and the Shota Rustaveli National Science Foundation grant No FR/51/6-300/14.

  4. p16/CDKN2 and CDK4 gene mutations in sporadic melanoma development and progression.

    PubMed

    Piccinin, S; Doglioni, C; Maestro, R; Vukosavljevic, T; Gasparotto, D; D'Orazi, C; Boiocchi, M

    1997-02-20

    The p16/CDKN2(MTS1) gene encoding for the p16 inhibitor of cyclin D/CDK4 complexes is frequently mutated and deleted in a large fraction of melanoma cell lines, and p16 germline mutations have also been observed in familial melanomas. Moreover, a CDK4 gene mutation, responsible for a functional resistance of CDK4 kinase to p16 inhibitory activity, has been described to occur in some cases of familial melanoma. These data strongly support the idea that deregulation of the CDK4/cyclin D pathway, via CDKN2 or CDK4 mutations, is of biological significance in the development of melanoma. To shed light on the role of these alterations in the development and progression of sporadic melanoma, 12 primary melanomas and 9 corresponding metastases were analyzed for CDKN2 and CDK4 gene mutations. Of the 12 primary melanomas analyzed, 4 showed the presence of mutational inactivation of the p 16 protein and 2 carried silent mutations. No metastases showed the presence of CDKN2 mutations, indicating that mutations of this cyclin-dependent kinase inhibitor is not common in the progression of sporadic melanoma. On the other hand, the absence, in the metastases, of the CDKN2 mutation detected in the corresponding primary tumors suggests that 9p21 homozygous deletion may play a major role in the metastatic spreading of this type of tumor. None of the cases analyzed showed the presence of an Arg24Cys mutation, which functionally protects CDK4 from p16 inhibition. This indicates that CDK4 mutation plays a minor role in the development and progression of sporadic melanoma.

  5. Searching for possible effects on midlatitude sporadic E layer, caused by tropospheric lightning.

    NASA Astrophysics Data System (ADS)

    Barta, Veronika; Haldoupis, Christos; Sátori, Gabriella; Buresova, Dalia

    2016-07-01

    Thunderstorms in the troposphere may affect the overlying ionosphere through electrodynamic and/or neutral atmosphere wave coupling processes. For example, it is well known that lightning discharges may impact upper atmosphere through quasi-electrostatic fields and strong electromagnetic pulses, leading to transient luminous phenomena, such as sprites and elves, along with electron heating and ionization changes in the upper D and lower E-region ionosphere that have been detected in VLF transmissions propagating in the earth-ionosphere waveguide. On the other hand, mechanical coupling between the troposphere and the ionosphere may be caused by neutral atmosphere gravity waves which are known to have their origin in massive thunderstorms. The effects of troposphere-ionosphere coupling during thunderstorms, are not yet fully established and understood, therefore there is need for more correlative studies, for example by using concurrent ionospheric and lightning observations. In the present work an effort is made to investigate a possible relationship between tropospheric lighting and sporadic E layer, which are known to dominate at bottomside ionosphere and at middle latitudes during summer. For this, a correlative analysis was undertaken using lightning data obtained with the LINET lightning detection network in Central Europe, and E region ionospheric parameters (fmin, foE, foEs, fbEs) measured with the Pruhonice (50° N, 14.5° E) DPS-4D digisonde in the summer of 2009. For direct correlation with the digisonde data, the lightning activity was quantified every 15 minutes in coincidence with the measured ionogram parameters. In the search for relation between lightning and sporadic E, the digisonde observations during lightning were also compared with those taken during a number of tropospheric storm-free days in Pruhonice. The results of this correlative study did not provide evidence of significance that favors a relationship between tropospheric lightning and

  6. Planetary Waves and Midlatitude Sporadic E Layers. Evidence For A Close Relationship

    NASA Astrophysics Data System (ADS)

    Haldoupis, C.; Pancheva, D.

    A large amplitude, 7-day period westward propagating S = 1 planetary wave has been reported from ground radar and satellite wind measurements in the mesosphere-lower thermosphere (MLT) during the second half of August and well into September, 1993. Following recent suggestions that planetary waves might play a role in the formation of midlatitude sporadic E layers (Es), we have obtained and analyzed, for the pe- riod from August 1 to September 30, 1993, the sporadic E critical frequency (foEs) time series from 8 midlatitude ionosonde stations covering a large longitudinal zone from about 58E to 157W. The analysis revealed that all 8 station foEs data showed a strong 7-day periodicity, occurring concurrently with the 7-day planetary wave re- ported elsewhere. Using independent methods for the analysis of the foEs time se- ries, we computed identical estimates for the propagation direction, zonal wavenum- ber and phase velocity of the 7-day wave which are in agreement with those reported from radar and satellite neutral wind MLT measurements. The present findings pro- vide the first direct evidence, proving that planetary waves play an important role in the physics of midlatitude sporadic E region layers. In addition, our results include an important implication, that the Es parameters measured routinely and rather reliably with a dense global network of digital ionosondes, as well as the enormous ionogram data bases existing in World Data Centers, may be used as an alternative means of studying large scale neutral atmospheric dynamics in the MLT region.

  7. Planetary waves and midlatitude sporadic E layers: Strong experimental evidence for a close relationship

    NASA Astrophysics Data System (ADS)

    Haldoupis, Christos; Pancheva, Dora

    2002-06-01

    A large-amplitude, 7-day period westward propagating S = 1 planetary wave has been reported from ground radar and satellite wind measurements in the mesosphere lower thermosphere (MLT) during the second half of August and well into September 1993. Following recent suggestions that planetary waves might play a role in the formation of midlatitude sporadic E layers (Es), we have obtained and analyzed, for the period from August 1 to September 30, 1993, the sporadic E critical frequency (foEs) time series from eight midlatitude ionosonde stations covering a large longitudinal zone from ~58°E to 157°W. The analysis revealed that all eight station foEs data showed a strong 7-day periodicity, occurring concurrently with the 7-day planetary wave reported elsewhere. Using independent methods for the analysis of the foEs time series, we computed identical estimates for the propagation direction, zonal wave number, and phase velocity of the 7-day wave, which are in agreement with those reported from radar and satellite neutral wind MLT measurements. The present findings provide the first direct evidence, proving that planetary waves play an important role in the physics of midlatitude sporadic E region layers. In addition, our results include an important implication, that the Es parameters measured routinely and rather reliably with a dense global network of digital ionosondes, as well as the enormous ionogram databases existing in World Data Centers, may be used as an alternative means of studying large-scale neutral atmospheric dynamics in the MLT region.

  8. Sporadic bilateral adrenal medullary hyperplasia: apparent false positive MIBG scan and expected MRI findings.

    PubMed

    Yung, B C; Loke, T K; Tse, T W; Tsang, M W; Chan, J C

    2000-10-01

    Adrenal medullary hyperplasia is a rare cause of clinical symptoms and biochemical findings identical to pheochromocytoma occurring mostly in multiple endocrine neoplasia patients. The scenario of positive MIBG scan, but no focal lesion found on CT and MRI led to diagnostic and management difficulties. Like pheochromocytoma, surgical excision can lead to clinical and biochemical recovery. We report this unusual case of sporadic bilateral adrenal medullary hyperplasia, with hypertension and biochemical abnormalities alleviated after surgical adrenalectomy. Based on T2 values reported in literature, high signal focal lesions may not appear on T2-weighted MRI images until development of frank pheochromocytoma. MIBG scan remains the most sensitive imaging modality for this condition.

  9. Hereditary and Sporadic Papillary Renal Carcinomas with c-met Mutations Share a Distinct Morphological Phenotype

    PubMed Central

    Lubensky, Irina A.; Schmidt, Laura; Zhuang, Zhengping; Weirich, Gregor; Pack, Svetlana; Zambrano, Norman; Walther, McClellan M.; Choyke, Peter; Linehan, W. Marston; Zbar, Berton

    1999-01-01

    Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described. We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 patients from 6 hereditary papillary renal cell carcinoma families with germline c-met mutations and 6 papillary renal cell carcinomas with c-met mutations from 5 patients with no family history of renal tumors. Twenty-five sporadic renal tumors with prominent papillary architecture and without somatic c-met mutations were evaluated for comparison. All papillary renal cell carcinomas with c-met mutations were 75 to 100% papillary/tubulopapillary in architecture and showed chromophil basophilic, papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1–2 was seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8 patients. Seventeen patients had multiple papillary adenomas and microscopic papillary lesions in the surrounding renal parenchyma. Clear cells with intracytoplasmic lipid and glycogen were focally present in tumors of 94% papillary renal cell carcinoma patients. Clear cells of papillary renal cell carcinoma had small basophilic nuclei, and clear cell areas lacked a fine vascular network characteristic of conventional (clear) cell renal cell carcinoma. We conclude that papillary renal cell carcinoma patients with c-met mutations develop multiple, bilateral, papillary macroscopic and microscopic renal lesions. Renal tumors with c-met genotype show a distinctive papillary renal cell carcinoma type 1 phenotype and are genetically and histologically different from renal tumors seen in other hereditary renal syndromes and most sporadic

  10. Psychiatric presentation of sporadic Creutzfeldt-Jakob disease: a challenge to current diagnostic criteria.

    PubMed

    Ali, Rehiana; Baborie, Atik; Larner, Andrew J; White, Richard

    2013-01-01

    Pathological diagnosis remains the gold standard for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), but being able to differentiate between CJD and non-prion diseases clinically is important because many of the non-prion, rapidly progressive dementias are treatable. Diagnostic criteria need both high sensitivity and specificity while remaining applicable to clinical practice. Despite extensive updates to the clinical criteria for sCJD, there remains a heavy emphasis on neurological signs. We describe a psychiatric presentation of sCJD that did not fulfill the diagnostic criteria until very late in a prolonged disease course and required biopsy for diagnosis.

  11. Sporadic Intra-Abdominal Desmoid: A Rare Presentation as a Hepatic Mass

    PubMed Central

    Gupta, Shahana; Ray, Udipta; Chatterjee, Souvik; Kumar, Sanjeev; Satapathy, Ayusman; Chatterjee, Shamita; Choudhury, Tamal Kanti

    2012-01-01

    We report an unusual presentation of a sporadic intra-abdominal desmoid tumour, possibly arising from the diaphragm, masquerading as a hepatic mass in a young female without any history of surgery or trauma. Histopathology ruled out a hepatic origin of the tumour as was inferred from pre- and intraoperative evaluation. Immunohistochemistry showed positivity of lesional fibroblastic cells for β-catenin and negativity for CD34, CD117, EMA, SMA, desmin, vimentin, cytokeratin, and ALK1 thereby confirming the diagnosis of a desmoid tumour. There exist only a few reports in the literature on desmoids related to the diaphragm, but only one on a diaphragmatic desmoid that is possibly primary. PMID:23091764

  12. Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning

    SciTech Connect

    Takahashi, Hirohide; Snow, B.J.; Bhatt, M.H.; Peppard, R.; Eisen, A.; Calne, D.B. )

    1993-10-23

    Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, the authors did positron emission tomography with 6-fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. They found a significant progressive fall in 6-fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis, and, perhaps, etiology.

  13. Expression of RUNX3 and β-catenin in the carcinogenesis of sporadic colorectal tubular adenoma.

    PubMed

    Wang, Linna; Li, Dan; Liu, Yang; Wang, Yuan; Cui, Jinfeng; Cui, Airong; Wu, Wenxin

    2014-06-01

    The aim of this study is to investigate the possible roles of runt-related transcription factor 3 (RUNX3) and β-catenin in the carcinogenesis of sporadic colorectal tubular adenomas. The expression of the RUNX3 and β-catenin proteins was evaluated by immunohistochemistry in 23 normal colorectal mucosa (NCM), 81 sporadic colorectal tubular adenomas with different dysplasias (SCTA-D) (mild n=33, moderate n=23, and severe n=25 dysplasia), and 48 sporadic colorectal tubular adenomas with cancerous changes (SCTA-Ca). RUNX3 methylation was assessed by methylation-specific polymerase chain reaction (MSP), combined with laser capture microdissection (LCM), in 17 NCM, 41 SCTA-D (mild n=15, moderate n=12, and severe n=14 dysplasia), and 17 SCTA-Ca tissues. Compared to NCM (82.6 %), RUNX3 in SCTA-D (54.3 %) and SCTA-Ca (27.1 %) was significantly downregulated (P<0.05). In NCM, SCTA-D, and SCTA-Ca, the incidence of positive expression for β-catenin was 13.0, 60.5, and 79.2 %, respectively. A statistically significant difference was observed (P<0.05). RUNX3 levels were markedly higher in adenoma with mild dysplasia (75.8 %) and moderate dysplasia (60.9 %) than in adenoma with severe dysplasia (20.0 %) (both with P<0.05). Likewise, the expression of β-catenin in severe dysplasia adenoma was 84.0 %, which was significantly higher than that in mild dysplasia adenoma (39.4 %). An inverse correlation was found between the protein expression of RUNX3 and β-catenin in SCTA-D and SCTA-Ca (P<0.05). MSP results showed that RUNX3 methylation in NCM, SCTA-D, and SCTA-Ca was 5.9, 17.1, and 41.2 %, respectively, with a statistically significant difference between NCM and SCTA-Ca (P<0.05). However, no significant difference of RUNX3 methylation was observed among different dysplasia groups. RUNX3 and β-catenin play important roles in the carcinogenesis of sporadic colorectal tubular adenomas. In addition, hypermethylation of RUNX3 can downregulate its expression.

  14. First description of a sporadic breast cancer in a woman with BRCA1 germline mutation

    PubMed Central

    Curtit, Elsa; Benhamo, Vanessa; Gruel, Nadège; Popova, Tatiana; Manie, Elodie; Cottu, Paul; Mariani, Odette; Stoppa-Lyonnet, Dominique; Pivot, Xavier; Stern, Marc-Henri; Vincent-Salomon, Anne

    2015-01-01

    We describe the case of a woman carrying a germline pathogenic BRCA1 mutation diagnosed with a breast cancer overexpressing HER2. Clinical presentation of the tumor, HER2-positivity, genomic profile and loss of the mutated BRCA1 allele in tumor evidence that BRCA1 is not inactivated in this breast cancer. It represents the first biological demonstration for the existence of a sporadic HER2-positive breast cancer independent from BRCA loss of function in a woman carrier of a deleterious BRCA1 mutation. In a context where targeted therapies based on BRCA loss of function in the tumor are developed, such case could have direct implications. PMID:26426992

  15. Parental origin of mutations in sporadic cases of Treacher Collins syndrome.

    PubMed

    Splendore, Alessandra; Jabs, Ethylin Wang; Félix, Têmis Maria; Passos-Bueno, Maria Rita

    2003-09-01

    In some autosomal dominant conditions, there is a correlation between new mutations and paternal age, with new mutations arising almost exclusively in the male germ line. To test this hypothesis in Treacher Collins syndrome, we analyzed 22 sporadic cases, determining the parental origin of the pathogenic mutation in 10 informative families. Mutations were found to be of both paternal and maternal origin, without a detectable parental age effect, confirming that a paternal age effect is not universal to all autosomal dominant disorders. A discussion on the parental origin of mutations and paternal age effect in other diseases is included.

  16. MEF2D and MEF2C pathways disruption in sporadic and familial ALS patients.

    PubMed

    Arosio, Alessandro; Sala, Gessica; Rodriguez-Menendez, Virginia; Grana, Denise; Gerardi, Francesca; Lunetta, Christian; Ferrarese, Carlo; Tremolizzo, Lucio

    2016-07-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuro-muscular disease characterized by motor neuron loss. MEF2D and MEF2C are members of the myocyte enhancer factor 2 family (MEF2), a group of transcription factors playing crucial roles both in muscle and in neural development and maintenance; for this reason, a possible involvement of MEF2 in ALS context has been investigated. Since the transcriptional activity of each tissue specific MEF2 isoform is conserved in different cell types, we chose to assess our parameters in an easily accessible and widely used experimental tool such as peripheral blood mononuclear cells (PBMCs) obtained from 30 sporadic ALS patients (sALS), 9 ALS patients with mutations in SOD1 gene (SOD1+) and 30 healthy controls. Gene expression analysis showed a significant up-regulation of MEF2D and MEF2C mRNA levels in both sporadic and SOD1+ ALS patients. Although protein levels were unchanged, a different pattern of distribution for MEF2D and MEF2C proteins was evidenced by immunohistochemistry in patients. A significant down-regulation of MEF2 downstream targets BDNF, KLF6 and RUFY3 was reported in both sALS and SOD1+ ALS patients, consistent with an altered MEF2 transcriptional activity. Furthermore, the potential regulatory effect of histone deacetylase 4 and 5 (HDAC4 and HDAC5) on MEF2D and MEF2C activity was also investigated. We found that MEF2D and HDAC4 colocalize in PBMC nuclei, while HDAC5 was localized in the cytoplasm. However, the unchanged HDACs localization and protein levels between sALS and controls seem to exclude their involvement in MEF2 altered function. In conclusion, our results show a systemic alteration of MEF2D and MEF2C pathways in both sporadic and SOD1+ ALS patients, underlying a possible common feature between the sporadic and the familial form of disease. Although further analyses in other neuromuscular diseases are needed to determine the specificity of changes in these pathways to ALS, measuring MEF2

  17. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

    SciTech Connect

    Alvarado, Diego; Klein, Daryl E.; Lemmon, Mark A.

    2009-09-25

    The orphan receptor tyrosine kinase ErbB2 (also known as HER2 or Neu) transforms cells when overexpressed, and it is an important therapeutic target in human cancer. Structural studies have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor. Although ErbB2 is unique among the four human ErbB receptors, here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands, yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.

  18. Kaposi Sarcoma of the Adrenal Gland Resembling Epithelioid Angiosarcoma: A Case Report

    PubMed Central

    Huwait, Hassan; Meneghetti, Adam; Nielsen, Torsten O.

    2011-01-01

    Patients with human immunodeficiency virus infection are known to have increased risk of various neoplasms, including Kaposi sarcoma, which classically involves the skin and mucosal locations. The anaplastic variant of Kaposi sarcoma is rare and poorly documented in the literature. It is characterised clinically by a more aggressive behaviour and increased metastatic potential, and histologically by increased cellularity, mitotic rate, and rarely by epithelioid angiosarcoma-like morphology. We report herein a 64-year-old man with a long-standing history of human immunodeficiency virus infection who developed a right adrenal tumor with a high-grade anaplastic angiosarcoma-like morphology. Immunohistochemistry for human herpes virus-8 was strongly positive in the tumor cells. To the best of our knowledge, this is the first report of an anaplastic Kaposi sarcoma in the adrenal gland. PMID:21845069

  19. Gene expression signature discriminates sporadic from post-radiotherapy-induced thyroid tumors

    PubMed Central

    Ory, Catherine; Ugolin, Nicolas; Levalois, Céline; Lacroix, Ludovic; Caillou, Bernard; Bidart, Jean-Michel; Schlumberger, Martin; Diallo, Ibrahima; de Vathaire, Florent; Hofman, Paul; Santini, José; Malfoy, Bernard; Chevillard, Sylvie

    2011-01-01

    Both external and internal exposure to ionizing radiation are strong risk factors for the development of thyroid tumors. Until now, the diagnosis of radiation-induced thyroid tumors has been deduced from a network of arguments taken together with the individual history of radiation exposure. Neither the histological features nor the genetic alterations observed in these tumors have been shown to be specific fingerprints of an exposure to radiation. The aim of our work is to define ionizing radiation-related molecular specificities in a series of secondary thyroid tumors developed in the radiation field of patients treated by radiotherapy. To identify molecular markers that could represent a radiation-induction signature, we compared 25K microarray transcriptome profiles of a learning set of 28 thyroid tumors, which comprised 14 follicular thyroid adenomas (FTA) and 14 papillary thyroid carcinomas (PTC), either sporadic or consecutive to external radiotherapy in childhood. We identified a signature composed of 322 genes which discriminates radiation-induced tumors (FTA and PTC) from their sporadic counterparts. The robustness of this signature was further confirmed by blind case-by-case classification of an independent set of 29 tumors (16 FTA and 13 PTC). After the histology code break by the clinicians, 26/29 tumors were well classified regarding tumor etiology, 1 was undetermined, and 2 were misclassified. Our results help shed light on radiation-induced thyroid carcinogenesis, since specific molecular pathways are deregulated in radiation-induced tumors. PMID:21148326

  20. DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy

    PubMed Central

    Abath, Osorio; Martins, Cristiane de Araújo; Carvalho, Mary; Chadi, Gerson; Seitz, Katia Werneck; Oliveira, Acary Souza Bulle; Reed, Umbertina Conti; Laporte, Jocelyn; Zanoteli, Edmar

    2015-01-01

    Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes of inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases. PMID:26273216

  1. Genetic Counseling Dilemmas for a Patient with Sporadic Amyotrophic Lateral Sclerosis, Frontotemporal Degeneration & Parkinson's Disease.

    PubMed

    Mantero, Vittorio; Tarlarini, Claudia; Aliprandi, Angelo; Lauria, Giuseppe; Rigamonti, Andrea; Abate, Lucia; Origone, Paola; Mandich, Paola; Penco, Silvana; Salmaggi, Andrea

    2017-03-01

    Amyotrophic lateral sclerosis (ALS), frontotemporal degeneration and Parkinson's disease may be different expressions of the same neurodegenerative disease. However, association between ALS and parkinsonism-dementia complex (ALS-PDC) has only rarely been reported apart from the cluster detected in Guam. We report a patient presenting with ALS-PDC in whom pathological mutations/expansions were investigated. No other family members were reported to have any symptoms of a neurological condition. Our case demonstrates that ALS-PDC can occur as a sporadic disorder, even though the coexistence of the three clinical features in one patient suggests a single underlying genetic cause. It is known that genetic testing should be preferentially offered to patients with ALS who have affected first or second-degree relatives. However, this case illustrates the importance of genetic counseling for family members of patients with sporadic ALC-PDC in order to provide education on the low recurrence risk. Here, we dicuss the ethical, psychological and practical consequences for patients and their relatives.

  2. Metabolic Risk Factors of Sporadic Alzheimer’s Disease: Implications in the Pathology, Pathogenesis and Treatment

    PubMed Central

    Chakrabarti, Sasanka; Khemka, Vineet Kumar; Banerjee, Anindita; Chatterjee, Gargi; Ganguly, Anirban; Biswas, Atanu

    2015-01-01

    Alzheimer’s disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, pro-inflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors. PMID:26236550

  3. Genetic and epigenetic alteration of the NF2 gene in sporadic meningiomas.

    PubMed

    Lomas, Jesus; Bello, M Josefa; Arjona, Dolores; Alonso, M Eva; Martinez-Glez, Victor; Lopez-Marin, Isabel; Amiñoso, Cinthia; de Campos, Jose M; Isla, Alberto; Vaquero, Jesus; Rey, Juan A

    2005-03-01

    The role of the NF2 gene in the development of meningiomas has recently been documented; inactivating mutations plus allelic loss at 22q, the site of this gene (at 22q12), have been identified in both sporadic and neurofibromatosis type 2-associated tumors. Although epigenetic inactivation through aberrant CpG island methylation of the NF2 5' flanking region has been documented in schwannoma (another NF2-associated neoplasm), data on participation of this epigenetic modification in meningiomas are not yet widely available. Using methylation-specific PCR (MSP) plus sequencing, we assessed the presence of aberrant promoter NF2 methylation in a series of 88 meningiomas (61 grade I, 24 grade II, and 3 grade III), in which the allelic constitution at 22q and the NF2 mutational status also were determined by RFLP/microsatellite and PCR-SSCP analyses. Chromosome 22 allelic loss, NF2 gene mutation, and aberrant NF2 promoter methylation were detected in 49%, 24%, and 26% of cases, respectively. Aberrant NF2 methylation with loss of heterozygosity (LOH) at 22q was found in five cases, and aberrant methylation with NF2 mutation in another; LOH 22q and the mutation were found in 16 samples. The aberrant methylation of the NF2 gene also was the sole alteration in 15 samples, most of which were from grade I tumors. These results indicate that aberrant NF2 hypermethylation may participate in the development of a significant proportion of sporadic meningiomas, primarily those of grade I.

  4. Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing

    PubMed Central

    Xu, Jing; Li, Zhongshan; Ren, Xianguo; Dong, Ming; Li, Jinxin; Shi, Xingjuan; Zhang, Yu; Xie, Wei; Sun, Zhongsheng; Liu, Xiangdong; Dai, Qiming

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with high heterogeneity. Limited knowledge concerning the genetic background of nearly 40% HCM cases indicates there is a clear need for further investigation to explore the genetic pathogenesis of the disease. In this study, we undertook a whole exome sequencing (WES) approach to identify novel candidate genes and mutations associated with HCM. The cohort consisted of 74 unrelated patients with sporadic HCM (sHCM) previously determined to be negative for mutations in eight sarcomere genes. The results showed that 7 of 74 patients (9.5%) had damaging mutations in 43 known HCM disease genes. Furthermore, after analysis combining the Transmission and De novo Association (TADA) program and the ToppGene program, 10 putative genes gained priority. A thorough review of public databases and related literature revealed that there is strong supporting evidence for most of the genes playing roles in various aspects of heart development. Findings from recent studies suggest that the putative and known disease genes converge on three functional pathways: sarcomere function, calcium signaling and metabolism pathway. This study illustrates the benefit of WES, in combination with rare variant analysis tools, in providing valuable insight into the genetic etiology of a heterogeneous sporadic disease. PMID:26573135

  5. The ‘Pokemon’ (ZBTB7) Gene: No Evidence of Association with Sporadic Breast Cancer

    PubMed Central

    Salas, Antonio; Vega, Ana; Milne, Roger L.; García-Magariños, Manuel; Ruibal, Álvaro; Benítez, Javier; Carracedo, Ángel

    2008-01-01

    It has been proposed that the excess of familiar risk associated with breast cancer could be explained by the cumulative effect of multiple weakly predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon, has recently been identified as a critical factor in oncogenesis. This protein is encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in ZBTB7 are associated with breast cancer risk in a sample of cases and controls collected in hospitals from North and Central Spanish patients. We genotyped 15 SNPs in ZBTB7, including the flanking regions, with an average coverage of 1 SNP/2.4 Kb, in 360 sporadic breast cancer cases and 402 controls. Comparison of allele, genotype and haplotype frequencies between cases and controls did not reveal associations using Pearson’s chi-square test and a permutation procedure to correct for multiple test. In this, the first study of the ZBTB7 gene in relation to, sporadic breast cancer, we found no evidence of an association. PMID:21892298

  6. Risk Factors for Sporadic Pancreatic Neuroendocrine Tumors: A Case-Control Study

    PubMed Central

    Ben, Qiwen; Zhong, Jie; Fei, Jian; Chen, Haitao; Yv, Lifen; Tan, Jihong; Yuan, Yaozong

    2016-01-01

    The current study examined risk factors for sporadic pancreatic neuroendocrine tumors (PNETs), including smoking, alcohol use, first-degree family history of any cancer (FHC), and diabetes in the Han Chinese ethnic group. In this clinic-based case-control analysis on 385 patients with sporadic PNETs and 614 age- and sex-matched controls, we interviewed subjects using a specific questionnaire on demographics and potential risk factors. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (AORs). No significant differences were found between patients and controls in terms of demographic variables. Most of the patients with PNETs had well-differentiated PNETs (G1, 62.9%) and non-advanced European Neuroendocrine Tumor Society (ENETS) stage (stage I or II, 83.9%). Ever/heavy smoking, a history of diabetes and a first-degree FHC were independent risk factors for non-functional PNETs. Only heavy drinking was found to be an independent risk factor for functional PNETs (AOR = 1.87; 95% confidence interval [CI], 1.01–3.51). Ever/heavy smoking was also associated with advanced ENETS staging (stage III or IV) at the time of diagnosis. This study identified first-degree FHC, ever/heavy smoking, and diabetes as risk factors for non-functional PNETs, while heavy drinking as a risk factor for functional PNETs. PMID:27782199

  7. Early detection of sporadic pancreatic cancer: strategic map for innovation--a white paper.

    PubMed

    Kenner, Barbara J; Chari, Suresh T; Cleeter, Deborah F; Go, Vay Liang W

    2015-07-01

    Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer.

  8. Partial Nephrectomy for a Massive Sporadic Renal Angiomyolipoma: Case Report and Review of the Literature

    PubMed Central

    Klein, Molly; Murugan, Paari; Weight, Christopher J.

    2016-01-01

    Introduction. Angiomyolipomas are the most common benign tumor of the kidney, associated with Tuberous Sclerosis in 20% of cases and arising sporadically in 80% of cases. Renal angiomyolipomas are neoplasms of mesenchymal origin with varying proportions of vasculature, smooth muscle spindle cells, and adipocytes, making management of such neoplasms a challenging endeavor. Possible management options include partial or radical nephrectomy and segmental renal artery embolization. Case Presentation. A 61-year-old woman admitted for a large retroperitoneal hemorrhage was discovered to have a giant, sporadic, 3818.3 g, 30.0 × 26.5 × 18.0 cm left perinephric angiomyolipoma. Given her hemodynamic instability upon presentation, she underwent segmental arterial embolization, followed by an open left partial nephrectomy. Ten-month follow-up revealed no noticeable loss of renal function. Discussion. Literature review revealed occasional renal angiomyolipomas of comparable size, with all angiomyolipomas larger than this requiring treatment with radical nephrectomy. Conclusion. We show that nephron-sparing surgery may be considered in the treatment of even the largest of renal angiomyolipomas. PMID:28070443

  9. De Novo Truncating FUS Gene Mutation as a Cause of Sporadic Amyotrophic Lateral Sclerosis

    PubMed Central

    DeJesus-Hernandez, Mariely; Kocerha, Jannet; Finch, NiCole; Crook, Richard; Baker, Matt; Desaro, Pamela; Johnston, Amelia; Rutherford, Nicola; Wojtas, Aleksandra; Kennelly, Kathleen; Wszolek, Zbigniew K.; Graff-Radford, Neill; Boylan, Kevin; Rademakers, Rosa

    2010-01-01

    Mutations in the gene encoding fused in sarcoma (FUS) were recently identified as a novel cause of amyotrophic lateral sclerosis (ALS), emphasizing the genetic heterogeneity of ALS. We sequenced the genes encoding superoxide dismutase (SOD1), TAR DNA-binding protein 43 (TARDBP) and FUS in 99 sporadic and 17 familial ALS patients ascertained at Mayo Clinic. We identified two novel mutations in FUS in two out of 99 (2.0%) sporadic ALS patients and established the de novo occurrence of one FUS mutation. In familial patients, we identified three (17.6%) SOD1 mutations, while FUS and TARDBP mutations were excluded. The de novo FUS mutation (g.10747A>G; IVS13-2A>G) affects the splice-acceptor site of FUS intron 13 and was shown to induce skipping of FUS exon 14 leading to the C-terminal truncation of FUS (p.G466VfsX14). Subcellular localization studies showed a dramatic increase in the cytoplasmic localization of FUS and a reduction of normal nuclear expression in cells transfected with truncated compared to wild-type FUS. We further identified a novel in-frame insertion/deletion mutation in FUS exon 12 (p.S402 P411delinsGGGG) which is predicted to expand a conserved poly-glycine motif. Our findings extend the mutation spectrum in FUS leading to ALS and describe the first de novo mutation in FUS. PMID:20232451

  10. Apolipoprotein E and lipid homeostasis in the etiology and treatment of sporadic Alzheimer's disease.

    PubMed

    Poirier, Judes; Miron, Justin; Picard, Cynthia; Gormley, Patrick; Théroux, Louise; Breitner, John; Dea, Doris

    2014-09-01

    The discovery that the apolipoprotein E (apoE) ε4 allele is genetically linked to both sporadic and familial late-onset Alzheimer's disease (AD) raises the possibility that a dysfunction of the lipid transport system could seriously affect lipid homeostasis in the brain of AD subjects. The presence of the ε4 allele has been associated with lower levels of apoE in both serum and brain tissues of normal and AD subjects. In an attempt to reverse the apoE deficit in AD, we identified and characterized several apoE inducer agents using a low-throughput in vitro screening assay. The most promising of these compounds is called probucol. Administration of probucol, an old cholesterol-lowering drug, in a pilot trial in mild-to-moderate sporadic AD led to a significant increase in cerebrospinal fluid (CSF) apoE levels and a decrease in CSF in both phosphorylated tau 181 and beta-amyloid 1-42 concentrations without significant modifications of lipid hydroperoxide levels.

  11. Breast-feeding decreases the risk of sporadic salmonellosis among infants in FoodNet sites.

    PubMed

    Rowe, Samantha Y; Rocourt, Jocelyne R; Shiferaw, Beletshachew; Kassenborg, Heidi D; Segler, Suzanne D; Marcus, Ruthanne; Daily, Pamala J; Hardnett, Felicia P; Slutsker, Laurence

    2004-04-15

    Among the population of the Foodborne Diseases Active Surveillance Network (FoodNet) surveillance areas ("FoodNet sites") in 1996, children under 12 months of age had the highest incidence of sporadic salmonellosis. We conducted a case-control study in 5 FoodNet sites to identify risk factors for sporadic infant salmonellosis. A case patient was a child under 12 months of age with a laboratory-confirmed, nontyphoidal serogroup B or D Salmonella infection. Twenty-two case patients were matched with 39 control subjects by age and either telephone exchange or vital record birth list. In a multivariate analysis, case patients were more likely to have a liquid diet containing no breast milk than a liquid diet containing only breast milk (matched odds ratio, 44.5; P=.04). Case-patients were more likely to reside in a household where a member had diarrhea (matched odds ratio, 13.2; P=.01). To decrease their infants' risk of salmonellosis, mothers should be encouraged to breast-feed their infants. Caretakers of infants should learn about salmonellosis, hand washing, and safe preparation of formula and solid food.

  12. Patterns of Weakness, Classification of Motor Neuron Disease & Clinical Diagnosis of Sporadic ALS

    PubMed Central

    Statland, Jeffrey M.; Barohn, Richard J.; McVey, April L.; Katz, Jonathan; Dimachkie, Mazen M.

    2015-01-01

    Synopsis When approaching the patient with suspected motor neuron disease (MND) the pattern of weakness on exam helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing, in the absence of other abnormalities on neuroimaging or serological testing. MNDs exist on a spectrum: from a pure lower motor neuron; to mixed upper and lower motor neuron; to a pure upper motor neuron variant in addition to regional variants restricted to the arms, legs or bulbar region. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic (~85%), which is invariably fatal. The only FDA approved treatments for ALS are riluzole, which prolongs life by about 3 months, and dextromethorphan/quinidine which provides symptomatic relief for pseudobulbar affect (inappropriate bouts of laughter or crying). Here we describe a pattern approach to identifying motor neuron disease, and clinical features of sporadic ALS. PMID:26515618

  13. Does restraining nitric oxide biosynthesis rescue from toxins-induced parkinsonism and sporadic Parkinson's disease?

    PubMed

    Gupta, Satya Prakash; Yadav, Sharawan; Singhal, Naveen Kumar; Tiwari, Manindra Nath; Mishra, Sarad Kumar; Singh, Mahendra Pratap

    2014-02-01

    Nitric oxide (NO) is an important inorganic molecule of the biological system owing to diverse physiological implications. NO is synthesised from a semi-essential amino acid L-arginine. NO biosynthesis is catalysed by a family of enzymes referred to as nitric oxide synthases (NOSs). NO is accused in many acute and chronic illnesses, which include central nervous system disorders, inflammatory diseases, reproductive impairments, cancer and cardiovascular anomalies. Owing to very unstable nature, NO gets converted into nitrite, peroxynitrite and other reactive nitrogen species that could lead to nitrosative stress in the nigrostriatal system. Nitrosative stress is widely implicated in Parkinson's disease (PD), and its beneficial and harmful effects are demonstrated in in vitro, rodent and primate models of toxins-induced parkinsonism and in the blood, cerebrospinal fluid and nigrostriatal tissues of sporadic PD patients. The current article updates the roles of NO and NOSs in sporadic PD and toxins-induced parkinsonism in rodents along with the scrutiny of how inhibitors of NOSs could open a new line of approach to moderately rescue from PD pathogenesis based on the existing literature. The article also provides a perspective concerning the lack of ample admiration to such an approach and how to minimise the underlying lacunae.

  14. Rocket/Radar Investigation of Lower Ionospheric Electrodynamics Associated with Intense Midlatitude Sporadic-E Layers

    NASA Technical Reports Server (NTRS)

    Heelis, R. A.

    1998-01-01

    Sporadic layers, which appear in the region from 100 km to 120 km are thought to be formed by convergent Pedersen drifts induced by altitude gradients in the zonal neutral wind. In this altitude region NO+ and 02+ are the major ions produced by photoionization and charge exchange of atmospheric and ionospheric species. The relative composition of atmospheric ions and meteoric ions in sporadic layers is important in determining their persistence, the time scales for formation, and the electrical conductivity of the layers. This rocket investigation will include a diagnosis of the neutral wind field and the electric field distribution. Coupled with ion composition measurements we will be able to expose the relevant formation mechanisms and the electrodynamic consequences of their existence. A rocket trajectory has been chosen to provide substantial horizontal sampling of the layer properties and knowledge of the horizontal gradients in composition and density are essential to determine the polarization electric fields that may be associated with ionospheric layers. The University of Texas at Dallas (UTD) is responsible for designing, building, and operating the ion mass spectrometers included on these rockets. The following provides a summary of the UTD accomplishments in the second year of the project as well as a description of the plans for the third year's activities. The UTD mass spectrometer acronym has been coined as PRIMS for Puerto Rico Ion Mass Spectrometer.

  15. Is PFAPA syndrome really a sporadic disorder or is it genetic?

    PubMed

    Akelma, Ahmet Zulfikar; Cizmeci, Mehmet Nevzat; Kanburoglu, Mehmet Kenan; Mete, Emin; Bozkaya, Davut; Tufan, Naile; Catal, Ferhat

    2013-08-01

    Periodic fever syndromes are a group of disorders sharing similar symptoms, characterized primarily by regularly recurring fevers. PFAPA syndrome, one of the members of this group of disorders, is a clinical entity of unknown etiology which is frequently seen in the early childhood. Currently, the pathogenesis and the genetic basis of most of the disorders in the periodic fever spectrum are known, other than that of PFAPA syndrome. Although, classically PFAPA syndrome is known as a sporadic disease, we propose that it is not sporadic. We think that PFAPA syndrome may be an inherited disease and this hypothesis is supported by the clinical mimicry of PFAPA syndrome with other periodic fever syndromes with well-known genetic transmissions, frequent occurrence of the condition in members of the same family and emergence of common genetic mutations in the periodic fever syndrome spectrum. Moreover, our clinical observation that most of the patients diagnosed with PFAPA syndrome were of the same families strongly suggest a probable genetic transmission of this disorder. We have decided to discuss this hypothesis to contribute to the literature and assist our colleagues who are dealing with this commonly overlooked and often misdiagnosed disorder.

  16. A study of the airglow and the sporadic E layers during stratospheric warming events

    NASA Astrophysics Data System (ADS)

    Mikhalev, Alexander; Ratovsky, Konstantin; Medvedev, Andrey; Medvedeva, Irina; Kurkin, Vladimir; Chernigovskaya, Marina; Kostyleva, Nadegda

    In the present work the events of disturbances of the 557.7 nm and 630 nm airglow and occurrence of sporadic E layer in middle latitudes of Asian region during sudden stratospheric warmings in December 2006 and January-February 2008 are analyzed. Ionosphere data were obtained with the DPS-4 ionosonde located in Irkutsk (52.3N, 104.3E). Airglow measurements were made by the 4-channel zenith photometer and colour CCD imager at ISTP Geophysical observatory located 130 km southwest of Irkutsk. To identify the stratospheric warming events the Berlin Meteorological University data (http://strat-www.met.fu-berlin.de) on stratospheric warming at standard isobaric levels and the atmospheric temperature height profiles measured by the Microwave Limb Sounder (MLS) aboard the EOS Aura spacecraft were used. In some cases we observed correlated diurnal variations of 557.7 nm airglow intensity and Es characteristics. The fact that the correlation between 557.7 nm and Es layer characteristics did not always happen probably can be explained by the different spatial localization of Es layer and emitting layer as well as by the features of their dynamics. During a maximal rise of 557.7 nm airglow its spatial inhomogeneity registered by CCD imager in a continuum was observed. The possible mechanisms of the airglow disturbances and occurrence of sporadic E layers during sudden stratospheric warming are discussed. The work was supported by RAS Presidium Program 16 (Part 3).

  17. Analysis of the TSC1and TSC2genes in sporadic renal cell carcinomas

    PubMed Central

    Parry, L; Maynard, J H; Patel, A; Clifford, S C; Morrissey, C; Maher, E R; Cheadle, J P; Sampson, J R

    2001-01-01

    The genetic events involved in the aetiology of non-clear-cell renal cell carcinoma (RCC) and a proportion of clear cell RCC remain to be defined. Germline mutations of the TSC1and TSC2genes cause tuberous sclerosis (TSC), a multi-system hamartoma syndrome that is also associated with RCC. We assessed 17 sporadic clear cell RCCs with a previously identified VHLmutation, 15 clear-cell RCCs without an identified VHLmutation and 15 non-clear-cell RCCs for loss of heterozygosity (LOH) at chromosomes 9q34 and 16p13.3, the chromosomal locations of TSC1and TSC2. LOH was detected in 4/9, 1/11 and 3/13 cases informative at both loci. SSCP analysis of the whole coding region of the retained allele did not reveal any cases with a detectable intragenic second somatic mutation. Furthermore, RT-PCR analysis of TSC1and TSC2on total RNA from 8 clear-cell RCC cell lines confirmed expression of both TSC genes. These data indicate that biallelic inactivation of TSC1or TSC2is not frequent in sporadic RCC and suggests that the molecular mechanisms of renal carcinogenesis in TSC are likely to be distinct. © 2001 Cancer Research Campaignhttp://www.bjcancer.com  http://www.bjcancer.com PMID:11710839

  18. Risk Factors for Sporadic Cryptosporidiosis among Immunocompetent Persons in the United States from 1999 to 2001

    PubMed Central

    Roy, Sharon L.; DeLong, Stephanie M.; Stenzel, Sara A.; Shiferaw, Beletshachew; Roberts, Jacquelin M.; Khalakdina, Asheena; Marcus, Ruthanne; Segler, Suzanne D.; Shah, Dipti D.; Thomas, Stephanie; Vugia, Duc J.; Zansky, Shelley M.; Dietz, Vance; Beach, Michael J.

    2004-01-01

    Many studies have evaluated the role of Cryptosporidium spp. in outbreaks of enteric illness, but few studies have evaluated sporadic cryptosporidiosis in the United States. To assess the risk factors for sporadic cryptosporidiosis among immunocompetent persons, a matched case-control study was conducted in seven sites of the Foodborne Diseases Active Surveillance Network (FoodNet) involving 282 persons with laboratory-identified cryptosporidiosis and 490 age-matched and geographically matched controls. Risk factors included international travel (odds ratio [OR] = 7.7; 95% confidence interval [95% CI] = 2.7 to 22.0), contact with cattle (OR = 3.5; 95% CI = 1.8 to 6.8), contact with persons >2 to 11 years of age with diarrhea (OR = 3.0; 95% CI = 1.5 to 6.2), and freshwater swimming (OR = 1.9; 95% CI = 1.049 to 3.5). Eating raw vegetables was protective (OR = 0.5; 95% CI = 0.3 to 0.7). This study underscores the need for ongoing public health education to prevent cryptosporidiosis, particularly among travelers, animal handlers, child caregivers, and swimmers, and the need for further assessment of the role of raw vegetables in cryptosporidiosis. PMID:15243043

  19. Investigation of dynamic behind the seasonal variations of Es and sporadic Na layer near the turbopause of aurora free zone

    NASA Astrophysics Data System (ADS)

    Yuan, T.; Sojka, J. J.; Criddle, N.; Cai, X.; Rice, D.

    2013-12-01

    The dearth of experimental observations, as well as dynamics study, near the turbopause (100-120 km) is the culprit for the mystery of this critical layer in the lower thermosphere. The sporadic E layer (Es) and the sporadic Na layer, occurring within this region, provide unique tracers for such topic. It is believed that the downward transporting of Es, which is full with metal ions (such as Na+), enriches the Na reservoir in the lower E region that causes the occurrence of sporadic Na layer within. In this paper, a statistic study show strong positive correlation between Es and sporadic Na layer above 100 km, measured by Utah State University Na lidar at Logan, Utah and CADI (ionosonde) at Bear Lake Observatory nearby. Both of these two turbopause features indicate strong seasonal variation with peak occurrence rate in the summer and minimum during the winter. To explain the dynamics behind the variations in the aurora free zone, HAMMONIA model produced monthly zonal wind climatology and Climatological Tidal Model of the Thermospehre (CTMT) are joining together to reproduce the hourly zonal wind variation within the turbopause, along with the temperature prediction from the two models. Using the well accepted wind shear theory of the Es formation, we conclude that such seasonal behaviors of Es and sporadic Na layer are due to large negative zonal wind shear driven by tidal wave peaking near the turbopause during summer time in the early evening.

  20. Performance of D-criteria in isolating meteor showers from the sporadic background in an optical data set

    NASA Astrophysics Data System (ADS)

    Moorhead, Althea V.

    2016-02-01

    Separating meteor showers from the sporadic meteor background is critical for the study of both showers and the sporadic complex. The linkage of meteors to meteor showers, to parent bodies, and to other meteors is done using measures of orbital similarity. These measures often take the form of so-called D-parameters and are generally paired with some cutoff value within which two orbits are considered related. The appropriate cut-off value can depend on the size of the data set (Southworth & Hawkins 1963), the sporadic contribution within the observed size range (Jopek 1995), or the inclination of the shower (Galligan 2001). If the goal is to minimize sporadic contamination of the extracted shower, the cut-off value should also reflect the strength of the shower compared to the local sporadic background. In this paper, we present a method for determining, on a per-shower basis, the orbital similarity cut-off value that corresponds to a chosen acceptable false-positive rate. This method also assists us in distinguishing which showers are significant within a set of data. We apply these methods to optical meteor observations from the NASA All-Sky and Southern Ontario Meteor Networks.

  1. Comparison of Observations of Sporadic-E Layers in the Nighttime and Daytime Mid-Latitude Ionosphere

    NASA Technical Reports Server (NTRS)

    Pfaff, R.; Freudenreich, H.; Rowland, D.; Klenzing, J.; Clemmons, J.; Larsen, M.; Kudeki, E.; Franke, S.; Urbina, J.; Bullett, T.

    2012-01-01

    A comparison of numerous rocket experiments to investigate mid-latitude sporadic-E layers is presented. Electric field and plasma density data gathered on sounding rockets launched in the presence of sporadic-E layers and QP radar echoes reveal a complex electrodynamics including both DC parameters and plasma waves detected over a large range of scales. We show both DC and wave electric fields and discuss their relationship to intense sporadic-E layers in both nighttime and daytime conditions. Where available, neutral wind observations provide the complete electrodynamic picture revealing an essential source of free energy that both sets up the layers and drives them unstable. Electric field data from the nighttime experiments reveal the presence of km-scale waves as well as well-defined packets of broadband (10's of meters to meters) irregularities. What is surprising is that in both the nighttime and daytime experiments, neither the large scale nor short scale waves appear to be distinctly organized by the sporadic-E density layer itself. The observations are discussed in the context of current theories regarding sporadic-E layer generation and quasi-periodic echoes.

  2. Post-transfusional vs. sporadic non-A, non-B chronic hepatitis. A clinico-pathological and evolutive study.

    PubMed

    Jové, J; Sánchez-Tapias, J M; Bruguera, M; Mas, A; Costa, J; Barrera, J M; Rodés, J

    1988-02-01

    The clinical, morphological and evolutive features of 60 patients with chronic hepatitis, presumably caused by non-A, non-B virus infection, have been retrospectively analyzed. In all the cases the disease began as an acute episode of viral hepatitis that was followed by persistently abnormal liver function tests. No patient had evidence of current or past hepatitis B virus infection and other known causes of chronic liver disease were excluded. Thirty patients had received blood transfusions in the recent past, five were drug addicts and the source of the infection was not identified in the remaining 25, in whom the disease was considered to be sporadic. Clinical or biochemical differences between patients with post-transfusional and sporadic non-A, non-B chronic hepatitis were not observed, but liver histology showed a higher proportion of patients with chronic persistent hepatitis in the sporadic (72%) than in the transfusional group (53%). On follow-up, sustained normalization of liver function tests was observed in 46% of the cases with sporadic hepatitis but only in 13% of the cases with post-transfusion hepatitis. These observations suggest that non-A, non-B chronic hepatitis is more severe in patients with transfusion-related infection than in sporadic cases.

  3. Sporadic salmonellosis in Lower Saxony, Germany, 2011-2013: raw ground pork consumption is associated with Salmonella Typhimurium infections and foreign travel with Salmonella Enteritidis infections.

    PubMed

    Rettenbacher-Riefler, S; Ziehm, D; Kreienbrock, L; Campe, A; Pulz, M; Dreesman, J

    2015-10-01

    To investigate risk factors for sporadic salmonellosis, for each notified case four randomly selected population controls matched for age, sex and geographical region were interviewed via self-administered questionnaire. Conditional logistic regression analysis of 285 matched pairs revealed significant associations for raw ground pork consumption [odds ratio (OR) 6·0, 95% confidence interval (CI) 1·8-20·1], taking antacids (OR 5·8, 95% CI 1·4-24·5), eating meat outside the home (OR 5·7, 95% CI 2·2-14·6) and daily changing or cleaning of dishcloth (OR 2·1, 95% CI 1·2-3·9). Animal contact and ice cream consumption were negatively associated with salmonellosis (OR 0·5, 95% CI 0·2-1 and OR 0·3, 95% CI 0·1-0·6, respectively). S. Typhimurium infections were significantly associated with raw ground pork consumption (OR 16·7, 95% CI 1·4-194·4) and S. Enteritidis infections with having travelled abroad (OR 9·7, 95% CI 2·0-47·3). Raw egg consumption was not a risk factor, substantiating the success of recently implemented national control programmes in the poultry industry. Unexpectedly, hygienic behaviour was more frequently reported by cases, probably because they overestimated their hygiene precautions retrospectively. Although animal contact might enhance human immunocompetence, underreporting of salmonellosis by pet owners could have occurred. Eating raw pork products is the major risk factor for sporadic human S. Typhimurium infections in Lower Saxony.

  4. Multifocal pyogranulomatous osteomyelitis resembling chronic recurrent multifocal osteomyelitis in a lemur.

    PubMed

    Backues, K A; Hoover, J P; Bahr, R J; Confer, A W; Chalman, J A; Larry, M L

    2001-01-15

    Chronic recurrent multifocal osteomyelitis is a rare inflammatory bone disease of children and adolescents that is characterized by localized swelling and pain in the clavicles and long bones of the limbs. Diagnosis of chronic recurrent multifocal osteomyelitis is made from clinical signs, characteristic radiographic and histopathologic findings, and negative results of microbial cultures. Treatment of chronic recurrent multifocal osteomyelitis in humans includes administration of nonsteroidal anti-inflammatory drugs or immune modulators, which may be effective in lemurs.

  5. Aberrant Mucin Assembly in Mice Causes Endoplasmic Reticulum Stress and Spontaneous Inflammation Resembling Ulcerative Colitis

    PubMed Central

    Price, Gareth R; Tauro, Sharyn B; Taupin, Douglas; Thornton, David J; Png, Chin Wen; Crockford, Tanya L; Cornall, Richard J; Adams, Rachel; Kato, Masato; Nelms, Keats A; Hong, Nancy A; Florin, Timothy H. J; Goodnow, Christopher C; McGuckin, Michael A

    2008-01-01

    Background MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterised the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis. Methods and Findings By murine N-ethyl-N-nitrosourea mutagenesis we identified two distinct noncomplementing missense mutations in Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both strains developed mild spontaneous distal intestinal inflammation by 6 wk (histological colitis scores versus wild-type mice, p < 0.01) and chronic diarrhoea. Monitoring over 300 mice of each strain demonstrated that 25% and 40% of each strain, respectively, developed severe clinical signs of colitis by age 1 y. Mutant mice showed aberrant Muc2 biosynthesis, less stored mucin in goblet cells, a diminished mucus barrier, and increased susceptibility to colitis induced by a luminal toxin. Enhanced local production of IL-1β, TNF-α, and IFN-γ was seen in the distal colon, and intestinal permeability increased 2-fold. The number of leukocytes within mesenteric lymph nodes increased 5-fold and leukocytes cultured in vitro produced more Th1 and Th2 cytokines (IFN-γ, TNF-α, and IL-13). This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis, and wound repair. Expression of mutated Muc2 oligomerisation domains in vitro demonstrated that aberrant Muc2 oligomerisation underlies the ER stress. In human ulcerative colitis we demonstrate similar

  6. Martian alkaline basites chemically resemble basic rocks of the Lovozero alkaline massif, Kola peninsula

    NASA Astrophysics Data System (ADS)

    Kochemasov, G.

    " (syenite, granite) for Mars [5]. Actually the martian missions successively discovered andesite, dacite, low-Fe highlands. Now "Spirit" has found on a small outlier of highlands -Columbia Hills -a batch of thinly layered gently dipping light rocks that surely are not impact melts as at very short distance there is a sharp transition from light Fe-poor to ultrabasic rocks (on opposite slopes of this small hill) [6]. This layered sequence of more or less altered and weathered rocks resembles differentiated sequences of Lovozero and other alkaline and UB-alkaline massifs of Kola Peninsula (though fresh and much richer in alkalis). Here we compare compositions of alkaline basic rocks of Columbia Hills (dyke or sill [4]) with that of basic volcanics and a later dyke at Lovozero. 5 analyses in wt.%: 1-Backstay (tra1 chybasalt) & 2-Irvine (basalt) of CH, 3-augiteporphyrite, 4-essexite-porphyrite, 5- alkali- lamprophyre dyke of Lovozero. SiO2 -49.9, 47.7, 45.78, 48.09, 41.57; TiO2 - 0.93, 1.07, 7.80, 2.35, 2.92; Al2 O3 -13.2; 10.8, 8.08; 13.74; 11.77; Fe2 O3 -3.40, 7.79 (4.99), 5.90, 6.00, 4.53; FeO -10.6, 12.5 (15.0), 8.65, 7.60, 8.28; MnO -0.25, 0.37, 0.12, 0.17, 0.28; MgO -8.36, 10.8, 7.61, 7.19, 10.59; CaO -6.09, 6.12, 10.73, 8.77, 11.24; Na2 O -4.02, 2.72, 2.80, 2.84, 3.63; K2 O -1.02, 0.69, 1.97, 2.09, 1.38. Compositional similarities between basites occurring in alkaline conditions on both planets can be found. References: [1] Kochemasov G.G. (1999) Theorems of wave planetary tectonics // Geophys. Res. Abstr., v. 1, # 3, 700; [2] Gellert R. et al. (2006) JGR Planets, v. 111, #E2, EO2505; [3] Squyres S.W. et al. (2006) JGR Planets, v.111, #E2, EO2511; [4] McSween H.Y. et al. (2006) JGR Planets, submitted ; [5] Kochemasov G. G. (1995) Golombek M.P., Edgett K.S., Rice J.W. Jr. (Eds). Mars Pathfinder Landing Site Workshop II: Characteristics of the Ares Vallis Region and Field trips to the Channeled Scabland, Washington. LPI Tech. Rpt. 95-01. Pt.1.LPI, Houston, 1995, 63 pp.; [6

  7. Generational Status, Neighborhood Context, and Mother-Child Resemblance in Dietary Quality in Mexican-origin Families

    PubMed Central

    Van Hook, Jennifer

    2016-01-01

    Children of immigrants in the United States often grow up in very different nutrition environments than their parents. As a result, parent-child concordance in diet may be particularly weak in immigrant families. Yet, little is known about parent-child dietary resemblance in immigrant families and how local contexts shape it. This study uses data from the 1999/2000–2009/2010 Continuous National Health and Nutrition Examination Survey to examine mother-child resemblance in dietary quality in Mexican-origin families in the United States. We investigate how immigrant generational status and neighborhood context shape the association between mothers’ and children’s dietary quality. We find that mother-child resemblance in dietary quality is weaker for first-generation children relative to third-generation children. However, residence in an immigrant enclave strengthens the mother-child association in dietary quality for first-generation children. Findings offer a unique within-family perspective of immigrant health. Results suggest that the healthy eating advantage of Mexican immigrant mothers may not be sustained across family generations and that Mexican immigrant mothers may face unique challenges in promoting healthy eating among their children. PMID:26773704

  8. Generational status, neighborhood context, and mother-child resemblance in dietary quality in Mexican-origin families.

    PubMed

    Dondero, Molly; Van Hook, Jennifer

    2016-02-01

    Children of immigrants in the United States often grow up in very different nutrition environments than their parents. As a result, parent-child concordance in diet may be particularly weak in immigrant families. Yet, little is known about parent-child dietary resemblance in immigrant families and how local contexts shape it. This study uses data from the 1999/2000-2009/2010 Continuous National Health and Nutrition Examination Survey to examine mother-child resemblance in dietary quality in Mexican-origin families in the United States. We investigate how immigrant generational status and neighborhood context shape the association between mothers' and children's dietary quality. We find that mother-child resemblance in dietary quality is weaker for first-generation children relative to third-generation children. However, residence in an immigrant enclave strengthens the mother-child association in dietary quality for first-generation children. Findings offer a unique within-family perspective of immigrant health. Results suggest that the healthy eating advantage of Mexican immigrant mothers may not be sustained across family generations and that Mexican immigrant mothers may face unique challenges in promoting healthy eating among their children.

  9. A preliminary study of the whole-genome expression profile of sporadic and monogenic early-onset Alzheimer's disease.

    PubMed

    Antonell, Anna; Lladó, Albert; Altirriba, Jordi; Botta-Orfila, Teresa; Balasa, Mircea; Fernández, Manel; Ferrer, Isidre; Sánchez-Valle, Raquel; Molinuevo, José Luis

    2013-07-01

    Alzheimer's disease (AD) is the most common neurodegenerative dementia. Approximately 10% of cases present at an age of onset before 65 years old, which in turn can be monogenic familial AD (FAD) or sporadic early-onset AD (sEOAD). Mutations in PSEN1, PSEN2, and APP genes have been linked with FAD. The aim of our study is to describe the brain whole-genome RNA expression profile of the posterior cingulate area in sEOAD and FAD caused by PSEN1 mutations (FAD-PSEN1). Fourteen patients (7 sEOAD and 7 FAD-PSEN1) and 7 neurologically healthy control subjects were selected and whole-genome expression was measured using Affymetrix Human Gene 1.1 microarrays. We identified statistically significant expression changes in sEOAD and FAD-PSEN1 brains with respect to control subjects (3183 and 3350 differentially expressed genes [DEG] respectively, false discovery rate-corrected p < 0.05). Of them, 1916 DEG were common between the 2 comparisons. We did not identify DEG between sEOAD and FAD-PSEN1. Microarray data were validated through real-time quantitative polymerase chain reaction. In silico analysis of DEG revealed an alteration in biological pathways related to intracellular signaling pathways (particularly calcium signaling), neuroactive ligand-receptor interactions, axon guidance, and long-term potentiation in both groups of patients. In conclusion, the altered biological final pathways in sEOAD and FAD-PSEN1 are mainly related with cell signaling cascades, synaptic plasticity, and learning and memory processes. We hypothesize that these 2 groups of early-onset AD with distinct etiologies and likely different could present a neurodegenerative process with potential different pathways that might converge in a common and similar final stage of the disease.

  10. Validation of 14-3-3 Protein as a Marker in Sporadic Creutzfeldt-Jakob Disease Diagnostic.

    PubMed

    Schmitz, Matthias; Ebert, Elisabeth; Stoeck, Katharina; Karch, André; Collins, Steven; Calero, Miguel; Sklaviadis, Theodor; Laplanche, Jean-Louis; Golanska, Ewa; Baldeiras, Ines; Satoh, Katsuya; Sanchez-Valle, Raquel; Ladogana, Anna; Skinningsrud, Anders; Hammarin, Anna-Lena; Mitrova, Eva; Llorens, Franc; Kim, Yong Sun; Green, Alison; Zerr, Inga

    2016-05-01

    At present, the testing of 14-3-3 protein in cerebrospinal fluid (CSF) is a standard biomarker test in suspected sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis. Increasing 14-3-3 test referrals in CJD reference laboratories in the last years have led to an urgent need to improve established 14-3-3 test methods. The main result of our study was the validation of a commercially available 14-3-3 ELISA next to the commonly used Western blot method as a high-throughput screening test. Hereby, 14-3-3 protein expression was quantitatively analyzed in CSF of 231 sCJD and 2035 control patients. We obtained excellent sensitivity/specificity values of 88 and 96% that are comparable to the established Western blot method. Since standard protocols and preanalytical sample handling have become more important in routine diagnostic, we investigated in a further step the reproducibility and stability of 14-3-3 as a biomarker for human prion diseases. Ring trial data from 2009 to 2013 revealed an increase of Fleiss' kappa from 0.51 to 0.68 indicating an improving reliability of 14-3-3 protein detection. The stability of 14-3-3 protein under short-term and long-term storage conditions at various temperatures and after repeated freezing/thawing cycles was confirmed. Contamination of CSF samples with blood appears likely to be an important factor at a concentration of more than 2500 erythrocytes/μL. Hemolysis of erythrocytes with significant release of 14-3-3 protein started after 2 days at room temperature. We first define clear standards for the sample handling, short- and long-term storage of CSF samples as well as the handling of blood- contaminated samples which may result in artificially elevated CSF levels of 14-3-3.

  11. Prion Protein-Hemin Interaction Upregulates Hemoglobin Synthesis: Implications for Cerebral Hemorrhage and Sporadic Creutzfeldt-Jakob Disease.

    PubMed

    Tripathi, Ajai K; Singh, Neena

    2016-01-01

    Hemin is known to induce endocytosis of prion-protein (PrP(C)) from the neuronal plasma membrane, potentially limiting propagation of the disease causing PrP-scrapie (PrP(Sc)) isoform. Hemin is therefore an attractive disease-modifying option for sporadic Creutzfeldt-Jakob disease (sCJD), a human prion disorder with no effective treatment. The hemin-PrP(C) interaction is also of