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Sample records for resembling human sporadic

  1. Social perception of facial resemblance in humans.

    PubMed

    DeBruine, Lisa M; Jones, Benedict C; Little, Anthony C; Perrett, David I

    2008-02-01

    Two lines of reasoning predict that highly social species will have mechanisms to influence behavior toward individuals depending on their degree of relatedness. First, inclusive fitness theory leads to the prediction that organisms will preferentially help closely related kin over more distantly related individuals. Second, evaluation of the relative costs and potential benefits of inbreeding suggests that the degree of kinship should also be considered when choosing a mate. In order to behaviorally discriminate between individuals with different levels of relatedness, organisms must be able to discriminate cues of kinship. Facial resemblance is one such potential cue in humans. Computer-graphic manipulation of face images has made it possible to experimentally test hypotheses about human kin recognition by facial phenotype matching. We review recent experimental evidence that humans respond to facial resemblance in ways consistent with inclusive fitness theory and considerations of the costs of inbreeding, namely by increasing prosocial behavior and positive attributions toward self-resembling images and selectively tempering attributions of attractiveness to other-sex faces in the context of a sexual relationship. PMID:18157627

  2. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda.

    PubMed

    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. 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

  4. Mouse Transcobalamin Has Features Resembling both Human Transcobalamin and Haptocorrin

    PubMed Central

    Hygum, Katrine; Lildballe, Dorte L.; Greibe, Eva H.; Morkbak, Anne L.; Poulsen, Steen S.; Sorensen, Boe S.; Petersen, Torben E.; Nexo, Ebba

    2011-01-01

    In humans, the cobalamin (Cbl) -binding protein transcobalamin (TC) transports Cbl from the intestine and into all the cells of the body, whereas the glycoprotein haptocorrin (HC), which is present in both blood and exocrine secretions, is able to bind also corrinoids other than Cbl. The aim of this study is to explore the expression of the Cbl-binding protein HC as well as TC in mice. BLAST analysis showed no homologous gene coding for HC in mice. Submaxillary glands and serum displayed one protein capable of binding Cbl. This Cbl-binding protein was purified from 300 submaxillary glands by affinity chromatography. Subsequent sequencing identified the protein as TC. Further characterization in terms of glycosylation status and binding specificity to the Cbl-analogue cobinamide revealed that mouse TC does not bind Concanavalin A sepharose (like human TC), but is capable of binding cobinamide (like human HC). Antibodies raised against mouse TC identified the protein in secretory cells of the submaxillary gland and in the ducts of the mammary gland, i.e. at locations where HC is also found in humans. Analysis of the TC-mRNA level showed a high TC transcript level in these glands and also in the kidney. By precipitation to insolubilised antibodies against mouse TC, we also showed that >97% of the Cbl-binding capacity and >98% of the Cbl were precipitated in serum. This indicates that TC is the only Cbl-binding protein in the mouse circulation. Our data show that TC but not HC is present in the mouse. Mouse TC is observed in tissues where humans express TC and/or HC. Mouse TC has features in common with both human TC and HC. Our results suggest that the Cbl-binding proteins present in the circulation and exocrine glands may vary amongst species. PMID:21655200

  5. “Groundsubstance” Resembling Amyloid Extracted from the Cervical Portion of Human Cervix Uteri

    PubMed Central

    Gröschel-Stewart, U.; Hermann, U.; Schwalm, H.

    1973-01-01

    A groundsubstance glycoprotein has been isolated from normal human cervix uteri that has a remarkable resemblance in its primary structure to a protein found in amyloid disease and to other acidic fibrous proteins found in mammalian tissue. Cervical groundsubstance, acidic fibrous protein from human uterus and the cardiac groundsubstance, which is significantly increased in amyloid disease, are immunologically identical or closely related. ImagesFigs. 1-4 PMID:4633712

  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 renal adenocarcinoma in a corn snake (Pantherophis guttatus) resembling human collecting duct carcinoma.

    PubMed

    Kao, Chi-Fei; Chen, Jiun-Liang; Tsao, Wen-Tien; Lee, An-Hsing; Liu, Chen-Hsuan; Wang, Fun-In

    2016-09-01

    A 5-year-old male captive corn snake (Pantherophis guttatus) with caudal coelomic swelling was admitted for surgical treatment. Laparotomy revealed a 5 × 4 × 2.5 cm, firm, expansile, irregularly shaped mass arising from the middle portion of the right kidney with a mild lobulated pattern and mottled white-to-tan. Microscopically, the mass was composed of numerous bizarre angulated tubules of polygonal neoplastic cells separated by a scirrhous stroma with remarkable heterophilic infiltrates. The neoplastic cells were nonciliated and mucin secreting, with abundant brightly eosinophilic cytoplasm. There were marked cellular and nuclear atypia, frequent cell individualization, and stromal invasion, indicative of malignant behavior, which was confirmed by metastasis to the left kidney 1.5 months postoperatively. Both neoplastic epithelial cells and mesenchymal cells contributing to the scirrhous stroma had variable immunopositivity for pan-cytokeratin. The neoplasm was considered a renal adenocarcinoma resembling human collecting duct carcinoma. PMID:27493139

  8. Multi-system progressive angiomatosis in a dog resembling blue rubber bleb nevus syndrome in humans.

    PubMed

    Ide, K; Uchida, N; Iyori, K; Mochizuki, T; Fukushima, R; Iwasaki, T; Nishifuji, K

    2013-04-01

    A six-year-old, neutered, female golden retriever was presented with generalised, dark purple to black cutaneous nodules and gastrointestinal haemorrhage. Histopathologically, all cutaneous nodules were diagnosed as benign cavernous haemangiomas. Endoscopic analysis revealed similar nodules in the oesophagus, stomach and duodenum. At laparotomy, similar nodules were seen on the visceral peritoneal lining of abdominal organs. Metastatic haemangiosarcoma was ruled out based on histological features and lack of primary tumour in spleen, liver or heart ultrasonographically. Blood loss associated with gastrointestinal haemorrhage was managed with blood transfusion. To the authors' knowledge, this is the first canine case of multi-system progressive angiomatosis resembling blue rubber bleb nevus syndrome in humans. PMID:23496103

  9. Rules and Resemblance: Their Changing Balance in the Category Learning of Humans (Homo sapiens) and Monkeys (Macaca mulatta)

    PubMed Central

    Couchman, Justin J.; Coutinho, Mariana V. C.; Smith, J. David

    2010-01-01

    In an early dissociation between intentional and incidental category learning, Kemler Nelson (1984) gave participants a categorization task that could be performed by responding either to a single-dimensional rule or to overall family resemblance. Humans learning intentionally deliberately adopted rule-based strategies; humans learning incidentally adopted family-resemblance strategies. The present authors replicated Kemler Nelson’s human experiment and found a similar dissociation. They also extended her paradigm so as to evaluate the balance between rules and family-resemblance in determining the category decisions of rhesus monkeys. Monkeys heavily favored the family-resemblance strategy. Formal models showed that even after many sessions and thousands of trials, they spread attention across all stimulus dimensions rather than focus on a single, criterial dimension that could also produce perfect categorization. PMID:20384398

  10. 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.

  11. 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. PMID:21080137

  12. Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members

    PubMed Central

    Herms, Jochen; Anliker, Brigitte; Heber, Sabine; Ring, Sabine; Fuhrmann, Martin; Kretzschmar, Hans; Sisodia, Sangram; Müller, Ulrike

    2004-01-01

    The Alzheimer's disease β-amyloid precursor protein (APP) is a member of a larger gene family that includes the amyloid precursor-like proteins, termed APLP1 and APLP2. We previously documented that APLP2−/−APLP1−/− and APLP2−/−APP−/− mice die postnatally, while APLP1−/−APP−/− mice and single mutants were viable. We now report that mice lacking all three APP/APLP family members survive through embryonic development, and die shortly after birth. In contrast to double-mutant animals with perinatal lethality, 81% of triple mutants showed cranial abnormalities. In 68% of triple mutants, we observed cortical dysplasias characterized by focal ectopic neuroblasts that had migrated through the basal lamina and pial membrane, a phenotype that resembles human type II lissencephaly. Moreover, at E18.5 triple mutants showed a partial loss of cortical Cajal Retzius (CR) cells, suggesting that APP/APLPs play a crucial role in the survival of CR cells and neuronal adhesion. Collectively, our data reveal an essential role for APP family members in normal brain development and early postnatal survival. PMID:15385965

  13. Genetic variability of human adenovirus type 8 causing epidemic and sporadic cases of keratoconjunctivitis.

    PubMed

    Fedaoui, Nadia; Ayed, Narjess Ben; Yahia, Ahlem Ben; Hammami, Walid; Touzi, Henda; Triki, Henda

    2016-06-01

    Human adenovirus type 8 (HAdV-8) is a main aetiological agent of keratoconjunctivitis. It has been reported from both epidemic and sporadic cases. The aim of our study was to investigate the genetic characteristics and chronological pattern of HAdV-8 strains that have been circulating in Tunisia over a 14-year period. Fourteen HAdV-8 isolates from a keratoconjunctivitis outbreak that occurred in 2000 and from sporadic cases between 2001 and 2013 were studied. Nucleotide sequences from the hexon, fiber and penton base genes were determined, including hypervariable regions of the hexon (loops 1 and 2), the fiber (knob) and the penton base (HVR 1 and RGD loops). The sequences were compared to each other and to those of HAdV-8 strains. The Tunisian sequences were unique when compared to the previously published sequences. Also, despite a relatively low degree of genetic variation in the three genomic regions, phylogenetic analysis and alignment of amino acid sequences showed that the sequence from the year 2000 and two other sequences from the year 2013 were similar to each other and differed from the isolates that circulated in the intervening year by two main amino acid changes in the loop 1 hexon gene and the knob-fiber gene. Our results confirm the genetic variability of HAdV-8 and document the chronological changes of circulating genetic variants. PMID:26957298

  14. 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

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

    PubMed

    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

  16. 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

  17. Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans

    PubMed Central

    Bianchi, Serena; Duka, Tetyana; Larsen, Michael D.; Janssen, William G. M.; Collins, Zachary; Bauernfeind, Amy L.; Schapiro, Steven J.; Baze, Wallace B.; McArthur, Mark J.; Hopkins, William D.; Wildman, Derek E.; Lipovich, Leonard; Kuzawa, Christopher W.; Jacobs, Bob; Hof, Patrick R.; Sherwood, Chet C.

    2013-01-01

    Neocortical development in humans is characterized by an extended period of synaptic proliferation that peaks in mid-childhood, with subsequent pruning through early adulthood, as well as relatively delayed maturation of neuronal arborization in the prefrontal cortex compared with sensorimotor areas. In macaque monkeys, cortical synaptogenesis peaks during early infancy and developmental changes in synapse density and dendritic spines occur synchronously across cortical regions. Thus, relatively prolonged synapse and neuronal maturation in humans might contribute to enhancement of social learning during development and transmission of cultural practices, including language. However, because macaques, which share a last common ancestor with humans ∼25 million years ago, have served as the predominant comparative primate model in neurodevelopmental research, the paucity of data from more closely related great apes leaves unresolved when these evolutionary changes in the timing of cortical development became established in the human lineage. To address this question, we used immunohistochemistry, electron microscopy, and Golgi staining to characterize synaptic density and dendritic morphology of pyramidal neurons in primary somatosensory (area 3b), primary motor (area 4), prestriate visual (area 18), and prefrontal (area 10) cortices of developing chimpanzees (Pan troglodytes). We found that synaptogenesis occurs synchronously across cortical areas, with a peak of synapse density during the juvenile period (3–5 y). Moreover, similar to findings in humans, dendrites of prefrontal pyramidal neurons developed later than sensorimotor areas. These results suggest that evolutionary changes to neocortical development promoting greater neuronal plasticity early in postnatal life preceded the divergence of the human and chimpanzee lineages. PMID:23754422

  18. 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

  19. 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. PMID:25635096

  20. Transgenic Expression of the Chemokine Receptor Encoded by Human Herpesvirus 8 Induces an Angioproliferative Disease Resembling Kaposi's Sarcoma

    PubMed Central

    Yang, Tong-Yuan; Chen, Shu-Cheng; Leach, Michael W.; Manfra, Denise; Homey, Bernhard; Wiekowski, Maria; Sullivan, Lee; Jenh, Chung-Her; Narula, Satwant K.; Chensue, Stephen W.; Lira, Sergio A.

    2000-01-01

    Human herpesvirus 8 (HHV8, also known as Kaposi's sarcoma [KS]-associated herpesvirus) has been implicated as an etiologic agent for KS, an angiogenic tumor composed of endothelial, inflammatory, and spindle cells. Here, we report that transgenic mice expressing the HHV8-encoded chemokine receptor (viral G protein–coupled receptor) within hematopoietic cells develop angioproliferative lesions in multiple organs that morphologically resemble KS lesions. These lesions are characterized by a spectrum of changes ranging from erythematous maculae to vascular tumors, by the presence of spindle and inflammatory cells, and by expression of vGPCR, CD34, and vascular endothelial growth factor. We conclude that vGPCR contributes to the development of the angioproliferative lesions observed in these mice and suggest that this chemokine receptor may play a role in the pathogenesis of KS in humans. PMID:10662790

  1. Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi's sarcoma.

    PubMed

    Yang, T Y; Chen, S C; Leach, M W; Manfra, D; Homey, B; Wiekowski, M; Sullivan, L; Jenh, C H; Narula, S K; Chensue, S W; Lira, S A

    2000-02-01

    Human herpesvirus 8 (HHV8, also known as Kaposi's sarcoma [KS]-associated herpesvirus) has been implicated as an etiologic agent for KS, an angiogenic tumor composed of endothelial, inflammatory, and spindle cells. Here, we report that transgenic mice expressing the HHV8-encoded chemokine receptor (viral G protein-coupled receptor) within hematopoietic cells develop angioproliferative lesions in multiple organs that morphologically resemble KS lesions. These lesions are characterized by a spectrum of changes ranging from erythematous maculae to vascular tumors, by the presence of spindle and inflammatory cells, and by expression of vGPCR, CD34, and vascular endothelial growth factor. We conclude that vGPCR contributes to the development of the angioproliferative lesions observed in these mice and suggest that this chemokine receptor may play a role in the pathogenesis of KS in humans. PMID:10662790

  2. Ablation of Steroid Receptor Coactivator-3 resembles the human CACT metabolic myopathy

    PubMed Central

    York, Brian; Reineke, Erin L.; Sagen, Jørn V.; Nikolai, Bryan C.; Zhou, Suoling; Louet, Jean-Francois; Chopra, Atul R.; Chen, Xian; Reed, Graham; Noebels, Jeffrey; Adesina, Adekunle M.; Yu, Hui; Wong, Lee-Jun C.; Tsimelzon, Anna; Hilsenbeck, Susan; Stevens, Robert D.; Wenner, Brett R.; Ilkayeva, Olga; Xu, Jianming; Newgard, Christopher B.; O’Malley, Bert W.

    2012-01-01

    Summary Oxidation of lipid substrates is essential for survival in fasting and other catabolic conditions, sparing glucose for the brain and other glucose-dependent tissues. Here we show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene expression. Genetic deficiency of CACT in humans is accompanied by a constellation of metabolic and toxicity phenotypes including hypoketonemia, hypoglycemia, hyperammonemia, and impaired neurologic, cardiac and skeletal muscle performance, each of which is apparent in mice lacking SRC-3 expression. Consistent with human cases of CACT deficiency, dietary rescue with short chain fatty acids drastically attenuates the clinical hallmarks of the disease in mice devoid of SRC-3. Collectively, our results position SRC-3 as a key regulator of β-oxidation. Moreover, these findings allow us to consider platform coactivators such as the SRCs as potential contributors to syndromes such as CACT deficiency, previously considered as monogenic. PMID:22560224

  3. 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

  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. PMID:21538919

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

    PubMed

    York, Ashley; Kutluay, Sebla B; Errando, Manel; Bieniasz, Paul D

    2016-08-01

    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. 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

  7. 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. PMID:25196886

  8. 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

  9. 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? PMID:17264056

  10. Pneumonic Tularemia in Rabbits Resembles the Human Disease as Illustrated by Radiographic and Hematological Changes after Infection

    PubMed Central

    Reed, Douglas S.; Smith, Le'Kneitah; Dunsmore, Tammy; Trichel, Anita; Ortiz, Luis A.; Cole, Kelly Stefano; Barry, Eileen

    2011-01-01

    Background Pneumonic tularemia is caused by inhalation of the gram negative bacterium, Francisella tularensis. Because of concerns that tularemia could be used as a bioterrorism agent, vaccines and therapeutics are urgently needed. Animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures. Principal Findings Rabbits exposed to aerosols containing Francisella tularensis strain SCHU S4 developed a rapidly progressive fatal pneumonic disease. Clinical signs became evident on the third day after exposure with development of a fever (>40.5°C) and a sharp decline in both food and water intake. Blood samples collected on day 4 found lymphopenia and a decrease in platelet counts coupled with elevations in erythrocyte sedimentation rate, alanine aminotransferase, cholesterol, granulocytes and monocytes. Radiographs demonstrated the development of pneumonia and abnormalities of intestinal gas consistent with ileus. On average, rabbits were moribund 5.1 days after exposure; no rabbits survived exposure at any dose (190–54,000 cfu). Gross evaluation of tissues taken at necropsy showed evidence of pathology in the lungs, spleen, liver, kidney and intestines. Bacterial counts confirmed bacterial dissemination from the lungs to the liver and spleen. Conclusions/Significance The pathophysiology of pneumonic tularemia in rabbits resembles what has been reported for humans. Rabbits therefore are a relevant model of the human disease caused by type A strains of F. tularensis. PMID:21931798

  11. Effect of catheter placement on 3-D velocity profiles in curved tubes resembling the human coronary system.

    PubMed

    Krams, R; Wentzel, J J; Cespedes, I; Vinke, R; Carlier, S; van der Steen, A F; Lancee, C T; Slager, C J

    1999-06-01

    Novel measurement techniques based on intravenous ultrasound (IVUS) technology ('IVUS-Flowmetry') require the location of a catheter inside the coronary bed. The present study quantifies disturbances in the 3-D velocity profile induced by catheter placement inside a tube, applying computational fluid dynamics. Two curved, circular meshes (radius K = 0.025 m and K = 0.035 m) with and without a catheter inside the lumen were applied. The catheter was located at the inner curve, the outer curve and at the top position. Boundary conditions were: no slip on the wall, zero stress at the outlet, uniform inflow with entrance velocities of 0.1, 0.2 and 0.4 m/s. Curvature-associated centrifugal forces shifted the maximal velocity to the outer curve and introduced two symmetrical vortices. Additional catheter placement redistributed the 3-D axial velocity field away from the catheter, which was accompanied by the appearance of multiple low-strength vortices. In addition, peak axial velocity increased, peak secondary velocities decreased, axial pressure drop increased and shear stress increased. Flow calculations simulated to resemble IVUS-based flowmetry changed by only 1% after considering secondary velocity. In conclusion, placement of a catheter inside a curved tube resembling the human coronary system changes the velocity field and reduces secondary patterns. The present study supports the usefulness of catheter-based flowmetry during resting flow conditions. During hyperemic flow conditions, flow measurements might be accompanied by large axial pressure drops because the catheter, itself, might act as a significant stenosis. PMID:10414897

  12. 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

  13. Human mutL homolog 1 expression characteristic and prognostic effect on patients with sporadic colorectal cancer

    PubMed Central

    Pu, Chibin; Ren, Weiguo; Sun, Zhenqiang; Yu, Xianbo; Yuan, Wei; Huang, Mingyu; Shen, Shourong; Wang, Xiaoyan

    2015-01-01

    The aim of the present study was to analyze the relationship between aberrant human mutL homolog 1 (hMLH1) expression and clinicopathological parameters of patients with sporadic colorectal cancer, and to explore the prognostic effect of aberrant hMLH1 expression in these patients. The relationship was measured by chi-square test and Fisher’s exact test. Survival analysis was performed with Kaplan-Meier analysis and Cox regression model to measure 5-year disease-free survival (DFS) and 5-year overall survival (OS) rates. Totally 17.13% of the patients with sporadic colorectal cancer showed aberrant nuclear staining for hMLH1 expression. Aberrant hMLH1 expression was related with tumor pathologic types, tumor location and TNM staging (P<0.05) in the patients with sporadic colorectal cancer. Cox regression analysis indicated important prognostic factors were age (RR: 1.021, 95% CI: 1.003-1.039, P=0.023), mucinous adenocarcinoma (RR: 2.603, 95% CI: 1.705-3.974, P<0.0001), TNM staging (RR: 2.071, 95% CI: 1.170-3.666, P=0.012), lymphangion invasion (RR: 2.013, 95% CI: 1.227-3.303, P=0.006) and aberrant hMLH1 expression (RR: 0.414, 95% CI: 0.216-0.791, P=0.008). Consequently, hMLH1 expression level is related with some clinicopathologic features. Aberrant hMLH1 expression plays a significant part in prognosis for patients with sporadic colorectal cancer and it will promisingly become an independent prognostic factor. PMID:26770629

  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. Absence of somatic alterations of the EB1 gene adenomatous polyposis coli-associated protein in human sporadic colorectal cancers.

    PubMed Central

    Jaïs, P.; Sabourin, J. C.; Bombled, J.; Rougier, P.; Lasser, P.; Duvillard, P.; Bénard, J.; Bressac-de Paillerets, B.

    1998-01-01

    The human EB1 gene product was recently found, by a yeast two-hybrid screening, to be associated with the carboxy terminus of the APC (adenomatous polyposis coli) protein, the product of a tumour-suppressor gene thought to act as a gatekeeper in colorectal carcinogenesis. Because virtually all of the APC mutations result in the synthesis of carboxy-terminal truncated proteins, mutant APC proteins are expected to lose their ability to interact with EB1 gene product. Thus, the interaction between APC and EB1 proteins may be important for the tumour-suppressor activity of APC protein, and raises the hypothesis that EB1 is also involved in sporadic colorectal tumorigenesis. To investigate this hypothesis, somatic mutations in the entire coding sequence of EB1 cDNA were searched by reverse transcriptase single-strand conformational polymorphism (SSCP) analysis in 21 sporadic colorectal cancers and seven adenomas. None of these tumours contained somatic mutation, whereas a silent cDNA variant was identified in 14% of alleles. Furthermore, to investigate whether EB1 locus was included within a region subjected to losses of heterozygosity, four polymorphism markers surrounding EB1 locus were surveyed. Only one out of 28 colorectal tumours contained a loss of heterozygosity at the D20S107 marker. In conclusion, the present findings strongly suggest that EB1 gene is not involved in somatic colorectal carcinogenesis. Images Figure 2 Figure 3 PMID:9823979

  16. Population Structure of Listeria monocytogenes Serotype 4b Isolates from Sporadic Human Listeriosis Cases in the United States from 2003 to 2008

    PubMed Central

    Ward, Todd J.; Graves, Lewis M.; Tarr, Cheryl L.; Siletzky, Robin M.; Kathariou, Sophia

    2014-01-01

    Listeria monocytogenes can cause severe food-borne disease (listeriosis). Numerous outbreaks have involved three serotype 4b epidemic clones (ECs): ECI, ECII, and ECIa. However, little is known about the population structure of L. monocytogenes serotype 4b from sporadic listeriosis in the United States, even though most cases of human listeriosis are in fact sporadic. Here we analyzed 136 serotype 4b isolates from sporadic cases in the United States, 2003 to 2008, utilizing multiple tools including multilocus genotyping, pulsed-field gel electrophoresis, and sequence analysis of the inlAB locus. ECI, ECII, and ECIa were frequently encountered (32, 17, and 7%, respectively). However, annually 30 to 68% of isolates were outside these ECs, and several novel clonal groups were identified. An estimated 33 and 17% of the isolates, mostly among the ECs, were resistant to cadmium and arsenic, respectively, but resistance to benzalkonium chloride was uncommon (3%) among the sporadic isolates. The frequency of clonal groups fluctuated within the 6-year study period, without consistent trends. However, on several occasions, temporal clusters of isolates with indistinguishable genotypes were detected, suggesting the possibility of hidden multistate outbreaks. Our analysis suggests a complex population structure of serotype 4b L. monocytogenes from sporadic disease, with important contributions by ECs and several novel clonal groups. Continuous monitoring will be needed to assess long-term trends in clonality patterns and population structure of L. monocytogenes from sporadic listeriosis. PMID:24705322

  17. 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

  18. The zebrafish mutant lbk/vam6 resembles human multisystemic disorders caused by aberrant trafficking of endosomal vesicles.

    PubMed

    Schonthaler, Helia B; Fleisch, Valerie C; Biehlmaier, Oliver; Makhankov, Yuri; Rinner, Oliver; Bahadori, Ronja; Geisler, Robert; Schwarz, Heinz; Neuhauss, Stephan C F; Dahm, Ralf

    2008-01-01

    The trafficking of intracellular vesicles is essential for a number of cellular processes and defects in this process have been implicated in a wide range of human diseases. We identify the zebrafish mutant lbk as a novel model for such disorders. lbk displays hypopigmentation of skin melanocytes and the retinal pigment epithelium (RPE), an absence of iridophore reflections, defects in internal organs (liver, intestine) as well as functional defects in vision and the innate immune system (macrophages). Positional cloning, an allele screen, rescue experiments and morpholino knock-down reveal a mutation in the zebrafish orthologue of the vam6/vps39 gene. Vam6p is part of the HOPS complex, which is essential for vesicle tethering and fusion. Affected cells in the lbk RPE, liver, intestine and macrophages display increased numbers and enlarged intracellular vesicles. Physiological and behavioural analyses reveal severe defects in visual ability in lbk mutants. The present study provides the first phenotypic description of a lack of vam6 gene function in a multicellular organism. lbk shares many of the characteristics of human diseases and suggests a novel disease gene for pathologies associated with defective vesicle transport, including the arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, the Hermansky-Pudlak syndrome, the Chediak-Higashi syndrome and the Griscelli syndrome. PMID:18077594

  19. 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

  20. 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...

  1. 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...

  2. 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

  3. 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

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

    PubMed Central

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

    2013-01-01

    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. PMID:23355383

  5. Introduction to Sporadic Groups

    NASA Astrophysics Data System (ADS)

    Boya, Luis J.

    2011-01-01

    This is an introduction to finite simple groups, in particular sporadic groups, intended for physicists. After a short review of group theory, we enumerate the 1+1+16=18 families of finite simple groups, as an introduction to the sporadic groups. These are described next, in three levels of increasing complexity, plus the six isolated ''pariah'' groups. The (old) five Mathieu groups make up the first, smallest order level. The seven groups related to the Leech lattice, including the three Conway groups, constitute the second level. The third and highest level contains the Monster group M, plus seven other related groups. Next a brief mention is made of the remaining six pariah groups, thus completing the 5+7+8+6=26 sporadic groups. The review ends up with a brief discussion of a few of physical applications of finite groups in physics, including a couple of recent examples which use sporadic groups.

  6. 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

  7. Association of allelic losses on human chromosomal arms 11Q and 16Q in sporadic breast cancer.

    PubMed

    Schmutzler, R K; Fimmers, R; Bierhoff, E; Lohmar, B; Homann, A; Speiser, P; Kubista, E; Jaeger, K; Krebs, D; Zeillinger, R; Wiestler, O D; Von Deimling, A

    1996-08-22

    Breast-carcinoma development presumably results from multiple mutational events in tumor-associated genes. Certain results indicate that some tumor-suppressor genes may combine their pathogenetic potential to synergistically promote tumor growth. In an effort to identify such mechanisms in breast tumors, a series of 77 (group I) paired blood tumor samples from patients with sporadic mammary carcinomas was analyzed for loss of heterozygosity with 15 polymorphic markers on the chromosomal arms 7q, 11q, 13q, 16q, 17p and 17q. A significant association was observed for the combination of allelic losses on chromosomes 11q and 16q. In order to confirm these findings, we studied a second independent series of 189 breast-tumor patients (group 2) with comparable histopathological tumor stages. Group 2 was examined for the same genetic alterations using the identical set of polymorphic markers. The data from this group confirmed the detected association of loss of heterozygosity on chromosomes 11q and 16q and indicate the cooperation of putative tumor-suppressor genes on the chromosomal arms 11q and 16q in a sub-set of breast carcinomas. The regions involved harbor the candidate genes ATM (mutated in ataxiatelangiectasia) on chromosome 11q23 and UVO (uvomorulin, cadherin E) and BBCI (breast basic conserved I) on chromosome 16q22-q24. PMID:8797873

  8. Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer.

    PubMed

    Cui, Guanglin; Qi, Haili; Gundersen, Mona D; Yang, Hang; Christiansen, Ingrid; Sørbye, Sveinung W; Goll, Rasmus; Florholmen, Jon

    2015-02-01

    Most sporadic colorectal cancers (CRCs) develop from preformed adenomas. Cytokines are involved in the transition from adenoma to CRC. Interleukin-33 (IL-33) is a newly discovered proinflammatory cytokine belonging to the IL-1 cytokine family and involved in the development of chronic inflammation and cancer. The aim of this study was to evaluate the dynamics of the IL-33/ST2 axis during the sequence of progression from normal colorectum to adenoma to carcinoma and to investigate the association of IL-33 and ST2 expression with clinicopathological parameters and prognosis. The results demonstrated that the levels of IL-33 and ST2 in adenomas (n = 50), determined by real-time PCR, were significantly higher than those of normal controls (n = 30); the levels of both IL-33/ST mRNA in CRCs (n = 50) were higher than in normal controls but lower than in adenomas. Further analysis revealed that the expression level of ST2 in CRCs was associated with tumor/node/metastasis (TNM) stage. The log-rank test showed that neither the IL-33 nor the ST2 expression level was correlated with overall survival in patients with CRC. The increased expression of IL-33/ST2 in adenomas and CRC tissues was confirmed by immunohistochemistry and was observed in both the tumor stromal cells and adenomatous/cancerous cells. Notably, increased densities of IL-33-positive and ST2-positive microvessels were found in the stroma of adenomas and CRCs. In conclusion, increased expression of the IL-33/ST2 axis along the colorectal adenoma-carcinoma sequence might be involved in the neoplastic transformation via the participation of this axis in the regulation of angiogenesis. PMID:25324197

  9. Resemblance and investment in children.

    PubMed

    Dolinska, Barbara

    2013-01-01

    According to evolutionary explanations men hardly ever are absolutely certain about their biological fatherhood therefore they must seek various sources of information to subjectively establish whether they are the genetic fathers of the children they raise. Apicella and Marlowe (2004) showed that fathers who perceived greater similarity between their children and themselves were willing to invest more resources (e.g., time, money, care) in their offspring presumably because the perceived resemblance indicated to the fathers their genetic relatedness with their children. The present study extended the design of Apicella and Marlowe's original study and included both fathers and mothers as participants. Parents were recruited by a female confederate at the airport and at the railway station in Wroclaw (Poland). Multiple regression analyses showed that perceived resemblance predicted parental investment in the child for both men and women. The fact that mothers' declarations of investment in their children also depended on the perceived resemblance factor is not consistent with evolutionary formulations delineated by Apicella and Marlowe (2004; 2007). Future studies must resolve the issue of whether the resemblance-investment relation in fathers results from men relaying on child's resemblance to themselves as an indicator of their own biological paternity, or whether it results from the more parsimonious phenomenon that people in general are attracted more to other people who are similar to them. PMID:22385106

  10. Characterisation of human outbreaks of brucellosis and sporadic cases by the use of hyper-variable octameric oligonucleotide fingerprint (HOOF) variable number tandem repeats.

    PubMed

    Valdezate, S; Cervera, I; Hernandez, P; Navarro, A; Saéz Nieto, J A

    2007-09-01

    Hyper-variable octameric oligonucleotide fingerprints (HOOFs) enable typing of Brucella spp. by targeting the 8-bp tandem repeat in eight loci that vary in number (variable number tandem repeats; VNTRs). Brucella is one of the most important zoonotic pathogens, because of its public health and economic consequences. To assess the role of HOOFs as epidemiological markers for Brucella melitensis, which is the main species involved in human brucellosis in Spain, 87 sporadic and outbreak isolates were investigated; these originated from broad or more restricted geographical locations, including unrelated (n = 42), semi-related (n = 19) and closely related (n = 26) groups of isolates. Distinct HOOFs were detected in the entire (n = 74), unrelated (n = 42), semi-related (n = 19) and closely related (n = 13) groups. Seven of the eight VNTR markers investigated identified multiple alleles in the four groups of isolates. Using the composite data for eight VNTRs, a diversity value of 0.98 was calculated for the entire population, taking into account single- and double-locus variants. A high correlation (R = 0.98) between the maximum copy number and the number of alleles was observed. The most polymorphic markers were VNTR-1, VNTR-4, VNTR-5 and VNTR-7 (D > OR = 0.8). Characterisation of B. melitensis isolates by HOOFs enabled the recognition of related human cases and the exchange of molecular epidemiological information concerning a spreading clone, thus improving brucellosis surveillance. PMID:17686139

  11. 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…

  12. Sporadic postinfectious neuromyasthenia

    PubMed Central

    Salit, Irving E.

    1985-01-01

    Outbreaks of epidemic neuromyasthenia have occurred throughout the world for many years, but sporadic cases have only recently been recognized. Fifty consecutive previously well patients with prolonged and excessive fatigue after an apparent acute infection were investigated. Most were well educated, active, unmarried women aged 30 to 40 years. The precipitating infection had many clinical presentations. The chronic phase of the illness was characterized by a fairly common set of symptoms. Physical examination and laboratory testing generally gave normal results. Of the 50 patients 16 were found to be infected with Epstein-Barr virus, 7 with other viruses, 4 with parasites and 2 with Mycoplasma pneumoniae. The caustive agent was not known in 22 cases. The mean duration of the illness was 27.6 months, and the mean proportion of time lost from work or school was 39%. Drug therapy was not beneficial; supportive therapy was useful. Further investigation is required to determine optimal management of sporadic neuromyasthenia. PMID:4042036

  13. The epidemiology of sporadic human infections with unusual cryptosporidia detected during routine typing in England and Wales, 2000-2008.

    PubMed

    Elwin, K; Hadfield, S J; Robinson, G; Chalmers, R M

    2012-04-01

    Routine typing of 14 469 isolates from human cryptosporidiosis cases between 2000 and 2008 revealed that 7439 (51·4%) were Cryptosporidium (C.) hominis, 6372 (44·0%) C. parvum, 51 (0·4%) both C. hominis and C. parvum, 443 (3·1%) were not typable and 164 (1·1%) were other Cryptosporidium species or genotypes. Of the latter, 109 were C. meleagridis, 38 C. felis, 11 C. ubiquitum, one C. canis, two horse, two novel and one skunk genotype. C. hominis monkey genotype and C. cuniculus were identified in a separate study. Patients with unusual infections were older than those with C. hominis (P<0·01) or C. parvum (P<0·01) and were more likely to be immunocompromised (Fisher's exact P<0·01). Forty-one percent of unusual cases had travelled abroad, mainly to the Indian subcontinent. Significant risk factors in those with unusual species were travel abroad (C. meleagridis, P<0·01), being immunocompromised (C. felis, Fisher's exact P=0·02), and contact with cats (C. felis, Fisher's exact P=0·02). PMID:21733255

  14. Nighttime sporadic-E.

    NASA Technical Reports Server (NTRS)

    Beer, T.; Moorcroft, D. R.

    1972-01-01

    At night, internal atmospheric gravity waves are able to induce drift instabilities in the ionospheric plasma. Nighttime constant height type sporadic-E(Esc) may then be explained as an effect due to the combined effect of ionization movement due to the wind shear mechanism and due to the cross-field gradient drifts. This combined concept provides a qualitative explanation of the rocket observed nighttime electron density profiles, of the speeds of the Esc irregularities and of the variations of Esc with latitude and electric field strength.-

  15. Searching for a good model for systemic sclerosis: the molecular profile and vascular changes occurring in UCD-200 chickens strongly resemble the early phase of human systemic sclerosis

    PubMed Central

    Di Benedetto, Paola; Dietrich, Hermann; Ruscitti, Piero; Liakouli, Vasiliki; Carubbi, Francesco; Pantano, Ilenia; Berardicurti, Onorina; Sgonc, Roswitha; Giacomelli, Roberto

    2016-01-01

    Introduction Vascular injury and endothelial cell (EC) apoptosis are the earliest events in systemic sclerosis (SSc), before the onset of fibrosis, and stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGFA), endothelin-1 (ET-1) and platelet-derived growth factors (PDGF-BB) represent the key molecules to study the link between vascular injury and fibrosis during SSc. The University of California at Davis line 200 (UCD-200) chickens display the same hallmarks of human SSc: vascular occlusion, perivascular lymphocytic infiltration and fibrosis of skin and internal organs. In this study we assessed both cytokines and growth factors involved in the early phases of the UCD-200 chickens’ skin lesions, to determine whether these animals might represent an appropriate experimental model to study the pathogenesis of SSc. Material and methods Immunofluorescence analysis was performed on human SSc skin, human healthy control (hHC) skin, UCD-200 combs and HC H.B15 chicken (cHC) combs, using anti-SDF-1, CXCR4, VEGFA, VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), ET-1, ET receptor A (ETAR), ET receptor B (ETBR), PDGF-BB, and PDGF receptor (PDGFR) antibodies. The plasma concentrations of SDF-1, VEGFA, ET-1 and PDGF-BB were determined by ELISA. Results All the molecules analyzed showed higher levels in SSc patients and UCD-200 chickens than in hHC and cHC. Furthermore, the levels of the assessed molecules paralleled the severity of comb involvement. Conclusions The molecular similarities between avian and human SSc, observed in this study, suggest that the UCD-200 chickens are an interesting model for translational approaches to SSc. PMID:27478465

  16. A RAB3GAP1 SINE Insertion in Alaskan Huskies with Polyneuropathy, Ocular Abnormalities, and Neuronal Vacuolation (POANV) Resembling Human Warburg Micro Syndrome 1 (WARBM1)

    PubMed Central

    Wiedmer, Michaela; Oevermann, Anna; Borer-Germann, Stephanie E.; Gorgas, Daniela; Shelton, G. Diane; Drögemüller, Michaela; Jagannathan, Vidhya; Henke, Diana; Leeb, Tosso

    2015-01-01

    We observed a hereditary phenotype in Alaskan Huskies that was characterized by polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV). The affected dogs developed a progressive severe ataxia, which led to euthanasia between 8 and 16 months of age. The pedigrees were consistent with a monogenic autosomal recessive inheritance. We localized the causative genetic defect to a 4 Mb interval on chromosome 19 by a combined linkage and homozygosity mapping approach. Whole genome sequencing of one affected dog, an obligate carrier, and an unrelated control revealed a 218-bp SINE insertion into exon 7 of the RAB3GAP1 gene. The SINE insertion was perfectly associated with the disease phenotype in a cohort of 43 Alaskan Huskies, and it was absent from 541 control dogs of diverse other breeds. The SINE insertion induced aberrant splicing and led to a transcript with a greatly altered exon 7. RAB3GAP1 loss-of-function variants in humans cause Warburg Micro Syndrome 1 (WARBM1), which is characterized by additional developmental defects compared to canine POANV, whereas Rab3gap1-deficient mice have a much milder phenotype than either humans or dogs. Thus, the RAB3GAP1 mutant Alaskan Huskies provide an interesting intermediate phenotype that may help to better understand the function of RAB3GAP1 in development. Furthermore, the identification of the presumed causative genetic variant will enable genetic testing to avoid the nonintentional breeding of affected dogs. PMID:26596647

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

    PubMed

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

    2015-08-01

    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

  18. 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

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

    PubMed

    Abdul Aziz, Siti Hajar; John, Cini Mathew; Mohamed Yusof, Nur Intan Saidaah; Nordin, Massita; Ramasamy, Rajesh; Adam, Aishah; Mohd Fauzi, Fazlin

    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

  20. Archaic artifacts resembling celestial spheres

    NASA Astrophysics Data System (ADS)

    Dimitrakoudis, S.; Papaspyrou, P.; Petoussis, V.; Moussas, X.

    We present several bronze artifacts from the Archaic Age in Greece (750-480 BC) that resemble celestial spheres or forms of other astronomical significance. They are studied in the context of the Dark Age transition from Mycenaean Age astronomical themes to the philosophical and practical revival of astronomy in the Classical Age with its plethora of astronomical devices. These artifacts, mostly votive in nature are spherical in shape and appear in a variety of forms their most striking characteristic being the depiction of meridians and/or an equator. Most of those artifacts come from Thessaly, and more specifically from the temple of Itonia Athena at Philia, a religious center of pan-Hellenic significance. Celestial spheres, similar in form to the small artifacts presented in this study, could be used to measure latitudes, or estimate the time at a known place, and were thus very useful in navigation.

  1. Familial resemblance for serum metabolite concentrations.

    PubMed

    Draisma, Harmen H M; Beekman, Marian; Pool, René; van Ommen, Gert-Jan B; Adamski, Jerzy; Prehn, Cornelia; Vaarhorst, Anika A M; de Craen, Anton J M; Willemsen, Gonneke; Slagboom, P Eline; Boomsma, Dorret I

    2013-10-01

    Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of familial resemblance for the concentrations in human serum of more than 100 metabolites, measured using a targeted metabolomics platform. Age- and sex-corrected monozygotic twin correlations, midparent-offspring regression coefficients, and spouse correlations in subjects from two independent cohorts (Netherlands Twin Register and Leiden Longevity Study) were estimated for each metabolite. In the Netherlands Twin Register subjects, who were largely fasting, we found significant monozygotic twin correlations for 121 out of 123 metabolites. Heritability was confirmed by midparent-offspring regression. For most detected metabolites, the correlations between spouses were considerably lower than those between twins, indicating a contribution of genetic effects to familial resemblance. Remarkably high heritability was observed for free carnitine (monozygotic twin correlation 0.66), for the amino acids serine (monozygotic twin correlation 0.77) and threonine (monozygotic twin correlation 0.64), and for phosphatidylcholine acyl-alkyl C40:3 (monozygotic twin correlation 0.77). For octenoylcarnitine, a consistent point estimate of approximately 0.50 was found for the spouse correlations in the two cohorts as well as for the monozygotic twin correlation, suggesting that familiality for this metabolite is explained by shared environment. We conclude that for the majority of metabolites targeted by the used metabolomics platform, the familial resemblance of serum concentrations is largely genetic. Our results contribute to the knowledge of the heritability of fasting serum metabolite concentrations, which is relevant for biomarker research. PMID:23985338

  2. Genetics Home Reference: sporadic hemiplegic migraine

    MedlinePlus

    ... Diagnosis & Management These resources address the diagnosis or management of sporadic hemiplegic migraine: Genetic Testing Registry: Migraine, sporadic hemiplegic Journal of the American Medical Association Patient Page: Migraine ...

  3. 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

    Peres-Dias, Quezia Nunes; Oliveira, Claudete Diniz; Souza, Marcos Barbosa de; Meira, Antônio de Medeiros; Villanova, Ciro Benigno

    2016-07-11

    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

  4. 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

  5. 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.

  6. Midlatitude sporadic-E layers

    NASA Technical Reports Server (NTRS)

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

    1981-01-01

    Rocket borne probes and incoherent scatter radar were demonstrated to be effective methods of studying the structure of midlatitude sporadic E layers. Layers are formed when metal ions are converged vertically in a wind shear to produce a local enhancement of electron density. Rocket and radar observations show that the layers may occassionally have complex structure produced by an unstable wind shear. The partial transparency to radio waves of sporadic E layers is shown to be due to localized regions of high electron density.

  7. Does sporadic Leber's disease exist?

    PubMed

    Nikoskelainen, E; Nummelin, K; Savontaus, M L

    1988-12-01

    This study gives some illustrative case reports of the difficulties in the diagnosis of Leber's hereditary optic neuroretinopathy. It underlies the importance of careful family history and search for peripapillary microangiopathy in the maternal relatives of patients suspected to suffer from Leber's disease. The article casts doubt on the existence of so-called sporadic Leber's disease. PMID:2977137

  8. 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.

  9. Darwinian behavior in a cold, sporadically fed pool of ribonucleotides.

    PubMed

    Yarus, Michael

    2012-09-01

    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 >10(4) 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. PMID:22946838

  10. 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

  11. Somatic PIK3CA mutations as a driver of sporadic venous malformations.

    PubMed

    Castel, Pau; Carmona, F Javier; Grego-Bessa, Joaquim; Berger, Michael F; Viale, Agnès; Anderson, Kathryn V; Bague, Silvia; Scaltriti, Maurizio; Antonescu, Cristina R; Baselga, Eulàlia; Baselga, José

    2016-03-30

    Venous malformations (VM) are vascular malformations characterized by enlarged and distorted blood vessel channels. VM grow over time and cause substantial morbidity because of disfigurement, bleeding, and pain, representing a clinical challenge in the absence of effective treatments (Nguyenet al, 2014; Uebelhoeret al, 2012). Somatic mutations may act as drivers of these lesions, as suggested by the identification ofTEKmutations in a proportion of VM (Limayeet al, 2009). We report that activatingPIK3CAmutations gives rise to sporadic VM in mice, which closely resemble the histology of the human disease. Furthermore, we identified mutations inPIK3CAand related genes of the PI3K (phosphatidylinositol 3-kinase)/AKT pathway in about 30% of human VM that lackTEKalterations.PIK3CAmutations promote downstream signaling and proliferation in endothelial cells and impair normal vasculogenesis in embryonic development. We successfully treated VM in mouse models using pharmacological inhibitors of PI3Kα administered either systemically or topically. This study elucidates the etiology of a proportion of VM and proposes a therapeutic approach for this disease. PMID:27030594

  12. Somatic PIK3CA mutations as a driver of sporadic venous malformations

    PubMed Central

    Castel, Pau; Carmona, F. Javier; Grego-Bessa, Joaquim; Berger, Michael F.; Viale, Agnès; Anderson, Kathryn V.; Bague, Silvia; Scaltriti, Maurizio; Antonescu, Cristina R.; Baselga, Eulàlia; Baselga, José

    2016-01-01

    Venous malformations (VM) are vascular malformations characterized by enlarged and distorted blood vessel channels. VM grow over time and cause substantial morbidity because of disfigurement, bleeding, and pain, representing a clinical challenge in the absence of effective treatments (Nguyen et al., 2014; Uebelhoer et al., 2012). Somatic mutations may act as drivers of these lesions, as suggested by the identification of TEK mutations in a proportion of VM (Limaye et al., 2009). We report that activating PIK3CA mutations gives rise to sporadic VM in mice, which closely resemble the histology of the human disease. Furthermore, we identified mutations in PIK3CA and related genes of the PI3K (phosphatidylinositol 3-kinase)/AKT pathway in about 30% of human VM that lack TEK alterations. PIK3CA mutations promote downstream signaling and proliferation in endothelial cells and impair normal vasculogenesis in embryonic development. We successfully treated VM in mouse models using pharmacological inhibitors of PI3Kα administered either systemically or topically. This study elucidates the etiology of a proportion of VM and proposes a therapeutic approach for this disease. PMID:27030594

  13. Implicit trustworthiness ratings of self-resembling faces activate brain centers involved in reward.

    PubMed

    Platek, Steven M; Krill, Austen L; Wilson, Benjamin

    2009-01-01

    On the basis of Hamilton's (Hamilton, W. D. (1964). The genetical evolution of social behavior I, II. Journal of Theoretical Biology, 7, 17-52) theory of inclusive fitness, self-facial resemblance is hypothesized as a mechanism for self-referent phenotypic matching by which humans can detect kin. To understand the mechanisms underlying pro-sociality toward self-resembling faces, we investigated the neural correlates of implicit trustworthiness ratings for self-resembling faces. Here we show that idiosyncratic trustworthiness ratings of self-resembling faces predict brain activation in the ventral inferior, middle and medial frontal gyri, substrates involved in reward processing. These findings demonstrate that neural reward centers are implicated in evaluating implicit pro-social behaviors toward self-resembling faces. These findings suggest that humans have evolved to use neurocomputational architecture dedicated to face processing and reward evaluation for the differentiation of kin, which drives implicit idiosyncratic affectively regulated social interactions. PMID:18761362

  14. Aloe vera non-decolorized whole leaf extract-induced large intestinal tumors in F344 rats share similar molecular pathways with human sporadic colorectal tumors.

    PubMed

    Pandiri, Arun R; Sills, Robert C; Hoenerhoff, Mark J; Peddada, Shyamal D; Ton, Thai-Vu T; Hong, Hue-Hua L; Flake, Gordon P; Malarkey, David E; Olson, Greg R; Pogribny, Igor P; Walker, Nigel J; Boudreau, Mary D

    2011-12-01

    Aloe vera is one of the most commonly used botanicals for various prophylactic and therapeutic purposes. Recently, NTP/NCTR has demonstrated a dose-dependent increase in large intestinal tumors in F344 rats chronically exposed to Aloe barbadensis Miller (Aloe vera) non-decolorized whole leaf extract (AVNWLE) in drinking water. The morphological and molecular pathways of AVNWLE-induced large intestinal tumors in the F344 rats were compared to human colorectal cancer (hCRC) literature. Defined histological criteria were used to compare AVNWLE-induced large intestinal tumors with hCRC. The commonly mutated genes (Kras, Ctnnb1, and Tp53) and altered signaling pathways (MAPK, WNT, and TGF-β) important in hCRC were evaluated within AVNWLE-induced large intestinal tumors. Histological evaluation of the large intestinal tumors indicated eight of twelve adenomas (Ads) and four of twelve carcinomas (Cas). Mutation analysis of eight Ads and four Cas identified point mutations in exons 1 and 2 of the Kras gene (two of eight Ads, two of four Cas), and in exon 2 of the Ctnnb1 gene (three of eight Ads, one of four Cas). No Tp53 (exons 5-8) mutations were found in Ads or Cas. Molecular pathways important in hCRC such as MAPK, WNT, and TGF-β signaling were also altered in AVNWLE-induced Ads and Cas. In conclusion, the AVNWLE-induced large intestinal tumors in F344 rats share several similarities with hCRC at the morphological and molecular levels. PMID:21937742

  15. Aloe vera Non-Decolorized Whole Leaf Extract-Induced Large Intestinal Tumors in F344 Rats Share Similar Molecular Pathways with Human Sporadic Colorectal Tumors

    PubMed Central

    Pandiri, Arun R.; Sills, Robert C.; Hoenerhoff, Mark J.; Peddada, Shyamal D.; Ton, Thai-Vu T.; Hong, Hue-Hua L.; Flake, Gordon P.; Malarkey, David E.; Olson, Greg R.; Pogribny, Igor P.; Walker, Nigel J.; Boudreau, Mary D.

    2016-01-01

    Aloe vera is one of the most commonly used botanicals for various prophylactic and therapeutic purposes. Recently, NTP/NCTR has demonstrated a dose-dependent increase in large intestinal tumors in F344 rats chronically exposed to Aloe barbadensis Miller (Aloe vera) non-decolorized whole leaf extract (AVNWLE) in drinking water. The morphological and molecular pathways of AVNWLE-induced large intestinal tumors in the F344 rats were compared to human colorectal cancer (hCRC) literature. Defined histological criteria were used to compare AVNWLE-induced large intestinal tumors with hCRC. The commonly mutated genes (Kras, Ctnnb1, and Tp53) and altered signaling pathways (MAPK, WNT, and TGF-β) important in hCRC were evaluated within AVNWLE-induced large intestinal tumors. Histological evaluation of the large intestinal tumors indicated eight of twelve adenomas (Ads) and four of twelve carcinomas (Cas). Mutation analysis of eight Ads and four Cas identified point mutations in exons 1 and 2 of the Kras gene (two of eight Ads, two of four Cas), and in exon 2 of the Ctnnb1 gene (three of eight Ads, one of four Cas). No Tp53 (exons 5–8) mutations were found in Ads or Cas. Molecular pathways important in hCRC such as MAPK, WNT, and TGF-β signaling were also altered in AVNWLE-induced Ads and Cas. In conclusion, the AVNWLE-induced large intestinal tumors in F344 rats share several similarities with hCRC at the morphological and molecular levels. PMID:21937742

  16. High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

    PubMed Central

    2009-01-01

    Background The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. Methods We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. Results HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001). Conclusion Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican

  17. Quantitative Expression Analysis of APP Pathway and Tau Phosphorylation-Related Genes in the ICV STZ-Induced Non-Human Primate Model of Sporadic Alzheimer’s Disease

    PubMed Central

    Park, Sang-Je; Kim, Young-Hyun; Nam, Gyu-Hwi; Choe, Se-Hee; Lee, Sang-Rae; Kim, Sun-Uk; Kim, Ji-Su; Sim, Bo-Woong; Song, Bong-Seok; Jeong, Kang-Jin; Lee, Youngjeon; Park, Young Il; Lee, Kyoung-Min; Huh, Jae-Won; Chang, Kyu-Tae

    2015-01-01

    The accumulation and aggregation of misfolded proteins in the brain, such as amyloid-β (Aβ) and hyperphosphorylated tau, is a neuropathological hallmark of Alzheimer’s disease (AD). Previously, we developed and validated a novel non-human primate model for sporadic AD (sAD) research using intracerebroventricular administration of streptozotocin (icv STZ). To date, no characterization of AD-related genes in different brain regions has been performed. Therefore, in the current study, the expression of seven amyloid precursor protein (APP) pathway-related and five tau phosphorylation-related genes was investigated by quantitative real-time PCR experiments, using two matched-pair brain samples from control and icv STZ-treated cynomolgus monkeys. The genes showed similar expression patterns within the control and icv STZ-treated groups; however, marked differences in gene expression patterns were observed between the control and icv STZ-treated groups. Remarkably, other than β-secretase (BACE1) and cyclin-dependent kinase 5 (CDK5), all the genes tested showed similar expression patterns in AD models compared to controls, with increased levels in the precuneus and occipital cortex. However, significant changes in gene expression patterns were not detected in the frontal cortex, hippocampus, or posterior cingulate. Based on these results, we conclude that APP may be cleaved via the general metabolic mechanisms of increased α- and γ-secretase levels, and that hyperphosphorylation of tau could be mediated by elevated levels of tau protein kinase, specifically in the precuneus and occipital cortex. PMID:25622254

  18. 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

  19. Sporadic Ataxia and Multiple System Atrophy (MSA)

    MedlinePlus

    ... sporadic ataxia and MSA. The disorders include rapid eye movement (REM) sleep behavior disorder, a condition in which ... sleep disorders and provide specific treatment for rapid eye movement sleep behavior disorder as well as obstructive sleep ...

  20. 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.

  1. 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. PMID:22029659

  2. 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. PMID:21633027

  3. Sporadic ALS/MND: a global neurodegeneration with retroviral involvement?

    PubMed

    Westarp, M E; Ferrante, P; Perron, H; Bartmann, P; Kornhuber, H H

    1995-05-01

    Sporadic amyotrophic lateral sclerosis may be an aetiologically heterogenous disease. We confirmed elevated circulating IgG immune complexes, and altered IgG seroreactivities against human retroviral antigens (HIV-2 and HTLV immunoblots) in overlapping subgroups of patients. Together with preliminary findings of a positive polymerase chain reactivity for human T-lymphotropic virus (HTLV.tax/rex) in blood leukocytes of 5 out of 14 sALS patients, we interpret this as evidence for a retroviral involvement in this relentlessly progressive, often asymmetrically spreading neurodegeneration. The possibility of a secondary phenomenon seems unlikely, yet cannot be completely ruled out. PMID:7595609

  4. 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. PMID:19328199

  5. Effect of trichostatin A on human T cells resembles signaling abnormalities in T cells of patients with systemic lupus erythematosus: a new mechanism for TCR zeta chain deficiency and abnormal signaling.

    PubMed

    Nambiar, Madhusoodana P; Warke, Vishal G; Fisher, Carolyn U; Tsokos, George C

    2002-01-01

    Trichostatin A (TSA) is a potent reversible inhibitor of histone deacetylase, and it has been reported to have variable effects on the expression of a number of genes. In this report, we show that TSA suppresses the expression of the T cell receptor zeta chain gene, whereas, it upregulates the expression if its homologous gene Fc(epsilon) receptor I gamma chain. These effects are associated with decreased intracytoplasmic-free calcium responses and altered tyrosine phosphorylation pattern of cytosolic proteins. Along with these effects, we report that TSA suppresses the expression of the interleukin-2 gene. The effects of TSA on human T cells are predominantly immunosuppressive and reminiscent of the signaling aberrations that have been described in patients with systemic lupus erythematosus. PMID:11967985

  6. The family resemblance metaphor: some unfinished business of interpretive inquiry.

    PubMed

    Miller, S I; Fredericks, M

    2000-07-01

    The rapidly expanding discipline of interpretive inquiry, especially in its narrative analysis form, has not been fully cognizant of certain crucial epistemological and methodological assumptions that form the ultimate basis of its purpose. Even after abandoning traditional positivist views, the related disciplines within the human sciences that are engaged in interpretive inquiry have still not discovered the core implicit assumptions that militate against a full acceptance of this form of inquiry. This article outlines the locus of these implicit assumptions and then argues that the legitimacy of these enterprises must be grounded in a well-known but heretofore undiscovered perspective, namely, Wittgenstein's notion of a family resemblance. It is argued that this metaphoric phrase is the key to unlocking the real and unique nature of narrative analysis. PMID:11010071

  7. Potential nosocomial acquisition of epidemic Listeria monocytogenes presenting as multiple brain abscesses resembling nocardiosis.

    PubMed

    Stefanovic, Aleksandra; Reid, James; Nadon, A Celine; Grant, Jennifer

    2010-01-01

    Listerial brain abscesses are rare, and are found mostly in patients with underlying hematological malignancies or solid-organ transplants. A case of a patient with Crohn's disease and multiple brain abscesses involving the left cerebellum and right sylvian fissure is described. The Gram stain and histopathology of the cerebellar abscess revealed Gram-positive, beaded rods suggestive of Nocardia. However, on culture, Listeria monocytogenes was identified. Listeria may appear Gram-variable and has been misidentified as streptococci, enterococci and diphtheroids. The present case is the first reported case of L monocytogenes resembling Nocardia on both microbiological and histopathological assessment. Reported cases of listerial brain abscesses are sporadic, while the current case was part of a nationwide listerial outbreak linked to consumption of contaminated deli meats. Broad antimicrobial therapy (including antilisterial coverage) in immunosuppressed patients presenting with brain abscess is crucial, until cultures confirm the identification of the organism. PMID:21358887

  8. Sporadic E-Layers and Meteor Activity

    NASA Astrophysics Data System (ADS)

    Alimov, Obid

    2016-07-01

    In average width it is difficult to explain variety of particularities of the behavior sporadic layer Es ionospheres without attraction long-lived metallic ion of the meteoric origin. Mass spectrometric measurements of ion composition using rockets indicate the presence of metal ions Fe+, Mg+, Si+, Na+, Ca+, K+, Al+ and others in the E-region of the ionosphere. The most common are the ions Fe+, Mg+, Si+, which are primarily concentrated in the narrow sporadic layers of the ionosphere at altitudes of 90-130 km. The entry of meteoric matter into the Earth's atmosphere is a source of meteor atoms (M) and ions (M +) that later, together with wind shear, produce midlatitude sporadic Es layer of the ionosphere. To establish the link between sporadic Es layer and meteoroid streams, we proceeded from the dependence of the ionization coefficient of meteors b on the velocity of meteor particles in different meteoroid streams. We investigated the dependence of the critical frequency f0Es of sporadic E on the particle velocity V of meteor streams and associations. It was established that the average values of f0Es are directly proportional to the velocity V of meteor streams and associations, with the correlation coefficient of 0.53 < R < 0.74. Thus, the critical frequency of the sporadic layer Es increases with the increase of particle velocity V in meteor streams, which indicates the direct influence of meteor particles on ionization of the lower ionosphere and formation of long-lived metal atoms M and ions M+ of meteoric origin.

  9. [Exploration of pathogenesis and therapy development for ALS employing sporadic disease model].

    PubMed

    Tanaka, Fumiaki; Waza, Masahiro; Yamamoto, Masahiko; Sobue, Gen

    2009-11-01

    The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remain poorly understood even now 140 years after the first description of the disease in 1869 by Jean-Martin Charcot. Exploration of pathogenesis of ALS has long been dependent on transgenic animal models with mutations in the copper/ zinc superoxide dismutase 1 (SOD1) gene. However, the lack of therapeutic concordance between these animal models and human sporadic ALS patients is troubling. The reasons include that there might exist the differences of pathogenesis between sporadic and familial ALS and/or the disease models for sporadic ALS have not been established. We have been working on screening motor neuron-specific genes critical for pathogenesis of sporadic ALS using cDNA microarray and laser capture microdissection techniques. Many of the resultant genes are of intense interest and may provide a powerful tool for determining the molecular mechanisms of sporadic ALS. In particular, dynactin-1, a major component of dynein/dynactin complex and several cell cycle-related genes are the targets of our research. Development and analysis of new disease models for sporadic ALS based on these genes will open an avenue for novel therapeutics. PMID:20030217

  10. Dissecting risk haplotypes in sporadic Alzheimer's disease.

    PubMed

    Soldner, Frank; Jaenisch, Rudolf

    2015-04-01

    Understanding how genetic risk variants contribute to complex diseases is crucial for predicting disease susceptibility and developing patient-tailored therapies. In this issue of Cell Stem Cell, Young et al. (2015) dissect the function of common non-coding risk haplotypes in the SORL1 locus in the pathogenesis of sporadic Alzheimer's disease using patient-derived induced pluripotent stem cells. PMID:25842969

  11. Canine neuroendocrine carcinoma. A tumor resembling histiocytoma.

    PubMed

    Nickoloff, B J; Hill, J; Weiss, L M

    1985-12-01

    The clinical and light- and electron microscopic features of 20 cases of canine neuroendocrine carcinoma, initially classified as atypical histiocytomas, are reported. The locally expansile well-circumscribed dermal tumor nodules were composed of solid masses of cells with high mitotic index and multinucleation, arranged in a trabecular pattern with prominent fibrovascular connective tissue stroma rich in reticulin fibers that outlined compact cell nests. Ultrastructural studies revealed evenly dispersed chromatin, focally indented nuclei and abundant cytoplasm with perinuclear filaments, membrane-bound dense core granules, and prominent interdigitating plasma membrane projections with primitive intercellular junctions. Clinical and pathological comparisons between canine neuroendocrine carcinoma, canine histiocytomas, and human Merkel cell neoplasms are discussed. PMID:4091229

  12. Islet1 deletion causes kidney agenesis and hydroureter resembling CAKUT.

    PubMed

    Kaku, Yusuke; Ohmori, Tomoko; Kudo, Kuniko; Fujimura, Sayoko; Suzuki, Kentaro; Evans, Sylvia M; Kawakami, Yasuhiko; Nishinakamura, Ryuichi

    2013-07-01

    Islet1 (Isl1) is a transcription factor transiently expressed in a subset of heart and limb progenitors. During studies of limb development, conditional Isl1 deletion produced unexpected kidney abnormalities. Here, we studied the renal expression of Isl1 and whether it has a role in kidney development. In situ hybridization revealed Isl1 expression in the mesenchymal cells surrounding the base of the ureteric bud in mice. Conditional deletion of Isl1 caused kidney agenesis or hypoplasia and hydroureter, a phenotype resembling human congenital anomalies of the kidney and urinary tract (CAKUT). The absence of Isl1 led to ectopic branching of the ureteric bud out from the nephric duct or to the formation of accessory buds, both of which could lead to obstruction of the ureter-bladder junction and consequent hydroureter. The abnormal elongation and poor branching of the ureteric buds were the likely causes of the kidney agenesis or hypoplasia. Furthermore, the lack of Isl1 reduced the expression of Bmp4, a gene implicated in the CAKUT-like phenotype, in the metanephric region before ureteric budding. In conclusion, Isl1 is essential for proper development of the kidney and ureter by repressing the aberrant formation of the ureteric bud. These observations call for further studies to investigate whether Isl1 may be a causative gene for human CAKUT. PMID:23641053

  13. Molecular pathogenesis of sporadic colorectal cancers.

    PubMed

    Yamagishi, Hidetsugu; Kuroda, Hajime; Imai, Yasuo; Hiraishi, Hideyuki

    2016-01-01

    Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classified into three major groups according to frequently altered/mutated genes. These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the first half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a limited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research field and discuss its prospects. PMID:26738600

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

    PubMed

    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

  15. 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

  16. 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.

  17. 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.

  18. Rocket observations of sporadic-E layers.

    NASA Technical Reports Server (NTRS)

    Smith, L. G.; Mechtly, E. A.

    1972-01-01

    The characteristics of midlatitude sporadic-E layers are observed using rocket payloads incorporating a probe and a propagation experiment. Layers below 120 km show evidence of preferred altitudes. The slopes of layers are within 1 deg of horizontal. The horizontal dimensions are deduced to be several hundred kilometers. Individual profiles of daytime layers show a range of shapes ranging from triangular to rectangular. The plasma frequency derived from the peak electron density in the layer is found to agree with the blanketing frequency given by the local ionosphere sounder.

  19. Sporadically Fractal Basin Boundaries of Chaotic Systems

    SciTech Connect

    Hunt, B.R.; Ott, E.; Rosa, E. Jr.

    1999-05-01

    We demonstrate a new type of basin boundary for typical chaotic dynamical systems. For the case of a two dimensional map, this boundary has the character of the graph of a function that is smooth and differentiable except on a set of fractal dimensions less than one. In spite of the basin boundary being smooth {open_quotes}almost everywhere,{close_quotes} its fractal dimension exceeds one (implying degradation of one{close_quote}s ability to predict the attractor an orbit approaches in the presence of small initial condition uncertainty). We call such a boundary {ital sporadically fractal}. {copyright} {ital 1999} {ital The American Physical Society}

  20. Early Detection of Sporadic Pancreatic Cancer

    PubMed Central

    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

    2015-01-01

    Abstract 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. PMID:25931254

  1. 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

  2. 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

  3. 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. PMID:26669818

  4. Toga-like virus as a cause of fulminant hepatitis attributed to sporadic non-A, non-B.

    PubMed

    Fagan, E A; Ellis, D S; Tovey, G M; Lloyd, G; Portmann, B; Williams, R; Zuckerman, A J

    1989-07-01

    Virus-like particles (60-70 nm) with spiked surfaces budding into cell vacuoles and rod-shaped inclusions were detected in nuclei of hepatocytes from a British patient transplanted for sporadic non-A, non-B fulminant hepatitis (NANB-FHF), probably contracted in Kenya. Identical particles were seen in two successive grafts (days 2 and 10) at regrafting for recurrent FHF. Ultrastructural features resembled those of the RNA-containing arbovirus, Rift Valley fever virus, but serological markers against a representative panel for arboviruses (Togaviruses) and transmission in mice proved negative. The particles shared features with the different arboviruses seen in the hepatectomy specimen of a second patient with NANB-FHF, and in both patients an insect vector was implicated in the clinical history. The particles were identical in size to those of a third patient with NANB-FHF, who had remained in the United Kingdom. These findings, together with the recent report of isolation of an RNA-containing virus resembling the Togaviridae, in parenteral NANB, suggest that several exotic virus-like agents resembling the arboviruses may be involved in the aetiology of NANB, including in the sporadic forms of FHF in the United Kingdom. PMID:2502604

  5. 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. PMID:25782705

  6. 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…

  7. Biomarkers for sporadic Creutzfeldt-Jakob disease.

    PubMed

    Soomro, Sanam; Mohan, Chandra

    2016-06-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare but fatal type of spongiform encephalopathy with unknown cause. Unfortunately, definitive diagnosis of this disease can only be done by examination of postmortem brain tissue. Presumptive diagnosis is done through a combination of clinical manifestations, radiology results, and cerebrospinal fluid (CSF) testing for CSF 14-3-3. Even with these guidelines, premortem diagnosis of sCJD can be unreliable with high rates of misdiagnosis. This calls for more reliable biomarkers of the disease, allowing for better diagnosis as well as understanding the pathogenesis of sCJD. This review compiles potential genetic, protein, biomolecular, and imaging biomarker studies for sCJD since 2010, highlighting the promise of proteins, cytokines, and composite biomarkers for improving the diagnosis as well as understanding the pathogenesis of this mysterious ailment. PMID:27547775

  8. 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.

  9. 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.

  10. Carbonaceous objects resembling nannobacteria in the Allende meteorite

    NASA Astrophysics Data System (ADS)

    Folk, Robert L.; Lynch, F. Leo

    1998-07-01

    The carbon in Allende consists of balls ranging form 30 to 150 nm in diameter.Most are spheres, but some ovoid to worm- like forms occur. Grape-like clumps and rosary-like chains are the most dramatic mimics of terrestrial bacterial colonies. We propose that the carbon balls in Allende represent roasted corpses of nanobacteria because of their resemblance to nanobacteria on earth.

  11. Steroid Dermatitis Resembling Rosacea: A Clinical Evaluation of 75 Patients

    PubMed Central

    Hameed, Ammar F.

    2013-01-01

    Background. The use of topical steroids on the skin of the face should be carefully evaluated by the dermatologist; however, its misuse still occurs producing dermatological problem resembling rosacea. Objectives. To report the different clinical manifestations of steroid dermatitis resembling rosacea and to discover causes behind abusing topical steroids on the face. Methods. In this prospective observational study, 75 patients with steroid dermatitis resembling rosacea who had history of topical steroid use on their faces for at least 1–3 months were evaluated at the Department of Dermatology, Baghdad Teaching Hospital, between August 2010 and December 2012. Results. The majority of patients were young women who used a combinations of potent and very potent topical steroid for average period of 0.25–10 years. Facial redness and hotness, telangiectasia, and rebound phenomenon with papulopustular eruption were the main clinical presentations. The most common causes of using topical steroid on the face were pigmentary problems and acne through recommendations from nonmedical personnel. Conclusion. Topical steroid should not be used on the face unless it is under strict dermatological supervision. PMID:23691345

  12. 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

  13. 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.

  14. Treatment of Sporadic Acute Puerperal Mastitis

    PubMed Central

    Barton, John R.

    1996-01-01

    Objective: The purposes of this study were to compare the efficacy of amoxicillin and cephradine for the treatment of sporadic acute puerperal mastitis (SAPM) and to evaluate the microbiology and clinical parameters of this infection. Methods: We conducted a prospective, randomized, single-blinded study comparing amoxicillin, 500 mg orally q 8 h for 7 days, and cephradine, 500 mg orally q 6 h for 7 days. The diagnostic criteria for SAPM included a temperature of ≥37.56℃ (≥99.6℉) and erythema and tenderness of the breast(s). Results: Twenty-seven consecutive outpatients with SAPM were evaluated for admission to the study, and 25 of these were enrolled. The mean temperature at enrollment was 38.17℃ (100.7℉), with a mean WBC count of 11,440/μl. The most frequent bacterial isolates from expressed milk were Staphylococcus aureus (7), staphylococcal species (coagulase negative) (8), and α-hemolytic streptococci (4). There were no significant differences between the 2 antibiotic regimens in cure rate, mean days to resolution of symptoms, or recurrence within 30 days. Both of the treatment failures and 1 of the 3 recurrences within 30 days were amoxicillin-treated patients whose cultures grew S. aureus. Conclusions: Oral amoxicillin and cephradine appear equally effective in the treatment of SAPM. Staphylococci were the most frequent isolates from the milk of women with mastitis. PMID:18476075

  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. Sporadic hyperekplexia presenting with an ataxic gait.

    PubMed

    Rouco, Idoia; Bilbao, Iker; Losada, Jose; Maestro, Iratxe; Zarranz, Juan Jose

    2014-02-01

    We describe a 62-year-old man with a sporadic form of hyperekplexia who presented with an unsteady gait, present since the age of 47. His clinical examination revealed an insecure broad-based gait and difficulty with tandem walking but no other abnormalities. For nearly a decade the patient was misdiagnosed with an idiopathic ataxia. A video electroencephalogram combined with an electromyogram during sudden auditory stimulus demonstrated an excessive startle response. An extensive work-up ruled out all the known causes of symptomatic hyperekplexia including anti-glycine receptor antibodies. Treatment with clonazepam markedly reduced the threshold and intensity of the startle response, enabling him to recover independence. Hyperekplexia is frequently associated with an awkward and hesitating gait, but these gait abnormalities might be confused with other causes of gait disorders if one is not aware of this disease. We report this patient to highlight that a correct diagnosis of hyperekplexia is crucial, because its treatment may change quality of life. PMID:24054400

  17. Molecular Karyotype of Sporadic Unilateral Retinoblastoma Tumors

    PubMed Central

    Ganguly, Arupa; Nichols, Kim E.; Grant, Gregory; Rappaport, Eric; Shields, Carol

    2009-01-01

    Background Retinoblastoma (RB) is a childhood ocular malignancy associated with mutations in RB1, a tumor susceptibility gene. Inactivation of both copies of the RB1 gene in a retinal cell is followed by the sequential acquisition of additional genetic changes that define the course to tumor formation. Methods To identify the genetic events that cooperate with loss of the RB1 gene function, we performed a whole genome sampling assay (WGSA) based on SNP genotyping. We used DNA isolated from 25 sporadic, unilateral RB tumors and matched blood samples. Results Genomic profiles were analyzed to identify regions of loss of heterozygosity (LOH) and/or amplification. Two major subclasses of RB tumors were defined by the presence (n=18) or absence (n=7) of LOH of chromosome 13. LOH in most cases was due to copy neutral events caused by mitotic recombination and mitotic non-disjunction. Tumors harbored novel regions of amplification at 1q44, 3p25, 11q14, 11q25, 14q23, 15q21, 16p13, 17p11.2, 19q13, and 20q13 while regions of loss included 6q22, 7q21and 21q2. Conclusion WGSA-based analysis of unilateral RB tumors revealed novel regions as significant. These minimum critical regions that are lost or amplified are expected to harbor genes that aid the process of tumorigenesis. PMID:19491728

  18. 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

  19. 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. PMID:27103865

  20. Interleukin-21 sustains inflammatory signals that contribute to sporadic colon tumorigenesis

    PubMed Central

    De Simone, Veronica; Ronchetti, Giulia; Franzè, Eleonora; Colantoni, Alfredo; Ortenzi, Angela; Fantini, Massimo C.; Rizzo, Angelamaria; Sica, Giuseppe S.; Sileri, Pierpaolo; Rossi, Piero; MacDonald, Thomas T.; Pallone, Francesco; Monteleone, Giovanni; Stolfi, Carmine

    2015-01-01

    Interleukin (IL)-21 triggers inflammatory signals that contribute to the growth of neoplastic cells in mouse models of colitis-associated colorectal cancer (CRC). Because most CRCs are sporadic and arise in the absence of overt inflammation we have investigated the role of IL-21 in these tumors in mouse and man. IL-21 was highly expressed in human sporadic CRC and produced mostly by IFN-γ-expressing T-bet/RORγt double-positive CD3+CD8− cells. Stimulation of human CRC cell lines with IL-21 did not directly activate the oncogenic transcription factors STAT3 and NF-kB and did not affect CRC cell proliferation and survival. In contrast, IL-21 modulated the production of protumorigenic factors by human tumor infiltrating T cells. IL-21 was upregulated in the neoplastic areas, as compared with non-tumor mucosa, of Apcmin/+ mice, and genetic ablation of IL-21 in such mice resulted in a marked decrease of both tumor incidence and size. IL-21 deficiency was associated with reduced STAT3/NF-kB activation in both immune cells and neoplastic cells, diminished synthesis of protumorigenic cytokines (that is, IL-17A, IL-22, TNF-α and IL-6), downregulation of COX-2/PGE2 pathway and decreased angiogenesis in the lesions of Apcmin/+ mice. Altogether, data suggest that IL-21 promotes a protumorigenic inflammatory circuit that ultimately sustains the development of sporadic CRC. PMID:25839161

  1. Mutational analysis of the thyrotropin receptor gene in sporadic and familial feline thyrotoxicosis.

    PubMed

    Pearce, S H; Foster, D J; Imrie, H; Myerscough, N; Beckett, G J; Thoday, K L; Kendall-Taylor, P

    1997-12-01

    The characterization of a spontaneous animal model equivalent to a human form of thyrotoxicosis would provide a useful resource for the investigation of the human disorder. Feline thyrotoxicosis is the only common form of hyperthyroidism found in domestic or laboratory animals, but its etiopathogenesis remains poorly defined. We have used the polymerase chain reaction (PCR) to amplify codons 480-640 of the previously uncharacterized feline thyrotropin receptor (TSHR) gene, and have determined the DNA sequence in this transmembrane domain region. We have analyzed single stranded conformational polymorphisms in thyroid DNA from 11 sporadic cases of feline thyrotoxicosis and leukocyte DNA from two cases of familial feline thyrotoxicosis. We have also determined the DNA sequence of this region of the TSHR in five of the cases of sporadic feline thyrotoxicosis and the two familial thyrotoxic cats. The normal feline TSHR sequence between codons 480-640 is highly homologous to that of other mammalian TSHRs, with 95%, 92%, and 90% amino acid identity between the feline receptor and canine, human, and bovine TSHRs, respectively. Thyroid gland DNA from 11 cats with sporadic thyrotoxicosis did not have mutations in this region of the TSHR gene. Leukocyte DNA from two littermates with familial feline thyrotoxicosis did not harbor mutations of this region of the TSHR gene. These studies suggest that TSHR gene mutations are not a common cause of feline thyrotoxicosis. PMID:9459639

  2. Sequence of retrovirus provirus resembles that of bacterial transposable elements

    NASA Astrophysics Data System (ADS)

    Shimotohno, Kunitada; Mizutani, Satoshi; Temin, Howard M.

    1980-06-01

    The nucleotide sequences of the terminal regions of an infectious integrated retrovirus cloned in the modified λ phage cloning vector Charon 4A have been elucidated. There is a 569-base pair direct repeat at both ends of the viral DNA. The cell-virus junctions at each end consist of a 5-base pair direct repeat of cell DNA next to a 3-base pair inverted repeat of viral DNA. This structure resembles that of a transposable element and is consistent with the protovirus hypothesis that retroviruses evolved from the cell genome.

  3. Carisoprodol withdrawal syndrome resembling neuroleptic malignant syndrome: Diagnostic dilemma

    PubMed Central

    Paul, Gunchan; Parshotam, Gautam L; Garg, Rajneesh

    2016-01-01

    Soma (Carisoprodol) is N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; a commonly prescribed, centrally acting skeletal muscle relaxant. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of antipsychotic agents. Although diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated, may be warranted. We wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol (Soma) withdrawal resembling NMS that was a diagnostic dilemma. Subsequently, it was successfully treated with oral baclofen in absence of sodium dantrolene.

  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. Tocilizumab infusion therapy normalizes inflammation in sporadic ALS patients

    PubMed Central

    Fiala, Milan; Mizwicki, Mathew T; Weitzman, Rachel; Magpantay, Larry; Nishimoto, Norihiro

    2013-01-01

    Patients with sporadic amyotrophic lateral sclerosis (sALS) show inflammation in the spinal cord and peripheral blood. The inflammation is driven by stimulation of macrophages by aggregated superoxide dismutase 1 (SOD1) through caspase1, interleukin 1 (IL1), IL6 and chemokine signaling. Inflammatory gene activation is inhibited in vitro by tocilizumab, a humanized antibody to IL6 receptor (IL6R). Tocilizumab inhibits global interleukin-6 (IL6) signaling, a key mechanism in chronic rheumatoid disorders. Here we studied in vivo baseline inflammatory gene transcription in peripheral blood mononuclear cells (PBMCs) of 10 sALS patients, and the effects of tocilizumab (ActemraR) infusions. At baseline, one half of ALS subjects had strong inflammatory activation (Group 1) (8 genes up regulated >4-fold, P<0.05 vs. controls) and the other half (Group 2) had weak activation. All patients showed greater than four-fold up regulation of MMP1, CCL7, CCL13 and CCL24. Tocilizumab infusions in the Group 1 patients resulted in down regulation of inflammatory genes (in particular IL1β), whereas in the Group 2 patients in up regulation of inflammatory genes. Post-infusion serum and CSF concentrations of tocilizumab inhibited caspase1 activation in vitro. Three of 5 patients receiving tocilizumab infusions showed time-limited attenuation of clinical progression. In conclusion, inflammation of sALS patients at baseline is up- or down-regulated in comparison to controls, but is partially normalized by tocilizumab infusions. PMID:23844337

  6. 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

  7. 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

  8. Joint observations of sporadic sodium and sporadic E layers at middle and low latitude in China

    NASA Astrophysics Data System (ADS)

    Yang, Guotao; Wang, Jihong; Du, Lifang; Yue, Chuan; Wang, Zelong; Jiao, MS. Jing

    The sporadic sodium layers (SSL) phenomena were studied with sodium (Na) lidar at Beijing (40. 5°N,116. 0°E) and Haikou (19.5°N, 109.1°E) in China. The main parameters of SSL and Es events were statistically analyzed at both observing sites. SSL occurrence has maximum near 22:00 LT, and Es occurrence has maximum before midnight. Comparison reveals that all the average values of height and strength factor of SSL and Es at Beijing are higher than those at Haikou, as well as the average of foEs. The correlation of SSL with Es is stronger at Haikou, and the formation of SSL is obviously influenced by seasonally varied chemical and dynamical processes.

  9. The Cybrid Model of Sporadic Parkinson’s Disease

    PubMed Central

    Trimmer, Patricia A.; Bennett, James P.

    2009-01-01

    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 (~90%) is sporadic (sPD), is associated with mitochondrial deficiencies and has been studied in cell and animal models arising from 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 mtDNA’s 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-infrered 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 use of non-tumor human stem cell-derived neural precursor cells and by introduction of postmortem brain mtDNA to test its causality directly. PMID:19328199

  10. Two-hit model for sporadic congenital anomalies in mice with the disorganization mutation

    SciTech Connect

    Crosby, J.L. Univ. of Maine, Orono Vanderbilt Univ. School of Medicine, Nashville, TN ); Varnum, D.S.; Nadeau, J.H. )

    1993-05-01

    Congenital anomalies have complex etiologies involving both genetic and nongenetic components. Many are sporadic, without obvious evidence for heritability. An important model for these anomalies is a mutation in laboratory mice that is called [open quotes]disorganization[close quotes] (Ds), which functions as a variable autosomal dominant and leads to a wide variety of congenital anomalies involving many developmental processes and systems. Variable expressivity, asymmetrical manifestations, and low penetrance suggest that somatic events determine the location and nature of these anomalies. A statistical analysis suggests that occurrence of anomalies in mice with the Ds mutation follows a Poisson distribution. These results suggest that congenital anomalies in mice with the Ds mutation occur independently of each other. The authors propose that Ds causes a heritable predisposition to congenital anomalies and that Ds and appropriate somatic events combine to compromise normal development. They also propose that some sporadic, nonheritable congenital anomalies involve somatic mutations at Ds-like loci. Ds may therefore serve not only as a model for developmental anomalies in cell fate and pattern formation but also for complex developmental traits showing variable expressivity, low penetrance, and sporadic occurrence in mice and humans. 58 refs., 2 figs., 1 tab.

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

    PubMed

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

    2016-02-15

    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

  12. 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. PMID:26647307

  13. 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

  14. Tramadol Use in Premature Ejaculation: Daily Versus Sporadic Treatment

    PubMed Central

    Khan, Amil H.; Rasaily, Deepa

    2013-01-01

    Aim: Premature ejaculation (PME) is defined as ejaculation with the minimal sexual stimulation before, on or shortly after penetration and or before a person wishes it. It is a function of the time between intra-vaginal penetration and intra-vaginal ejaculation. Tramadol has shown efficacy in PME when used as sporadic basis. In this study, we compared the use of 100 mg of tramadol as sporadic treatment (administered 6-8 h before coitus) versus continued treatment with the objective of evaluating the therapeutic results of both modalities. We assumed our alternative hypothesis that they have similar effects. Materials and Methods: A prospective study was carried out on 60 patients divided into two groups of 30 patients each. Intra-vaginal ejaculation latency time (IELT) and coital frequency were measured both prior to and after the treatment. Group A received tramadol 100 mg daily for 4 weeks and on request (sporadically) for 4 weeks more. Group B was given placebo in the same manner. Results were statistically analyzed using the Student t-test. Results: Mean IELT prior to treatment was 59.2 s in Group A and 58.7 s in Group B. Mean pre-treatment coital frequency was 2.44 times/week for Group A and 2.13 times/week for Group B. Mean IELT was 202.5 s after continued tramadol treatment and 238.2 s after sporadic treatment in Group A. Mean IELT with daily placebo was 94.8 s and with sporadic placebo was 96.6 s. Coital frequency increased to 4.32 times/week with daily tramadol treatment and 4.86 times with sporadic treatment. Coital frequency increased to 2.88 times/week with daily placebo treatment and 3.23 times with sporadic treatment. Conclusions: The results of PME treatment with tramadol are similar with both continued and sporadic administration. The sex life of patients improved and they reported greater satisfaction with the sporadic treatment. PMID:24249927

  15. 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.

  16. Musculoskeletal Hydatid Cysts Resembling Tumors: A Report of Five Cases.

    PubMed

    Toğral, Güray; Arıkan, Şefik M; Ekiz, Timur; Kekeç, Ahmet F; Ekşioğlu, Mehmet F

    2016-05-01

    Although challenges in treatment of musculoskeletal hydatid cysts (HC) lesions have been documented, data regarding the musculoskeletal HC lesions resembling tumor is scarce. This paper presented 5 patients (3 males, 2 females) with a mean age of 41.6 years with tumor-like lesions of HC. Three of them had left ilium and acetabulum involvement, one involved left femur, and one involved left thigh muscle compartments. Pain was the main symptom and was seen in all patients. Clinical examination, radiologic evaluation, and histologic analysis were performed for diagnosis. Patients were treated through different surgical options, including simple debridement, bone cement filling with or without internal fixation, hip arthrodesis, reconstruction using hemipelvic replantation with femoral prosthesis and distal femur endoprosthetic replacement. After surgery, the operation region was washed by 20% hypertonic saline, and debridement was performed carefully without contamination. All patients received albendazole treatment. Cases were followed up 1 to 9 years for the recurrence. Walking difficulty and pain were the main symptoms during the follow-up. One patient was symptom-free. A reoccurrence in the perioperative soft tissue was detected in only one patient and control visits with antihelmintic treatment were recommended. We would like to emphasize that HC should be kept in mind for the differential diagnosis of the cystic or tumoral lesions of the musculoskeletal system, particularly in the endemic regions. Prompt diagnosis is of paramount importance for preventing destruction and complications. PMID:27384735

  17. Case of Young-Onset Sporadic Amyotrophic Lateral Sclerosis.

    PubMed

    Artemiadis, Artemios K; Peppas, Christos; Giannopoulos, Sotiris; Zouvelou, Vasiliki; Triantafyllou, Nikos

    2016-06-01

    Amyotrophic lateral sclerosis (ALS) constitutes the main type of motor neuron disease. Familial ALS is characterized by the presence of positive family history and accounts for 10% of ALS cases. Although familial ALS is the main culprit for early-onset disease, there are rare cases of early- or young-onset ALS with negative family history or sporadic ALS. We describe a 23-year-old man with clinical and electrophysiological evidence of probable sporadic ALS according to the revised EI Escorial criteria. Interestingly, brain neuroimaging revealed bilaterally increased T2 signals across corona radiata, posterior limb of the internal capsule, and descending motor tracts in the brainstem and hypointensity rim of the motor cortex on T2-weighted images. Young-onset sporadic ALS may be a distinct nosological entity. The topic is shortly discussed in the light of its genetic and clinical characteristics. PMID:27224438

  18. 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.

  19. RECQL4 helicase has oncogenic potential in sporadic breast cancers.

    PubMed

    Arora, Arvind; Agarwal, Devika; Abdel-Fatah, Tarek Ma; Lu, Huiming; Croteau, Deborah L; Moseley, Paul; Aleskandarany, Mohammed A; Green, Andrew R; Ball, Graham; Rakha, Emad A; Chan, Stephen Yt; Ellis, Ian O; Wang, Lisa L; Zhao, Yongliang; Balajee, Adayabalam S; Bohr, Vilhelm A; Madhusudan, Srinivasan

    2016-03-01

    RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund-Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer predisposition. RECQL4 is widely considered to be a tumour suppressor, although its role in human breast cancer is largely unknown. As the RECQL4 gene is localized to chromosome 8q24, a site frequently amplified in sporadic breast cancers, we hypothesized that it may play an oncogenic role in breast tumourigenesis. To address this, we analysed large cohorts for gene copy number changes (n = 1977), mRNA expression (n = 1977) and protein level (n = 1902). Breast cancer incidence was also explored in 58 patients with type II RTS. DNA replication dynamics and chemosensitivity was evaluated in RECQL4-depleted breast cancer cells in vitro. Amplification or gain in gene copy number (30.6%), high-level mRNA expression (51%) and high levels of protein (23%) significantly associated with aggressive tumour behaviour, including lymph node positivity, larger tumour size, HER2 overexpression, ER-negativity, triple-negative phenotypes and poor survival. RECQL4 depletion impaired the DNA replication rate and increased chemosensitivity in cultured breast cancer cells. Thus, although recognized as a 'safe guardian of the genome', our data provide compelling evidence that RECQL4 is tumour promoting in established breast cancers. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26690729

  20. The excitation of plasma lines in blanketing sporadic E

    NASA Technical Reports Server (NTRS)

    Gordon, W. E.; Carlson, H. C.

    1976-01-01

    Enhanced plasma lines in blanketing sporadic E have been excited by a powerful HF radio wave illuminating the E region over the Arecibo Observatory. The plasma lines are observed by the incoherent scatter radar at the observatory. They originate in the sporadic E layer when the blanketing frequency exceeds the exciting frequency, a result which confirms that the plasma is overdense for the exciting frequency. Around the time when the blanketing frequency falls through the exciting frequency, large fluctuations in the plasma line intensities are observed, and thus the possibility of overdense patches drifting through the sampled volume is suggested.

  1. 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

  2. Sporadic case of listeriosis associated with the consumption of a Listeria monocytogenes-contaminated 'Camembert' cheese.

    PubMed

    Gilot, P; Hermans, C; Yde, M; Gigi, J; Janssens, M; Genicot, A; André, P; Wauters, G

    1997-09-01

    Listeria monocytogenes is an intracellular gram-positive organism responsible for severe infections in both humans and animals. Whereas the food-borne transmission of listeriosis was demonstrated in several outbreaks, most cases of listeriosis occur sporadically and are rarely linked with consumption of contaminated foods. In this paper a case of septicaemia with L. monocytogenes in a 73-year-old immunocompromised man is described. Evidence for the association of this case of listeriosis with the consumption of a contaminated 'Camembert' cheese is provided by serotyping, esterase typing, DNA macrorestriction patterns analysis and level of virulence of the isolated strains for mice. PMID:9354360

  3. Paired box mutations in familial and sporadic aniridia predicts truncated aniridia proteins.

    PubMed Central

    Martha, A.; Ferrell, R. E.; Mintz-Hittner, H.; Lyons, L. A.; Saunders, G. F.

    1994-01-01

    Aniridia, an autosomal dominant ocular disorder characterized by iris hypoplasia, results from mutations in the PAX6 gene, which encodes paired box and homeobox motifs. In this report we describe five new mutations in the paired box region of the human PAX6 gene that are associated with aniridia. The paired box mutations that we detected were in both familial (three) and sporadic (two) cases. All five mutations predict truncated PAX6 proteins. Our study indicates that early premature translational termination mutations in the PAX6 gene result in haploinsufficiency and generate the aniridia phenotype. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:7909985

  4. Impaired proteasome function in sporadic amyotrophic lateral sclerosis.

    PubMed

    Kabashi, Edor; Agar, Jeffrey N; Strong, Michael J; Durham, Heather D

    2012-06-01

    Abstract The ubiquitin-proteasome system, important for maintaining protein quality control, is compromised in experimental models of familial ALS. The objective of this study was to determine if proteasome function is impaired in sporadic ALS. Proteasomal activities and subunit composition were evaluated in homogenates of spinal cord samples obtained at autopsy from sporadic ALS and non-neurological control cases, compared to cerebellum as a clinically spared tissue. The level of 20S α structural proteasome subunits was assessed in motor neurons by immunohistochemistry. Catalysis of peptide substrates of the three major proteasomal activities was substantially reduced in ALS thoracic spinal cord, but not in cerebellum, accompanied by alterations in the constitutive proteasome machinery. Chymotrypsin-like activity was decreased to 60% and 65% of control in ventral and dorsal spinal cord, respectively, concomitant with reduction in the β5 subunit with this catalytic activity. Caspase- and trypsin-like activities were reduced to a similar extent (46% - 68% of control). Proteasome levels, although generally maintained, appeared reduced specifically in motor neurons by immunolabelling. In conclusion, there are commonalities of findings in sporadic ALS patients and presymptomatic SOD1-G93A transgenic mice and these implicate inadequate proteasome function in the pathogenesis of both familial and sporadic ALS. PMID:22632443

  5. 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

  6. Facial resemblance to emotions: group differences, impression effects, and race stereotypes.

    PubMed

    Zebrowitz, Leslie A; Kikuchi, Masako; Fellous, Jean-Marc

    2010-02-01

    The authors used connectionist modeling to extend previous research on emotion overgeneralization effects. Study 1 demonstrated that neutral expression male faces objectively resemble angry expressions more than female faces do, female faces objectively resemble surprise expressions more than male faces do, White faces objectively resemble angry expressions more than Black or Korean faces do, and Black faces objectively resemble happy and surprise expressions more than White faces do. Study 2 demonstrated that objective resemblance to emotion expressions influences trait impressions even when statistically controlling possible confounding influences of attractiveness and babyfaceness. It further demonstrated that emotion overgeneralization is moderated by face race and that racial differences in emotion resemblance contribute to White perceivers' stereotypes of Blacks and Asians. These results suggest that intergroup relations may be strained not only by cultural stereotypes but also by adaptive responses to emotion expressions that are overgeneralized to groups whose faces subtly resemble particular emotions. PMID:20085393

  7. Pathological features of proteinuric nephropathy resembling Alport syndrome in a young Pyrenean Mountain dog

    PubMed Central

    SUGAHARA, Go; NAITO, Ichiro; MIYAGAWA, Yuichi; KOMIYAMA, Takaaki; TAKEMURA, Naoyuki; KOBAYASHI, Ryosuke; MINESHIGE, Takayuki; KAMIIE, Junichi; SHIROTA, Kinji

    2015-01-01

    The renal biopsy tissue from a 9-month-old, male Pyrenean Mountain dog with renal disorder and severe proteinuria was examined. Ultrastructural examination revealed multilaminar splitting and fragmentation of the glomerular basement membrane (GBM) and diffuse podocyte foot process effacement. Immunofluorescent staining for α(IV) chains revealed presence of α5(IV) and complete absence of α3(IV) and α4(IV) chains in the GBM. Immunohistochemistry also revealed decreased and altered expression of nephrin and podocin in the glomeruli compared with normal canine glomeruli. These results suggested that the glomerular disease of the present case might be consistent with canine hereditary nephropathy resembling human Alport syndrome caused by genetic defect of type IV collagen, and indicated possible contribution of podocyte injury to severe proteinuria in this case. PMID:25892536

  8. Anastellin, an FN3 Fragment with Fibronectin Polymerization Activity, Resembles Amyloid Fibril Precursors

    SciTech Connect

    Briknarova, Klara; Akermann, Maria; Hoyt, David W. ); Ruoslahti, Erkki; Ely, Kathryn R.

    2003-08-01

    Anastellin is a carboxy-terminal fragment of the 1st FN3 domain from human fibronectin. It is capable of polymerizing fibronectin in vitro, and it displays anti-tumor, antimetastatic and anti-angiogenic properties in vivo. We have determined the structure of anastellin using nuclear magnetic resonance spectroscopy and identified residues critical for its activity. Anastellin exhibits dynamic fluctuations and conformational exchange in solution. Its overall topology is very similar to the corresponding region of full-length FN3 domains. However, its hydrophobic core becomes solvent accessible and some of its -strands lose their protection against hydrogen bonding to -strands from other molecules. These features seem to be relevant for the fibronectin polymerization activity of anastellin and resemble the characteristics of amyloid fibril precursors. We suggest that this analogy is not random and may reflect similarities between fibronectin and amyloid fibril formation.

  9. Positive 14-3-3 and tau proteins in a sporadic Creutzfeldt-Jakob disease case and a brief perspective of prion diseases in Colombia.

    PubMed

    Escandón-Vargas, Kevin; Zorrilla-Vaca, Andrés; Corral-Prado, Raúl Heli

    2016-01-01

    Prion diseases are rare neurodegenerative disorders occurring worldwide and affecting both humans and animals. Herein, we present the case of a patient diagnosed with definite sporadic Creutzfeldt-Jakob disease in Cali, Colombia. Besides neurological examination, 14-3-3 and tau proteins were valuable tools supporting the diagnosis. We also present a brief perspective of the prion diseases reported in Colombia to date. Although the incidence of prion diseases is unknown in Colombia, our literature review revealed that one case of scrapie in 1981 and 29 human sporadic cases of Creutzfeldt-Jakob disease have been documented and published in our country. PMID:27622622

  10. Visual kin recognition and family resemblance in chimpanzees (Pan troglodytes).

    PubMed

    Vokey, John R; Rendall, Drew; Tangen, Jason M; Parr, Lisa A; de Waal, Frans B M

    2004-06-01

    The male-offspring biased visual kin recognition in chimpanzees (Pan troglodytes) reported by L. A. Parr and F. B. M. de Waal (1999) was replicated with human (Homo sapiens) participants and a principal components analysis (PCA) of pixel maps of the chimpanzee face photos. With the same original materials and methods, both humans and the PCA produced the same asymmetry in kin recognition as found with the chimpanzees. The PCA suggested that the asymmetry was a function of differences in the distribution of global characteristics associated with the framing of the faces in the son and daughter test sets. Eliminating potential framing biases, either by cropping the photos tightly to the faces or by rebalancing the recognition foils, eliminated the asymmetry but not human participants' ability to recognize chimpanzee kin. PMID:15250806

  11. Role of Poultry Meat in Sporadic Campylobacter Infections in Bosnia and Herzegovina: Laboratory-based Study

    PubMed Central

    Uzunović-Kamberović, Selma; Zorman, Tina; Heyndrickx, Marc; Smole Možina, Sonja

    2007-01-01

    Aim To investigate genetic diversity and specificity of Campylobacter jejuni and Campylobacter coli strains isolated from humans, retail poultry meat, and live farm chickens in Zenica-Doboj Canton, Bosnia and Herzegovina, and identify the role of poultry meat in sporadic Campylobacter infections. Methods We determined the type of Campylobacter species using standard microbiological methods and multiplex polymerase chain reaction (PCR), and performed pulsed field gel-electrophoresis (PFGE) and restriction fragment length polymorphism (RFLP) typing of the flaA gene to investigate genetic diversity among the isolates. Results We isolated C jejuni and C coli from 75 (5.2%) of 1453 samples of consecutive outpatients with sporadic diarrhea; from 51 (34.7%) of 147 samples of poultry meat; and from 15 out of 23 farm chicken samples. The proportion of C coli found among human (30.1%), poultry meat (56.9%), and farm chicken isolates (53.3%), was greater than the proportion of C jejuni. Fourteen and 24 PFGE genotypes were identified among 20 C coli and 37 C jejuni isolates, respectively. Identical PFGE genotypes were found in two cases of human and poultry meat isolates and two cases of poultry meat and farm chicken isolates. Conclusion Only a minority of human Campylobacter isolates shared identical PFGE type with poultry meat isolates. Although poultry is the source of a certain number of human infections, there may be other more important sources. Further research is required to identify the environmental reservoir of Campylobacter spp responsible for causing human disease and the reason for the high prevalence of C coli human infections in this region. PMID:18074419

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

    PubMed Central

    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.

    2015-01-01

    Summary 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. PMID:26137419

  13. Loss of WIF-1 and Wnt5a expression is related to aggressiveness of sporadic breast cancer in Tunisian patients.

    PubMed

    Trifa, Fatma; Karray-Chouayekh, Sondes; Jmal, Emna; Jmaa, Zeineb Ben; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

    2013-06-01

    Activation of the Wnt/β-catenin signaling pathway is common in various human cancers. The aim of this study was to investigate the expression of 2 members of the Wnt family (WIF-1 and Wnt5a) in sporadic and hereditary breast cancer tissues. WIF-1, is a secreted antagonist that binds Wnt ligands, and therefore inhibits the canonical Wnt/β-catenin pathway. Wnt5a is one of the members of the noncanonical Wnt family that mainly acts through calcium signaling pathway. The expression of WIF-1 was analyzed by methylation-specific PCR and RT-PCR, and the level of Wnt5a ligand was quantified by RT-QPCR in breast cancer tissues. Methylation of WIF-1 was detected in 71.3 % and 81.8 % of sporadic and hereditary cases, respectively. Aberrant methylation of WIF-1 was associated with advanced TNM stage and triple negative cases in sporadic breast carcinoma (p=0.001 and p=0.037, respectively). In hereditary cases, methylation of WIF-1 correlated with age at diagnosis (p=0.027) and p53 status (p=0.035). Regarding patients' survival, WIF-1 methylated promoter conferred a reduced overall survival rate, and particularly in a group of patients with advanced TNM stage (p log rank=0.006). Furthermore, aberrant CpG methylation of the WIF-1 promoter was significantly associated with transcriptional silencing of this tumor suppressor gene in sporadic breast cancer tissues (p=0.036). On the other hand, in sporadic tumor tissues, the level of Wnt5a mRNA was significantly lower compared to normal tissues (p=0.031) and lower still in those showing more aggressive behavior, suggesting that Wnt5a, a ligand involved in the noncanonical Wnt/β-catenin pathway, could act as a tumor suppressor gene in breast cancer. PMID:23417837

  14. Disseminated eosinophilic disease resembling idiopathic hypereosinophilic syndrome in a dog.

    PubMed

    Aroch, I; Perl, S; Markovics, A

    2001-09-29

    True idiopathic hypereosinophilic syndrome has been described in human beings and cats, but not in dogs. The syndrome is characterised by prolonged unexplained peripheral mature eosinophilia, the infiltration of many organs by eosinophils, organ dysfunction and a fatal outcome. This paper describes an idiopathic disseminated eosinophilic disease in a dog involving various organs, manly the heart and the lungs, accompanied by a leukemoid eosinophilic response, and a fatal outcome. The histopathological findings included the infiltration of the myocardium, lung parenchyma, liver, spleen, lymph nodes and skeletal muscles with eosiniphils. PMID:11601516

  15. Segregation and sporadic cases in families with Hunter's syndrome.

    PubMed Central

    Machill, G; Barbujani, G; Danieli, G A; Herrmann, F H

    1991-01-01

    Segregation analysis on five samples of families with Hunter's syndrome (158 cases overall) shows that the mutant allele segregates in agreement with Mendelian expectations for an X linked recessive disease, but the proportion of sporadic cases is significantly lower than expected under mutation-selection equilibrium. Heterogeneity among the samples is apparent, but it is caused entirely by a sample of Ashkenazi families, whose segregation pattern has previously been interpreted as supporting the hypothesis of prenatal selection in favour of the pathological allele. Conversely, our joint analysis of the five samples by a maximum likelihood approach does not suggest segregation distortion. Possible reasons for the apparent lack of sporadic cases include the effect of ascertainment bias. PMID:1908009

  16. On permanent and sporadic pulsations of the magnetosphere

    NASA Astrophysics Data System (ADS)

    Guglielmi, A. V.

    2015-05-01

    A question concerning the influence of permanent Pc3-band pulsations (periods from 10 to 45 s) on the excitation of sporadic Pi2-band pulsations (40 to 150 s) is raised. It is hypothesized that, being generated ahead of the front of the Earth's magnetosphere, the Pc3 penetrate into the geomagnetic tail where they cause local depression in the electric current in the neutral sheet and, under favorable conditions, initiate tearing instability. This leads to the reconnection of the magnetic field lines and explosion-like release of the magnetic energy stored in the tail. As a result, a substorm arises with the sporadic Pi2 pulsations being its important element. Ways are suggested to theoretically substantiate and experimentally validate this hypothesis.

  17. KRAS, HRAS and EGFR Mutations in Sporadic Sebaceous Gland Hyperplasia.

    PubMed

    Groesser, Leopold; Singer, Sebastian; Peterhof, Eva; Landthaler, Michael; Heigl, Ulrike; Schneider-Brachert, Wulf; Berneburg, Mark; Hafner, Christian

    2016-08-23

    Sporadic sebaceous gland hyperplasia (SGH) is a benign skin lesion, with a high prevalence in the general population. Although SGH has been attributed to both extrinsic and intrinsic factors, the underlying genetic changes have not yet been characterized. Recently, HRAS and KRAS mutations have been identified in sebaceous naevus, a hamartoma sharing histological characteristics with SGH. Therefore we screened 43 SGH for activating mutations in RAS genes and other oncogenes. We identified a wide spectrum of mutually exclusive activating HRAS (8/43), KRAS (11/43) and EGFR mutations (7/31) in altogether 60% of the lesions investigated. A RAS and EGFR wildtype status was found in 15 normal sebaceous glands in the head and neck area. Our findings indicate that activating HRAS, KRAS and EGFR mutations play a major role in the pathogenesis of sporadic SGH. These results support the concept that SGH is a true benign neoplasm rather than a reactive hyperplasia. PMID:26804118

  18. Electron temperature measurements in mid-latitude sporadic E layers

    NASA Technical Reports Server (NTRS)

    Schutz, S. R.; Smith, L. G.

    1976-01-01

    By using rocket-borne Langmuir probes, electron temperature profiles have been obtained in five mid-latitude sporadic E layers. The data show the electron temperature within the layers to be lower than the electron temperature at the adjacent altitudes. This is consistent with the layers' being maintained by a vertical redistribution of ionization. The magnitude of the observed electron temperature variation is, however, larger than expected.

  19. 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.

  20. Paralytic illness resembling inflammatory polyradiculoneuropathy in a chimpanzee.

    PubMed

    Alford, P L; Satterfield, W C

    1995-07-01

    An adult male chimpanzee housed in an outdoor corral with a group of other chimpanzees had an acute onset of ascending motor paresis that progressed to flaccid tetraplegia over 3 days. Tendon reflexes were weak, and CSF protein concentration was high. The chimpanzee regained normal mobility over several months. This chimpanzee's ascending, symmetrical, monophasic, flaccid paralytic illness, with albuminocytologic dissociation in CSF, and recovery following supportive treatment, was characteristic of inflammatory polyradiculoneuropathy, known as Guillain-Barré syndrome in human beings. Coonhound paralysis and experimentally induced allergic neuritis are the counterparts in dogs and laboratory animals, respectively, of the syndrome. In human beings, the syndrome is apparently immunologically mediated, as it is known to develop after bacterial and viral infections, vaccinations, and surgery or injury. The chimpanzee of this report had been given a rabies vaccination and had been treated for dental abscess 12 days prior to onset of signs, and had been inoculated with material containing neuronal antigens 20 years prior to onset of signs. PMID:7601702

  1. Pyknoachondrogenesis: an association of skeletal defects resembling achondrogenesis with generalized bone sclerosis. A new condition?

    PubMed

    Camera, G; Giordano, F; Mastroiacovo, P

    1986-10-01

    A stillborn male with skeletal anomalies resembling achondrogenesis with remarkably sclerotic bones is reported. The term "Pyknoachondrogenesis" is suggested for this hitherto undescribed condition. PMID:3791681

  2. Sporadic hemangioblastomas are characterized by cryptic VHL inactivation.

    PubMed

    Shankar, Ganesh M; Taylor-Weiner, Amaro; Lelic, Nina; Jones, Robert T; Kim, James C; Francis, Joshua M; Abedalthagafi, Malak; Borges, Lawrence F; Coumans, Jean-Valery; Curry, William T; Nahed, Brian V; Shin, John H; Paek, Sun Ha; Park, Sung-Hye; Stewart, Chip; Lawrence, Michael S; Cibulskis, Kristian; Thorner, Aaron R; Van Hummelen, Paul; Stemmer-Rachamimov, Anat O; Batchelor, Tracy T; Carter, Scott L; Hoang, Mai P; Santagata, Sandro; Louis, David N; Barker, Fred G; Meyerson, Matthew; Getz, Gad; Brastianos, Priscilla K; Cahill, Daniel P

    2014-01-01

    Hemangioblastomas consist of 10-20% neoplastic "stromal" cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas. PMID:25589003

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

    PubMed

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

    2016-05-01

    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

  4. Effects of sulindac on sporadic colorectal adenomatous polyps.

    PubMed Central

    Matsuhashi, N; Nakajima, A; Fukushima, Y; Yazaki, Y; Oka, T

    1997-01-01

    BACKGROUND: Although sulindac is known to cause regression of colorectal adenomatous polyps in familial adenomatous polyposis, less is known about the effect of sulindac on sporadic adenomas. The precise mechanisms of these effects also remain to be determined. AIMS: Sulindac was given to patients with sporadic colorectal adenomatous polyps to evaluate its effects on them, and histological analysis was performed to elucidate the mechanism of the polyp regression, as well the kind of adenomatous polys that are susceptible to the agent. SUBJECTS: 20 adenomatous polyps in 15 patients were studied. METHODS: Sulindac (300 mg daily) was given for four months, followed by colonoscopy with removal of the residual polyps. Polyp size, degree of atypia, inflammatory cell infiltration in the polyps, and immunostaining for mutant p53 product were evaluated before and after treatment. RESULTS: 13 of the 20 polyps shrank or disappeared. Patient sex, polyp location, size, degree of atypia, or p53 mutation did not affect the response, but polyps in older patients were more sensitive to sulindac. The degree of atypia or inflammatory cell infiltration was not affected by the treatment. A polyp containing a focal cancer was unresponsive. CONCLUSIONS: Sulindac can cause regression of sporadic colorectal adenomatous polyps. Images PMID:9135523

  5. 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.

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

    PubMed

    Davis, C J; Johnson, C G

    2005-06-01

    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. PMID:15944700

  7. CHCHD2 gene mutations in familial and sporadic Parkinson's disease.

    PubMed

    Shi, Chang-He; Mao, Cheng-Yuan; Zhang, Shu-Yu; Yang, Jing; Song, Bo; Wu, Ping; Zuo, Chuan-Tao; Liu, Yu-Tao; Ji, Yan; Yang, Zhi-Hua; Wu, Jun; Zhuang, Zheng-Ping; Xu, Yu-Ming

    2016-02-01

    Mutations in CHCHD2 gene have been reported in autosomal dominant Parkinson's disease (ADPD). However, there is still lack of evidence supported CHCHD2 mutations lead to ADPD in other populations. We performed whole exome sequencing, positron emission tomography (PET), and haplotype analyses in an ADPD pedigree and then comprehensively screened for CHCHD2 gene mutations in additional 18 familial parkinsonism pedigrees, 364 sporadic PD patients, and 384 healthy controls to assess the frequencies of known and novel rare nonsynonymous CHCHD2 mutations. We identified a heterozygous variant (c.182C>T; p.Thr61Ile) in the CHCHD2 gene in the ADPD pedigree. PET revealed a significant reduction in dopamine transporter binding in the putamen and caudate nucleus of the proband, similar to idiopathic PD. The single nucleotide variant 5C>T (Pro2Leu) in CHCHD2 was confirmed to have a significantly higher frequency among sporadic PD patients than controls. Our results confirm that ADPD can be caused by CHCHD2 mutations and show that the Pro2Leu variant in CHCHD2 may be a risk factor for sporadic PD in Chinese populations. PMID:26705026

  8. Clinical significance of midkine expression in sporadic desmoid tumors

    PubMed Central

    KIM, HEE SUNG; KIM, JIN; NAM, KYUNG HAN; KIM, WOO HO

    2016-01-01

    The aim of the present study was to identify the prognostic factors for the propensity for recurrence in sporadic desmoid tumors. The catenin (cadherin-associated protein) β1 (CTNNB1) genotypes and expression of Wnt pathway proteins and midkine (also termed neurite growth-promoting factor 2) were investigated in 159 patients with sporadic desmoid tumors. Formalin-fixed paraffin-embedded tissues of the surgically resected desmoid tumors were examined by direct sequencing of CTNNB1 exon 3, and immunostained for the expression of β-catenin, T-cell factor 4 (TCF-4), phosphorylated protein kinase B (pAkt), midkine and menin using a tissue microarray method. Among the samples, 70% (111/159) exhibited point mutations of the CTNNB1 gene, including T41A (56%), S45F (8%), S45P (2%), S45N (2%) and T42A (1%). In addition, 100, 57, 24, 15 and 92% of the tumors expressed β-catenin, TCF-4, midkine, pAkt and menin, respectively. Positive midkine expression was significantly associated with the recurrence of tumors (P=0.001). The multivariate analysis of recurrence demonstrated that an extra-abdominal tumor site [hazard ratio (HR), 2.625; P=0.001] and midkine expression (HR, 2.077; P<0.009) were independent prognostic factors of tumor recurrence. In conclusion, the present results suggest that the tumor site and midkine expression may be predictive markers for the recurrence of sporadic desmoid tumors. PMID:26998061

  9. Histopathologic, immunohistochemical, and polymerase chain reaction assays in the study of cases with fatal sporadic myocarditis.

    PubMed

    Guarner, Jeannette; Bhatnagar, Julu; Shieh, Wun-Ju; Nolte, Kurt B; Klein, Dennis; Gookin, Michelle S; Peñaranda, Silvia; Oberste, M Steven; Jones, Tara; Smith, Chalanda; Pallansch, Mark A; Zaki, Sherif R

    2007-09-01

    Paraffin tissue blocks from 27 cases with sporadic myocarditis were collected during a 12-year period at a single medical examiner's office. Blocks were studied by using histopathology; immunohistochemistry for viruses (adenovirus, enterovirus, influenza A and B, and human herpes types 4 and 5), bacteria (Neisseria meningitidis, Ehrlichia sp, spotted fever group Rickettsia) and parasites (Toxoplasma gondii and Trypanosoma cruzi); and polymerase chain reaction (PCR)/RT-PCR for adenovirus and enterovirus. We identified enterovirus in 5 (18.5%) cases and Sarcocystis in a 36-year-old woman who had focal inflammation and myocyte necrosis. Immunohistochemical evidence of enteroviruses was found in the myocytes of 2 patients less than 6 months old who had diffuse mononuclear myocardial inflammation, interstitial pneumonitis; one also had encephalitis. In these 2 patients, the presence of enterovirus was confirmed by RT-PCR targeting the 5' nontranslated region and was serotyped as coxsackievirus B2 by sequencing the VP1 capsid region. In another 3 cases (ages 12, 47, and 54), enterovirus was detected by the 5' nontranslated region region; VP1 sequencing identified these as echoviruses 6, 13, and 7, respectively. Accurately identifying an infectious agent is the foundation for clinical and public health interventions. Despite using multiple diagnostic methods, an organism could only be detected in a small proportion of sporadic myocarditis cases. PMID:17602724

  10. Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma.

    PubMed

    Zhou, Yunli; Zhang, Xun; Klibanski, Anne

    2014-04-01

    Human pituitary adenomas are the most common intracranial neoplasms. Approximately 5% of them are familial adenomas. Patients with familial tumors carry germline mutations in predisposition genes, including AIP, MEN1 and PRKAR1A. These mutations are extremely rare in sporadic pituitary adenomas, which therefore are caused by different mechanisms. Multiple tumor suppressive genes linked to sporadic tumors have been identified. Their inactivation is caused by epigenetic mechanisms, mainly promoter hypermethylation, and can be placed into two groups based on their functional interaction with tumor suppressors RB or p53. The RB group includes CDKN2A, CDKN2B, CDKN2C, RB1, BMP4, CDH1, CDH13, GADD45B and GADD45G; AIP and MEN1 genes also belong to this group. The p53 group includes MEG3, MGMT, PLAGL1, RASSF1, RASSF3 and SOCS1. We propose that the tumor suppression function of these genes is mainly mediated by the RB and p53 pathways. We also discuss possible tumor suppression mechanisms for individual genes. PMID:24035864

  11. Loss of heterozygosity at the BRCA1 locus in Tunisian women with sporadic breast cancer.

    PubMed

    Charef-Hamza, Sameh; Trimeche, Mounir; Ziadi, Sonia; Amara, Khaled; Gaddas, Naim; Mokni, Moncef; Sriha, Badreddine; Yacoubi, Tahar; Korbi, Sadok

    2005-06-28

    Breast cancer in Tunisia is characterized by a much higher incidence of aggressiveness compared with Western countries. The pattern of allelic loss at the BRCA1 locus in Tunisian women with breast carcinoma has not been studied. Therefore, the aim of this present preliminary study was mainly focused on loss of heterozygosity (LOH) analysis of the BRCA1 gene to determine if this tumor suppressor gene is involved in sporadic breast carcinoma among Tunisian women. We investigate allelic losses by analyzing three microsatellite markers in the BRCA1 region, in a panel of 21 human breast tumors. D17S1322 marker had the highest frequency of LOH (59%), followed by the D17S1323 (35%), and EDH-17B (20%). Collectively out of 21 informative cases 13 (62%) showed LOH at at least one BRCA1 locus. This data provides evidence that allelic loss at BRCA1 is a frequent event in sporadic breast tumorigenesis among Tunisian women, and suggests that the BRCA1 gene might play an important role as a tumor suppressor gene. PMID:15914269

  12. Growth and Invasion of Sporadic Colorectal Adenocarcinomas in Terms of Genetic Change

    PubMed Central

    Roh, Seon Ae; Choi, Eun Young; Cho, Dong Hyung; Jang, Se Jin; Kim, Seon Young; Kim, Yong Sung

    2010-01-01

    Integrative genetic changes were examined in relation to tumor growth and progression of sporadic colorectal cancers. Ninety-two sporadic colorectal cancer patients and 12 human colorectal cancer cell lines were evaluated. Genetic changes in representative steps of colorectal tumorigenesis were determined. Biological characteristics, i.e., clinicopathologic parameters, expression of invasion-associated molecules, and in vitro invasion and migration, in association with these changes were further analyzed. Adenomatous polyposis coli (APC) and/or Wnt-activated alterations occurred in 66% patients, whereas mismatch repair (MMR) defects and/or RAF-mediated alterations were identified in 47% patients. The crossover rate between these two alterations was 26%. Differential mRNA expression of ARK5 was closely associated with that of MMP2, MMP9, and S100A4 (P≤0.044-0.001). Additionally, enhanced ARK5 mRNA expression was more frequent in tumors displaying RAF-mediated alterations and crossover pathways (P=0.01 and 0.03, respectively). Upregulation of CEA mRNA was more common in the advanced stages (P=0.034), while VEGF expression was greater in poorly differentiated or mucinous tumors (P=0.042). The high expressions of MMP2 and MMP9 were closely associated with invasion and migration of colorectal tumors and cell lines. Our results conclusively show that specific pathways of colorectal tumorigenesis are closely associated with characteristic tumor growth and invasion. PMID:20191032

  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. Progranulin null mutations in both sporadic and familial frontotemporal dementia.

    PubMed

    Le Ber, Isabelle; van der Zee, Julie; Hannequin, Didier; Gijselinck, Ilse; Campion, Dominique; Puel, Michèle; Laquerrière, Annie; De Pooter, Tim; Camuzat, Agnès; Van den Broeck, Marleen; Dubois, Bruno; Sellal, François; Lacomblez, Lucette; Vercelletto, Martine; Thomas-Antérion, Catherine; Michel, Bernard-François; Golfier, Véronique; Didic, Mira; Salachas, François; Duyckaerts, Charles; Cruts, Marc; Verpillat, Patrice; Van Broeckhoven, Christine; Brice, Alexis

    2007-09-01

    Frontotemporal dementia (FTD) is the second most frequent type of neurodegenerative dementias. Mutations in the progranulin gene (GRN, PGRN) were recently identified in FTDU-17, an FTD subtype characterized by ubiquitin-immunoreactive inclusions and linkage to chromosome 17q21. We looked for PGRN mutations in a large series of 210 FTD patients (52 familial, 158 sporadic) to accurately evaluate the frequency of PGRN mutations in both sporadic and familial FTD, and FTD with associated motoneuron disease (FTD-MND), as well as to study the clinical phenotype of patients with a PGRN mutation. We identified nine novel PGRN null mutations in 10 index patients. The relative frequency of PGRN null mutations in FTD was 4.8% (10/210) and 12.8% (5/39) in pure familial forms. Interestingly, 5/158 (3.2%) apparently sporadic FTD patients carried a PGRN mutation, suggesting the possibility of de novo mutations or incomplete penetrance. In contrast, none of the 43 patients with FTD-MND had PGRN mutations, supporting that FTDU-17 and FTD-MND are genetically distinct. The clinical phenotype of PGRN mutation carriers was particular because of the wide range in onset age and the frequent occurrence of early apraxia (50%), visual hallucinations (30%), and parkinsonism (30%) during the course of the disease. This study supports that PGRN null mutations represent a more frequent cause of FTD than MAPT mutations (4.8% vs. 2.9%) but are not responsible for FTD-MND. It also demonstrates that half of the patients with a PGRN mutation in our series had no apparent family history of dementia. Taking this into account, genetic testing should be now considered more systematically, even in patients without obvious familial history of FTD. PMID:17436289

  15. Microsatellite instability and the clinicopathological features of sporadic colorectal cancer

    PubMed Central

    Ward, R; Meagher, A; Tomlinson, I; O'Connor, T; Norrie, M; Wu, R; Hawkins, N

    2001-01-01

    BACKGROUND AND AIMS—In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice.
METHODS—DNA was extracted from 310 tumours collected from 302 consecutive individuals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53.
RESULTS—Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%.
CONCLUSIONS—We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.


Keywords: colorectal carcinoma; microsatellite instability; survival; MLH1; MSH2; immunohistochemistry PMID:11358903

  16. 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).

  17. [Pathogenesis and clinical manifestations of sporadic cerebral small vessel disease].

    PubMed

    Staszewski, Jacek; Piusińska-Macoch, Renata; Skrobowska, Ewa; Pawlik, Rafał; Brodacki, Bogdan; Stępień, Adam

    2015-12-01

    Sporadic small vessel disease (sSVD) is one of the most common vascular disease of the central nervous system (CNS). It is the main cause of lacunar stokes, hemorrhages to deep brain regions and chronic CNS diseases such as vascular parkinsonism and dementia. Beside a high and growing incidence of sSVD especially in the elderly population, the knowledge of ethiopathogenesis and optimal treatment of sSVD have not been established. The article summarizes different clinical manifestations (acute and chronic) as well as heterogenous radiologic changes found in CNS neuroimaging. PMID:26802696

  18. Emerging therapeutic options for sporadic inclusion body myositis

    PubMed Central

    Alfano, Lindsay N; Lowes, Linda P

    2015-01-01

    Sporadic inclusion body myositis is the most common inflammatory muscle disorder preferentially affecting males over the age of 40 years. Progressive muscle weakness of the finger flexors and quadriceps muscles results in loss of independence with activities of daily living and eventual wheelchair dependence. Initial signs of disease are often overlooked and can lead to mis- or delayed diagnosis. The underlying cause of disease is unknown, and disease progression appears refractory to available treatment options. This review discusses the clinical presentation of inclusion body myositis and the current efforts in diagnosis, and focuses on the current state of research for both nonpharmacological and pharmacological treatment options for this patient group. PMID:26445546

  19. Sporadic Cerebral Amyloid Angiopathy: Pathophysiology, Neuroimaging Features, and Clinical Implications.

    PubMed

    Boulouis, Gregoire; Charidimou, Andreas; Greenberg, Steven M

    2016-06-01

    Sporadic cerebral amyloid angiopathy is a small vessel disorder defined pathologically by progressive amyloid deposition in the walls of cortical and leptomeningeal vessels resulting from disruption of a complex balance between production, circulation, and clearance of amyloid-β peptide (Aβ) in the brain. Cerebral amyloid angiopathy is a major cause of lobar symptomatic intracerebral hemorrhage, transient focal neurologic episodes, and a key contributor to vascular cognitive impairment. The mechanisms and consequences of amyloid-β deposition at the pathological level and its neuroimaging manifestations, clinical consequences, and implications for patient care are addressed in this review. PMID:27214698

  20. Atypical prion diseases in humans and animals.

    PubMed

    Tranulis, Michael A; Benestad, Sylvie L; Baron, Thierry; Kretzschmar, Hans

    2011-01-01

    Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrP(Sc)), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans. PMID:21598097

  1. 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

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

    PubMed

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

    2016-07-01

    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

  3. Genetic defects associated with familial and sporadic hyperparathyroidism.

    PubMed

    Hendy, Geoffrey N; Cole, David E C

    2013-01-01

    Primary hyperparathyroidism (PHPT) occurs sporadically, but occasionally it may be a feature of a familial condition, such as multiple endocrine neoplasia type 1 (MEN1), MEN2A, or the HPT-jaw tumor syndrome (HPT-JT), and familial hypocalciuric hypercalcemia/neonatal severe hyperparathyroidism (FHH/NSHPT). PHPT may also occur as familial isolated hyperparathyroidism (FIHP), and has been observed as a consequence of mutations in the CDKN1B gene (MEN4). Tumorigenesis in these conditions may be the result of protooncogene activation (e.g. RET in MEN2) or two-hit losses of a tumor suppressor (e.g. MEN1, HPT-JT). In patients with MEN1, HPT-JT or FHH/NSHPT, the hyperparathyroidism manifests at a younger age and affects both sexes equally. In MEN1, mutations of the MEN1 gene also cause enteropancreatic and anterior pituitary tumors. In MEN2, activating mutations in the RET protooncogene also cause medullary thyroid carcinoma and pheochromocytoma. In HPT-JT, mutations of CDC73/HRPT2 are associated with parathyroid carcinoma, but tumors of the kidneys and uterus are additional features. In some FIHP families, a CASR mutation may be identified. In parathyroid carcinoma, even if sporadic, molecular diagnostics for CDC73/HRPT2 should be considered, as it should be for younger patients. Further exploration of these hereditary syndromes may shed light on the molecular mechanisms giving rise to nonhereditary PHPT. PMID:23652676

  4. Sporadic-E layers and unstable wind shears

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

    Electron density profiles of sporadic-E layers have been observed with good height resolution using rocket-borne probes. These generally show a simple shape consistent with the effect of a linear wind shear acting on metallic ions. Occasionally more complex shapes have been recorded, including double peaks and, on one occasion, a nearly rectangular profile. A direct method of obtaining the wind profile from the concentration profile of metallic ions has been developed. The metallic ion concentration profile itself is obtained from the electron density profile. Both procedures derive from the steady-state continuity equation. For linear wind shears it is found that the maximum value of the shear is about 50 m/s/km which corresponds to a Richardson number of 1/4. Layers of complex shape are associated with non-linear wind shears in which the maximum shear considerably exceeds this value. It is concluded that the complex profiles of sporadic-E layers can be interpreted as an effect of unstable wind shears.

  5. 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. PMID:25931254

  6. 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

  7. 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

  8. 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. PMID:19372010

  9. Effects of parenting quality on adolescents' personality resemblance to their parents. The TRAILS study.

    PubMed

    Langenhof, M Rohaa; Komdeur, Jan; Oldehinkel, Albertine J

    2016-08-01

    This study considers the development of resemblance between 741 adolescents and their biological parents, across six NEO-PI-R personality traits known to be important in psychological problems: anger-hostility, impulsiveness, vulnerability, assertiveness, excitement-seeking, and self-discipline. We modelled the association between perceived parental warmth and rejection at age eleven and personality resemblance to parents at about age sixteen. Parenting experienced during early adolescence was related to the degree and direction in which adolescents resembled their parents five years later in life. Rejection, especially from fathers, significantly predicted a smaller resemblance to both the parents. Girls were more strongly affected by parental quality than boys, and there was some indication that adolescents responded in opposite ways to parenting from mothers and fathers. This study is a first step in uncovering the complex interplay between parenting, gender, and the current generation's ability to develop personality traits independent from the previous generation. PMID:27400032

  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. 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.

  12. Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer

    PubMed Central

    Gonzalo, Victoria; Lozano, Juan José; Muñoz, Jenifer; Balaguer, Francesc; Pellisé, Maria; de Miguel, Cristina Rodríguez; Andreu, Montserrat; Jover, Rodrigo; Llor, Xavier; Giráldez, M. Dolores; Ocaña, Teresa; Serradesanferm, Anna; Alonso-Espinaco, Virginia; Jimeno, Mireya; Cuatrecasas, Miriam; Sendino, Oriol; Castellví-Bel, Sergi; Castells, Antoni

    2010-01-01

    Background Colorectal cancer (CRC) multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. Methodology/Principal Findings We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals) and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2), RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008) and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047) as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006). Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17), SFRP1 (r = 0.83, 0.06), HPP1 (r = 0.64, p = 0.17), 3OST2 (r = 0.83, p = 0.06) and GATA4 (r = 0.6, p = 0.24). Methylation in normal appearing colorectal mucosa from patients with multiple

  13. Feline perforating dermatitis resembling human reactive perforating collagenosis: clinicopathological findings and outcome in four cases.

    PubMed

    Albanese, Francesco; Tieghi, Chiara; De Rosa, Luigi; Colombo, Silvia; Abramo, Francesca

    2009-08-01

    The clinicopathological findings of perforating dermatitis in two young and two adult cats are described. In all cases, the lesions were characterized by single or multiple papules and plaques, 0.5-3.0 cm in diameter, each containing a central, firm, exophytic, cone-shaped, yellow-orange keratotic plug, tightly adherent to the underlying skin. Removal of the protruding material was associated with bleeding and left the ulcerated surface exposed. In one case, the lesions showed a linear configuration and identical lesions occurred on the suture sites following biopsy. Histopathologically, the diagnosis was straightforward because of the presence of vertically orientated collagen bundles extruded from ulcerated, concave-shaped invaginations of the skin. In two cases, vitamin C administration failed to resolve the disease. In two cases, methyl-prednisolone acetate was used to manage relapsing episodes and vitamin C helped to reduce glucocorticoid requirements. In one case, treatment with methyl-prednisolone acetate only appeared to be curative. The fourth case was lost to follow-up immediately after the diagnosis. PMID:19659539

  14. Integer-Valued Characters for Some Sporadic Groups

    NASA Astrophysics Data System (ADS)

    Gilani, Alireza; Moghani, Ali

    2010-11-01

    Using the concept of markaracter tables proposed by a Chemist S. Fujita who applied his results in this area of research to enumerate isomers of molecules, we are able to discuss characters and marks concerning a group of a finite order on a common basis. He also introduced tables of integer-valued characters that are obtained for finite groups. According to the main result of W. Feit and G. M. Seitz (see, Illinois J. Math. 33 (1), 103-131, 1988), the sporadic Mathieu groups M11, M12 and Higman-Sims (HS) group are unmatured. In this paper, at first all the dominant classes and Q- conjugacy characters for the above groups are derived.

  15. An unusual case of sporadic Creutzfeldt-Jakob disease (CJD).

    PubMed

    Javed, Qaiser; Alam, Faouzi; Krishna, Sowmya; Jaganathan, Geetha

    2010-01-01

    A 49-year-old healthy white British female, not previously known to psychiatric services, presented with an acute onset of florid psychotic symptoms. Her symptoms included visual, auditory and tactile hallucinations as well as persecutory delusions. She was started on antipsychotic medication; however, her psychotic symptoms did not improve significantly in the first 3 months. Her blood tests were normal. Lumbar puncture was performed which was positive for protein 14-3-3. A computed tomography scan of the brain showed generalised atrophic changes. The history of early visual hallucinations, rapid cognitive decline and positive 14-3-3 result was in keeping with the Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD). Despite a short life expectancy as reported in literature, our patient, who was diagnosed with sCJD more than two-and-a-half years ago, is still alive. We therefore believe this is an important finding to report. PMID:22753302

  16. [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. PMID:15619815

  17. [Sporadic Cerebral Amyloid Angiopathy: An Overview with Clinical Cases].

    PubMed

    Schöberl, F; Eren, O E; Wollenweber, F A; Kraus, T; Kellert, L

    2016-09-01

    Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease in the elderly. Neuropathologically, it is characterized by deposition of amyloid-ß (Aß) in the wall of small to medium-sized arteries, capillaries and venules of the cerebral cortex and leptomeninges. Over the last years it was recognized as an important cause of spontaneous intracerebral hemorrhage and cognitive deficits in the elderly. The clinical and radiological manifestations are diverse ranging from acute onset focal neurological deficits due to intracerebral lobar hemorrhage to subacute progressive cognitive impairment due to Aß-mediated inflammation confluent subcortical edema. The wide clinico-radiological spectrum of CAA is a major challenge for the neurologist and stroke physician. This review provides a structured and detailed look at recent developments in CAA, and is illustrated with case studies. PMID:27607067

  18. 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.

  19. Distinct X-chromosome SNVs from some sporadic AD samples

    PubMed Central

    Gómez-Ramos, A.; Podlesniy, P.; Soriano, E.; Avila, J.

    2015-01-01

    Sporadic Alzheimer disease (SAD) is the most prevalent neurodegenerative disorder. With the development of new generation DNA sequencing technologies, additional genetic risk factors have been described. Here we used various methods to process DNA sequencing data in order to gain further insight into this important disease. We have sequenced the exomes of brain samples from SAD patients and non-demented controls. Using either method, we found a higher number of single nucleotide variants (SNVs), from SAD patients, in genes present at the X chromosome. Using the most stringent method, we validated these variants by Sanger sequencing. Two of these gene variants, were found in loci related to the ubiquitin pathway (UBE2NL and ATXN3L), previously do not described as genetic risk factors for SAD. PMID:26648445

  20. Sporadic inclusion body myositis: the genetic contributions to the pathogenesis

    PubMed Central

    2014-01-01

    Sporadic inclusion body myositis (sIBM) is the commonest idiopathic inflammatory muscle disease in people over 50 years old. It is characterized by slowly progressive muscle weakness and atrophy, with typical pathological changes of inflammation, degeneration and mitochondrial abnormality in affected muscle fibres. The cause(s) of sIBM are still unknown, but are considered complex, with the contribution of multiple factors such as environmental triggers, ageing and genetic susceptibility. This review summarizes the current understanding of the genetic contributions to sIBM and provides some insights for future research in this mysterious disease with the advantage of the rapid development of advanced genetic technology. An international sIBM genetic study is ongoing and whole-exome sequencing will be applied in a large cohort of sIBM patients with the aim of unravelling important genetic risk factors for sIBM. PMID:24948216

  1. [Sporadic Late-Onset Nemaline Myopathy Associated with MGUS].

    PubMed

    Nagai, Taiji; Sunada, Yoshihide

    2015-12-01

    Sporadic late-onset nemaline myopathy is an uncommon disease. Clinically, it is characterized by progressive muscle weakness that can develop in limbs or axial muscles. Asymmetrical distal weakness, facial weakness, dropped head, and dysphagia can also occur. Since the serum creatine kinase level usually remains within the normal range, patients can be misdiagnosed with motor neuron disease. Recognition of nemaline rods on muscle biopsy is crucial for accurate diagnosis. If it is associated with monoclonal gammopathy of undetermined significance, the outcome is known to be unfavorable. In spite of various immunotherapies such as corticosteroids, immunosuppressants, and plasmapheresis, most patients die of respiratory failure within 5 years. Since the efficacy of autologous stem cell transplantation following high-dose melphalan was first reported in 2008, there have been accumulating reports that showed the positive effect of this therapy for the disease. PMID:26618766

  2. Cognitive Impairment in Chinese Patients with Sporadic Amyotrophic Lateral Sclerosis

    PubMed Central

    Cui, Bo; Cui, Liying; Gao, Jing; Liu, Mingsheng; Li, Xiaoguang; Liu, Caiyan; Ma, Junfang; Fang, Jia

    2015-01-01

    Background It has reached a consensus that patients with amyotrophic lateral sclerosis (ALS) could display cognitive impairment characterized by executive dysfunction or even dementia, but cognitive spectrum of Chinese patients with ALS still waits to be documented. Methods A total of 106 incident patients with sporadic ALS were enrolled and comprehensive neuropsychological tests covering memory, executive function, attention, language, and visuospatial function were administered to them. Neuropsychological performances of 76 age- and education- matched healthy controls were used for the purpose of classification and comparison. Results 106 patients were categorized into 4 subtypes:84 (79.2%) ALS with normal cognition (ALS-NC), 12 (11.3%) ALS with executive cognitive impairment (ALS-ECI), 5 (4.7%) ALS with non-executive cognitive impairment (ALS-NECI), and 5 (4.7%) ALS with frontotemporal lobe degeneration (ALS-FTLD). Under the same criteria, 2 (2.6%) and 1 (1.3%) healthy controls were diagnosed as ECI and NECI, respectively. The proportion of ECI was significantly higher in non-demented ALS than that in healthy controls, but it was not for NECI. Patients with ALS-FTLD had significantly severer bulbar function and older age than those with ALS-NC. Conclusion Comorbid FTLD occurred in around 5% of Chinese sporadic ALS cases. Different genetic background and unique age distribution of Chinese ALS patients might be the reasons for the relatively low rate of comorbid FTLD. Cognitive dysfunction, predominant but not exclusive in executive area, was present in around 16% of non-demented ALS patients. PMID:26367133

  3. 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. PMID:26752512

  4. Inferior cerebellar hypoplasia resembling a Dandy-Walker-like malformation in purebred Eurasier dogs with familial non-progressive ataxia: a retrospective and prospective clinical cohort study.

    PubMed

    Bernardino, Filipa; Rentmeister, Kai; Schmidt, Martin J; Bruehschwein, Andreas; Matiasek, Kaspar; Matiasek, Lara A; Lauda, Alexander; Schoon, Heinz A; Fischer, Andrea

    2015-01-01

    Cerebellar malformations can be inherited or caused by insults during cerebellar development. To date, only sporadic cases of cerebellar malformations have been reported in dogs, and the genetic background has remained obscure. Therefore, this study`s objective was to describe the clinical characteristics, imaging features and pedigree data of a familial cerebellar hypoplasia in purebred Eurasier dogs. A uniform cerebellar malformation characterized by consistent absence of the caudal portions of the cerebellar vermis and, to a lesser degree, the caudal portions of the cerebellar hemispheres in association with large retrocerebellar fluid accumulations was recognized in 14 closely related Eurasier dogs. Hydrocephalus was an additional feature in some dogs. All dogs displayed non-progressive ataxia, which had already been noted when the dogs were 5-6 weeks old. The severity of the ataxia varied between dogs, from mild truncal sway, subtle dysmetric gait, dysequilibrium and pelvic limb ataxia to severe cerebellar ataxia in puppies and episodic falling or rolling. Follow-up examinations in adult dogs showed improvement of the cerebellar ataxia and a still absent menace response. Epileptic seizures occurred in some dogs. The association of partial vermis agenesis with an enlarged fourth ventricle and an enlarged caudal (posterior) fossa resembled a Dandy-Walker-like malformation in some dogs. Pedigree analyses were consistent with autosomal recessive inheritance. PMID:25668516

  5. 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.

  6. A novel TUBB3 mutation in a sporadic patient with asymmetric cortical dysplasia.

    PubMed

    Shimojima, Keiko; Okamoto, Nobuhiko; Yamamoto, Toshiyuki

    2016-04-01

    Recent advances in molecular technology have led to the discovery of several genes related to human malformations of cortical development (MCDs). The beta-tubulin class III gene (TUBB3) was identified as a gene responsible for MCDs. Although mouse-model experiments have not revealed any findings of neuronal migration disorders, human TUBB3 mutations have been identified in patients with congenital fibrosis of the extraocular muscles. Since the discovery of a TUBB3 mutation, only 15 mutations have been identified. In this study, comprehensive mutation screening through next-generation sequencing identified a novel TUBB3 mutation (p.Ser230Leu) in a sporadic patient with moderate developmental delay associated with mild MCD. Compared to patients with the alpha-tubulin class 1a gene (TUBA1A) mutations, patients with TUBB3 mutations show milder phenotypic manifestations and milder MCD. Therefore, patients with milder MCD manifestations may be under-diagnosed, and TUBB3 mutations may be rarely identified. Additional genotype-phenotype information should be accumulated for further understanding of the TUBB3 functional relevance. © 2016 Wiley Periodicals, Inc. PMID:26739025

  7. 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.

  8. 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

  9. Novel genetic mutations in a sporadic port-wine stain.

    PubMed

    Lian, Christine Guo; Sholl, Lynette M; Zakka, Labib R; O, Teresa M; Liu, Cynthia; Xu, Shuyun; Stanek, Ewelina; Garcia, Elizabeth; Jia, Yonghui; MacConaill, Laura E; Murphy, George F; Waner, Milton; Mihm, Martin C

    2014-12-01

    IMPORTANCE Port-wine stains (PWSs) are common congenital cutaneous capillary malformations. A somatic GNAQ mutation was recently identified in patients with sporadic PWSs and Sturge-Weber syndrome. However, subsequent studies to confirm or extend this observation are lacking.OBSERVATIONS We report a long-standing, unilateral facial PWS of a man in his early 70s confirmed by histopathological analysis. Staged surgical excision of the vascular malformation was performed, and genomic DNA was extracted from the vascular malformation specimen and normal skin. Targeted next-generation sequencing of the coding sequence of 275 known cancer genes including GNAQ was performed in both specimens. A single-nucleotide variant(c.548G>A, p.Arg183Gln) in GNAQ was identified in the PWS-affected tissue but not in the normal skin sample. In addition, this sequencing approach uncovered several additional novel somatic mutations in the genes SMARCA4, EPHA3, MYB, PDGFR-β, and PIK3CA.CONCLUSIONS AND RELEVANCE Our findings confirm the presence of somatic mutations inGNAQ in the affected skin of a patient with congenital PWS, as well as alterations in several other novel genes of possible importance in the pathogenesis of PWS that may also offer substantial therapeutic targets. PMID:25188413

  10. De novo variants in sporadic cases of childhood onset schizophrenia.

    PubMed

    Ambalavanan, Amirthagowri; Girard, Simon L; Ahn, Kwangmi; Zhou, Sirui; Dionne-Laporte, Alexandre; Spiegelman, Dan; Bourassa, Cynthia V; Gauthier, Julie; Hamdan, Fadi F; Xiong, Lan; Dion, Patrick A; Joober, Ridha; Rapoport, Judith; Rouleau, Guy A

    2016-06-01

    Childhood-onset schizophrenia (COS), defined by the onset of illness before age 13 years, is a rare severe neurodevelopmental disorder of unknown etiology. Recently, sequencing studies have identified rare, potentially causative de novo variants in sporadic cases of adult-onset schizophrenia and autism. In this study, we performed exome sequencing of 17 COS trios in order to test whether de novo variants could contribute to this disease. We identified 20 de novo variants in 17 COS probands, which is consistent with the de novo mutation rate reported in the adult form of the disease. Interestingly, the missense de novo variants in COS have a high likelihood for pathogenicity and were enriched for genes that are less tolerant to variants. Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, and thus may be considered as COS candidate genes. PMID:26508570

  11. 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.

  12. Nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas.

    PubMed Central

    Kovacs, G; Kung, H F

    1991-01-01

    For the development of renal cell carcinomas, it has been suggested that a germ-line or somatic mutation occurs on one of the homologous chromosomes 3p, and subsequently the other 3p segment is lost. We have examined the karyotype and/or the allelic combination on chromosomes 3 and 5 by restriction fragment length polymorphism analysis in normal kidney and tumor samples from 28 renal cell carcinomas that developed in two patients with von Hippel-Lindau disease; we then compared the results to those of sporadic tumors. An unbalanced translocation between chromosome 3p and 5q or other chromosomes was found to be the most common aberration. We developed a model of nonhomologous chromatid exchange involving breakpoint clusters at chromosomes 3p13, 3p11.2, 5q22, and 8q11.2. Subsequent chromatid segregation may result in net loss of the 3p segment either (i) in one step or (ii) after a nondisjunctional loss of the derivative chromosome carrying the 3p segment. This general mechanism could also be implicated to explain genetic changes occurring in other types of solid tumors. Images PMID:1986366

  13. Neurosecretases provide strategies to treat sporadic and familial Alzheimer disorders.

    PubMed

    Marks, Neville; Berg, Martin J

    2008-01-01

    Recent discoveries on neurosecretases and their trafficking to release fibril-forming neuropeptides or other products, are of interest to pathology, cell signaling and drug discovery. Nomenclature arose from the use of amyloid precursor protein (APP) as a prototypic type-1 substrate leading to the isolation of beta-secretase (BACE), multimeric complexes (gamma-secretase, gamma-SC) for intramembranal cleavage, and attributing a new function to well-characterized metalloproteases of the ADAM family (alpha-secretase) for normal APP turnover. While purified alpha/beta-secretases facilitate drug discovery, gamma-SC presents greater challenges for characterization and mechanisms of catalysis. The review comments on links between mutation or polymorphisms in relation to enzyme mechanisms and disease. The association between lipoprotein receptor LRP11 variants and sporadic Alzheimer's disease (SAD) offers scope to integrate components of pre- and post-Golgi membranes, or brain clathrin-coated vesicles within pathways for trafficking as targets for intervention. The presence of APP and metabolites in brain clathrin-coated vesicles as significant cargo with lipoproteins and adaptors focuses attention as targets for therapeutic intervention. This overview emphasizes the importance to develop new therapies targeting neurosecretases to treat a major neurological disorder that has vast economic and social implications. PMID:17719698

  14. 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.

  15. 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.

  16. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    PubMed Central

    Handra-Luca, Adriana; Dumuis-Gimenez, Marie-Laure; Bendib, Mouna; Anagnostis, Panagiotis

    2015-01-01

    Thyroid heterotopic bone formation (HBF) in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years). The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.). Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.). The number and size of HBFs (total: 28) ranged between 1 and 23/thyroid gland (one bilateral) and 1 and 10 mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular). The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp.) without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ≥2 mm), and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated. PMID:26697239

  17. Familial Resemblance for Measures of Reading Performance in Families of Reading-Disabled and Control Twins.

    ERIC Educational Resources Information Center

    Alarcon, Maricela; And Others

    1994-01-01

    Finds that parent-offspring resemblance in families of reading-disabled probands does not differ substantially from that in families of controls; and correlations and regressions for monozygotic twins are greater than those for dizygotic twins, suggesting that individual differences in reading achievement are due in part to heritable influences.…

  18. 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…

  19. Startle eye-blink modulation by facial self-resemblance and current mood.

    PubMed

    Finke, Johannes B; Larra, Mauro F; Schilling, Thomas M; Lass-Hennemann, Johanna; Blumenthal, Terry D; Schächinger, Hartmut

    2015-06-01

    Although salient stimuli are known to modulate startle eye-blink responses, and one's own face is considered of particular salience, effects of facial self-resemblance on startle responsiveness have not been systematically investigated. For the present study, pictures from the FACES database (rated as neutral) were digitally morphed to resemble the participants' (N=37) faces to varying degrees (25-50-75%). Perceptually matched geometrical shapes served as a control condition. At SOAs of either 300ms or 3000ms after picture onset, startle responses were elicited by white noise (50ms, 105dB), and recorded at the orbicularis oculi via EMG. Prior to the experiment, self-reported mood was assessed by means of the PANAS. Relative to non-face stimuli, the presentation of faces reduced startle magnitude at short, but not long, lead intervals. Furthermore, for probes presented at a SOA of 300ms, a linear decrease in startle magnitude with higher levels of self-resemblance was observed, presumably reflecting higher salience of the self-face. The startle modulating effect of self-resembling faces during longer lead intervals was moderated by the participants' current mood: negative affect predicted stronger patterns of attenuation, which might be interpreted as an increase in self-focus resulting from more negative mood. PMID:25913094

  20. An Analysis of the Claim that "Physical Education" Has Become a "Family Resemblance" Term.

    ERIC Educational Resources Information Center

    Zeigler, Earle F.

    In this paper, the author examines the confusion that currently exists concerning the term "physical education." In particular, he analyzes the claim that"physical education" is a "family resemblance" term--a word or phrase which may be used to denote fundamentally different concepts, but concepts in which there is some overlapping of…

  1. Immunohistochemical localization in rabbit brain of a peptide resembling the COOH-terminal octapeptide of cholecystokinin.

    PubMed Central

    Straus, E; Muller, J E; Choi, H S; Paronetto, F; Yalow, R S

    1977-01-01

    Immunohistochemical techniques were used to demonstrate the presence of a material resembling the COOH-terminal octapeptide of cholecystokinin in rabbit cerebral cortical neurons. Deep staining was seen in cell bodies throughout the cortical grey matter and diffusely in the subcortical white matter. Images PMID:331325

  2. 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. The meteors assigned to the various showers are identified in the CAMS Meteoroid Orbit Database 2.0 submitted to the IAU Meteor Data Center, and can be accessed also at

  3. Treatment of sporadic inclusion body myositis with bimagrumab

    PubMed Central

    Amato, Anthony A.; Sivakumar, Kumaraswamy; Goyal, Namita; David, William S.; Salajegheh, Mohammad; Praestgaard, Jens; Lach-Trifilieff, Estelle; Trendelenburg, Anne-Ulrike; Laurent, Didier; Glass, David J.; Roubenoff, Ronenn

    2014-01-01

    Objective: To study activin signaling and its blockade in sporadic inclusion body myositis (sIBM) through translational studies and a randomized controlled trial. Methods: We measured transforming growth factor β signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease (17 with sIBM). We tested inhibition of activin receptors IIA and IIB (ActRII) in 14 patients with sIBM using one dose of bimagrumab (n = 11) or placebo (n = 3). The primary outcome was the change in right thigh muscle volume by MRI at 8 weeks. Lean body mass, strength, and function were secondary outcomes. Twelve of the patients (10 bimagrumab, 2 placebo) participated in a subsequent 16-week observation phase. Results: Muscle SMAD2/3 phosphorylation was higher in sIBM than in other muscle diseases studied (p = 0.003). Eight weeks after dosing, the bimagrumab-treated patients increased thigh muscle volume (right leg +6.5% compared with placebo, p = 0.024; left leg +7.6%, p = 0.009) and lean body mass (+5.7% compared with placebo, p = 0.014). Subsequently, bimagrumab-treated patients had improved 6-minute walking distance, which peaked at 16 weeks (+14.6%, p = 0.008) compared with placebo. There were no serious adverse events; the main adverse events with bimagrumab were mild acne and transient involuntary muscle contractions. Conclusions: Transforming growth factor β superfamily signaling, at least through ActRII, is implicated in the pathophysiology of sIBM. Inhibition of ActRII increased muscle mass and function in this pilot trial, offering a potential novel treatment of sIBM. Classification of evidence: This study provides Class I evidence that for patients with inclusion body myositis, bimagrumab increases thigh muscle volume at 8 weeks. PMID:25381300

  4. 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

  5. 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. PMID:24643221

  6. 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

  7. 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

  8. Temperate zone sporadic-E maps /f/0/E/s/ greater than 7 MHz/

    NASA Technical Reports Server (NTRS)

    Smith, E. K.

    1978-01-01

    Three maps are presented of f(0) sporadic-E greater than 7 MHz for temperate zones. During map preparation it was assumed that: (1) the geographical area would be between plus and minus 60 deg geomagnetic latitude, excluding the equatorial zone, (2) the maps would be for f(0) sporadic-E greater than 7 MHz, (3) sunspot cycle variation would be ignored, (4) one map would represent the peak sporadic-E period with a discontinuity at the geographic equator, (5) one map would represent non-peak periods with a discontinuity at the geographic equator, (6) one map would represent all twelve months with no equatorial discontinuity, and (7) previously determined coefficients for median and upper decile f(0) sporadic-E would be extrapolated to 7 MHz.

  9. 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. PMID:26782687

  10. Determining the frequency of sporadic cases of rare X-linked disorders

    PubMed Central

    2016-01-01

    This paper gives formulae for calculating the gene frequency, incidence and proportion of sporadic cases of rare X-linked recessive disorders, taking account of the possibility of early recognition of carriers and fitness of affected males. PMID:27004222

  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. Horizontal structure of midlatitude sporadic-E layers observed by incoherent scatter radar

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

    The investigation reported is concerned with a model considered by Whitehead (1972). The partial transparency of the sporadic-E layer observed on certain occasions is attributed to regions of high electron density embedded in the layer. Observations obtained with an incoherent scatter radar facility are presented. Taking into account all factors, it is concluded that the partial transparency of sporadic-E layers, on the occasions of these observations, are explained by the Whitehead model.

  13. Seasonal correlation of sporadic schizophrenia to Ixodes ticks and Lyme borreliosis

    PubMed Central

    Fritzsche, Markus

    2002-01-01

    Background Being born in winter and spring is considered one of the most robust epidemiological risk factors for schizophrenia. The aetiology and exact timing of this birth excess, however, has remained elusive so far. Since during phylogeny, Borrelia DNA has led to multiple germ-line mutations within the CB1 candidate gene for schizophrenia, a meta analysis has been performed of all papers on schizophrenic birth excesses with no less than 3000 cases each. All published numerical data were then plotted against the seasonal distributions of Ixodes ticks worldwide. Results In the United States, Europe and Japan the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodes ticks nine months earlier at the time of conception. South of the Wallace Line, which limits the spread of Ixodes ticks and Borrelia burgdorferi into Australia, seasonal trends are less significant, and in Singapore, being non-endemic for Ixodes ticks and Lyme disease, schizophrenic birth excesses are absent. Conclusion At present, it cannot be excluded that prenatal infection by B. burgdorferi is harmful to the implanting human blastocyst. The epidemiological clustering of sporadic schizophrenia by season and locality rather emphasises the risk to the unborn of developing a congenital, yet preventable brain disorder later in life. PMID:12453316

  14. 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.

  15. Maxillary sporadic Burkitt's lymphoma associated with neuro-orbital involvement in an Indian male

    PubMed Central

    Manne, Rakesh Kumar; Madu, Chandra Sekhar; Talla, Harsh Vardhan

    2014-01-01

    Burkitt's lymphoma (BL) is the fastest growing malignancy of the lymphoreticular system to affect humans and has a potential ability to double in size every day. A case of maxillary sporadic BL (sBL) associated with neuro-orbital involvement in an Indian male is presented. sBL initially presented as maxillary swelling with no obvious dental and periodontal changes. Histological specimen from incisional biopsy revealed a round cell malignant tumor and immunohistochemistry reactions favored nonHodgkin's lymphoma consistent with BL. Four weeks later, patient presented with orbital involvement as diplopia, sixth cranial nerve palsy, and medial rectus palsy. Chemotherapy regimen according to LMB 89 protocol was started. During chemotherapy regimen patient showed bradycardia and Babinski response, suggestive of central nervous system involvement. sBL associated with orbital involvement is extremely rare and only seven cases have been reported. Our case showed unusual presentation; despite the aggressive tumor did not show any common clinical, radiological, and hematological findings. We also discussed the role of oral medicine specialist, importance of early diagnosis, and prompt referral in management of maxillary sBL. PMID:24963253

  16. Differential expression of molecular motors in the motor cortex of sporadic ALS.

    PubMed

    Pantelidou, Maria; Zographos, Spyros E; Lederer, Carsten W; Kyriakides, Theodore; Pfaffl, Michael W; Santama, Niovi

    2007-06-01

    The molecular mechanisms underlying the selective neurodegeneration of motor neurons in amyotrophic lateral sclerosis (ALS) are inadequately understood. Recent breakthroughs have implicated impaired axonal transport, mediated by molecular motors, as a key element for disease onset and progression. The current work identifies the expression of 15 kinesin-like motors in healthy human motor cortex, including three novel isoforms. Our comprehensive quantitative mRNA analysis in control and sporadic ALS (SALS) motor cortex specimens detects SALS-specific down-regulation of KIF1Bbeta and novel KIF3Abeta, two isoforms we show to be enriched in the brain, and also of SOD1, a key enzyme linked to familial ALS. This is accompanied by a marked reduction of KIF3Abeta protein levels. In the motor cortex KIF3Abeta localizes in cholinergic neurons, including upper motor neurons. No mutations causing splicing defects or altering protein-coding sequences were identified in the genes of the three proteins. The present study implicates two motor proteins as possible candidates in SALS pathology. PMID:17418584

  17. [A case of a syndrome resembling PSP after aortic arch replacement under deep hypothermic circulatory arrest].

    PubMed

    Sakiyama, Yusuke; Michizono, Kumiko; Tomari, Shinya; Watanabe, Osamu; Nakahara, Keiichi; Takashima, Hiroshi

    2011-01-01

    A 57-year-old man presented with acute signs and symptoms mimicking PSP (bradykinesia, supranuclear ocular palsy, dysphagia, neck dystonia, and apraxic gait) on the day after a graft replacement surgery, which was performed for aortic arch aneurysm under deep hypothermic circulatory arrest (rectal temperature, 18 degrees C). Dysphagia improved temporarily, but relapsed after a few months. Symptoms did not change during 2 years of antiparkinsonian drug administration. Brain images obtained before the surgery revealed slight atrophy of the midbrain tegmentum and frontal lobes, but the patient was asymptomatic. No findings of cerebral vascular disease and hypoxic encephalopathy were observed on brain images after the surgery. These clinical features resembling PSP might have been caused by deep hypothermia and the patient's predisposition for PSP. This is the first case report in Japan of a syndrome resembling PSP that occurred after aortic arch replacement under deep hypothermic circulatory arrest. PMID:21387699

  18. 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

  19. 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. PMID:26840342

  20. 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

  1. 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. PMID:24766340

  2. Global sporadic E rates as derived from GPS radio occultation measurements

    NASA Astrophysics Data System (ADS)

    Arras, Christina; Jacobi, Christoph; Wickert, Jens; Heise, Stefan

    The low-Earth orbiting satellites CHAMP, GRACE and the FORMOSAT-3/COSMIC constel-lation provide in total about 2,500 globally distributed GPS radio occultation (RO) measure-ments per day. This fosters substantial studies of atmospheric parameters on a global scale in a high spatial resolution. Due to the fact that GPS signals are highly sensitive to sharp electron density gradients in ionospheric altitudes, the radio occultation technique is a valuable tool for detecting sporadic E layers occurring in the lower ionosphere. Sporadic E layers, themselves, are localised patches of relatively high electron density in the E-region ionosphere which cause strong amplitude scintillations in GPS signals. This characteristic is used to derive information on sporadic E occurrence from radio occultation data. Based on the combined CHAMP, GRACE and COSMIC RO data set, we derive a global distribution of sporadic E occurrence rates enabling us to investigate their seasonal variation. It is generally accepted that sporadic E is caused through neutral wind shear inducing a vertical motion to ions and electrons. It has frequently been proposed that this formation process is enhanced for increased dip angles and a stronger horizontal magnetic field component. We compared our global distribution of sporadic E occurrence rates with magnetic field predictions from the International Geomagnetic Reference Field (IGRF) and can confirm experimentally these theoretical aspects in midlatitudes.

  3. 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.

  4. 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

  5. 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

  6. 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

    2015-01-01

    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. PMID:25596565

  7. 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

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

    PubMed

    Allen, David J; Trainor, Eamonn; 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

  9. Intrinsic Brain Activity of Cognitively Normal Older Persons Resembles More That of Patients Both with and at Risk for Alzheimer's Disease Than That of Healthy Younger Persons

    PubMed Central

    Pasquini, Lorenzo; Tonch, Annika; Plant, Claudia; Zherdin, Andrew; Ortner, Marion; Kurz, Alexander; Förstl, Hans; Zimmer, Claus; Grimmer, Timo; Wohlschäger, Afra; Riedl, Valentin

    2014-01-01

    Abstract In Alzheimer's disease (AD), recent findings suggest that amyloid-β (Aβ)-pathology might start 20–30 years before first cognitive symptoms arise. To account for age as most relevant risk factor for sporadic AD, it has been hypothesized that lifespan intrinsic (i.e., ongoing) activity of hetero-modal brain areas with highest levels of functional connectivity triggers Aβ-pathology. This model induces the simple question whether in older persons without any cognitive symptoms intrinsic activity of hetero-modal areas is more similar to that of symptomatic patients with AD or to that of younger healthy persons. We hypothesize that due to advanced age and therefore potential impact of pre-clinical AD, intrinsic activity of older persons resembles more that of patients than that of younger controls. We tested this hypothesis in younger (ca. 25 years) and older healthy persons (ca. 70 years) and patients with mild cognitive impairment and AD-dementia (ca. 70 years) by the use of resting-state functional magnetic resonance imaging, distinct measures of intrinsic brain activity, and different hierarchical clustering approaches. Independently of applied methods and involved areas, healthy older persons' intrinsic brain activity was consistently more alike that of patients than that of younger controls. Our result provides evidence for larger similarity in intrinsic brain activity between healthy older persons and patients with or at-risk for AD than between older and younger ones, suggesting a significant proportion of pre-clinical AD cases in the group of cognitively normal older people. The observed link of aging and AD with intrinsic brain activity supports the view that lifespan intrinsic activity may contribute critically to the pathogenesis of AD. PMID:24689864

  10. Charge on luminous bodies resembling natural ball lightning produced via electrical arcs through lump silicon.

    PubMed

    Porter, Christina L; Miley, Galen P; Griffiths, David J; Sánchez, Erik

    2014-12-01

    A phenomenon resembling natural ball lightning can be produced via electrical arcing through silicon. We use lump silicon instead of silicon wafers to achieve higher production rates and larger, longer-lived luminous balls than previously reported. The luminous balls consist of a silicon core surrounded by a porous network of loosely bound silicon dioxide nanoparticles. We find that the balls carry a small net charge on the order of 10(-12) C and propose that the nanoparticles are electrostatically bound to the core due to this charge. PMID:25615201