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Sample records for adult-onset slowly progressive

  1. A nonsense mutation of human XRCC4 is associated with adult-onset progressive encephalocardiomyopathy

    PubMed Central

    Bee, Leonardo; Nasca, Alessia; Zanolini, Alice; Cendron, Filippo; d'Adamo, Pio; Costa, Rodolfo; Lamperti, Costanza; Celotti, Lucia; Ghezzi, Daniele; Zeviani, Massimo

    2015-01-01

    We studied two monozygotic twins, born to first cousins, affected by a multisystem disease. At birth, they both presented with bilateral cryptorchidism and malformations. Since early adulthood, they developed a slowly progressive neurological syndrome, with cerebellar and pyramidal signs, cognitive impairment, and depression. Dilating cardiomyopathy is also present in both. By whole-exome sequencing, we found a homozygous nucleotide change in XRCC4 (c.673C>T), predicted to introduce a premature stop codon (p.R225*). XRCC4 transcript levels were profoundly reduced, and the protein was undetectable in patients' skin fibroblasts. XRCC4 plays an important role in non-homologous end joining of DNA double-strand breaks (DSB), a system that is involved in repairing DNA damage from, for example, ionizing radiations. Gamma-irradiated mutant cells demonstrated reduction, but not abolition, of DSB repair. In contrast with embryonic lethality of the Xrcc4 KO mouse, nonsense mutations in human XRCC4 have recently been associated with primordial dwarfism and, in our cases, with adult-onset neurological impairment, suggesting an important role for DNA repair in the brain. Surprisingly, neither immunodeficiency nor predisposition to malignancy was reported in these patients. PMID:25872942

  2. Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

    PubMed

    Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

    2016-06-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging. PMID:26962957

  3. A nursing challenge: adult-onset Tay-Sachs disease.

    PubMed

    Hamilton, D

    1991-12-01

    Adult-onset GM2 gangliosidosis (AOG), also labelled Adult-Onset Tay-Sachs disease, is a slowly progressing disease caused by a gradual accumulation of the GM2 ganglioside in neurons due to defective hexosaminidase A. Recent research findings and clinical experiences suggest that AOG may be more widespread than previously believed. Moreover, the diagnosis of AOG is often delayed because patients present with psychotic symptoms that mimic dementia, schizophrenia, mania, and depression. Because AOG patients typically respond poorly to psychiatric drug therapy and the symptomatology is so diverse, nurses must design and implement nursing care that ensures safety, structure, and comfort. PMID:1759864

  4. Adult onset retinoblastoma.

    PubMed

    Sengupta, Sabyasachi; Pan, Utsab; Khetan, Vikas

    2016-07-01

    Retinoblastoma (RB) is the most common primary malignant intraocular tumor of childhood presenting usually before 5 years of age. RB in adults older than 20 years is extremely rare. A literature search using PubMed/PubMed Central, Scopus, Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date. Over the past decade, there has been a significant increase in the number of such reports, indicating heightened level of suspicion among ophthalmologists. Compared to its pediatric counterpart, adult onset RB poses unique challenges in diagnosis and treatment. This article summarizes available literature on adult onset RB and its clinical and pathologic profile, genetics, association with retinocytoma, diagnostics, treatment, and outcomes. PMID:27609158

  5. [A man with slowly progressive dyspnea on exertion].

    PubMed

    Lauren, S T; Simons, S O; Arens, A I J

    2016-01-01

    A 42-year-old man with a medical history of liver cirrhosis and portal hypertension was admitted to the hospital because of slowly progressive shortness of breath and hypoxemia. The diagnosis hepatopulmonary syndrome was confirmed by a pulmonary perfusion scan with 99m Tc-albumin. The scan showed a right-left shunt, because the 99m Tc-albumin transited the lungs and appeared in the brain, the thyroid gland, the kidneys and the spleen. The patient received a liver transplantation, which is considered the only definitive treatment. PMID:27484427

  6. Acute Progression of Adult-Onset Atypical Hemolytic-Uremic Syndrome due to CFH Mutation: A Case Report

    PubMed Central

    Sikorska, Dorota; Hoppe, Krzysztof; Schwermer, Krzysztof; Oko, Andrzej

    2013-01-01

    Atypical hemolytic-uremic syndrome (aHUS), unlike typical HUS, is not due to bacteria but rather to an idiopathic or genetic cause that promotes dysregulation of the alternative complement pathway. It leads to hemolytic anemia, thrombocytopenia, and renal impairment. Although aHUS secondary to a genetic mutation is relatively rare, when occurring due to a mutation in Factor H (CFH), it usually presents with younger onset and has a more severe course, which in the majority ends with end-stage renal failure. Paradoxically to most available data, our case features acute aHUS due to a CFH mutation with late onset (38-year-old) and rapid progression to end-stage renal disease. Due to current data indicating a high risk of graft failure in such patients, the diagnosis of aHUS secondary to a genetic cause has disqualified our patient from a living (family) donor renal transplantation and left her with no other option but to begin permanent renal replacement therapy. PMID:24558625

  7. Adult-Onset Hypogonadism.

    PubMed

    Khera, Mohit; Broderick, Gregory A; Carson, Culley C; Dobs, Adrian S; Faraday, Martha M; Goldstein, Irwin; Hakim, Lawrence S; Hellstrom, Wayne J G; Kacker, Ravi; Köhler, Tobias S; Mills, Jesse N; Miner, Martin; Sadeghi-Nejad, Hossein; Seftel, Allen D; Sharlip, Ira D; Winters, Stephen J; Burnett, Arthur L

    2016-07-01

    In August 2015, an expert colloquium commissioned by the Sexual Medicine Society of North America (SMSNA) convened in Washington, DC, to discuss the common clinical scenario of men who present with low testosterone (T) and associated signs and symptoms accompanied by low or normal gonadotropin levels. This syndrome is not classical primary (testicular failure) or secondary (pituitary or hypothalamic failure) hypogonadism because it may have elements of both presentations. The panel designated this syndrome adult-onset hypogonadism (AOH) because it occurs commonly in middle-age and older men. The SMSNA is a not-for-profit society established in 1994 to promote, encourage, and support the highest standards of practice, research, education, and ethics in the study of human sexual function and dysfunction. The panel consisted of 17 experts in men's health, sexual medicine, urology, endocrinology, and methodology. Participants declared potential conflicts of interest and were SMSNA members and nonmembers. The panel deliberated regarding a diagnostic process to document signs and symptoms of AOH, the rationale for T therapy, and a monitoring protocol for T-treated patients. The evaluation and management of hypogonadal syndromes have been addressed in recent publications (ie, the Endocrine Society, the American Urological Association, and the International Society for Sexual Medicine). The primary purpose of this document was to support health care professionals in the development of a deeper understanding of AOH, particularly in how it differs from classical primary and secondary hypogonadism, and to provide a conceptual framework to guide its diagnosis, treatment, and follow-up. PMID:27343020

  8. Niemann-Pick type C: focus on the adolescent/adult onset form.

    PubMed

    Di Lazzaro, Vincenzo; Marano, Massimo; Florio, Lucia; De Santis, Stefano

    2016-11-01

    Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment. PMID:26998855

  9. Slowly progressive Lemierre's syndrome with orbital pain and exophthalmos.

    PubMed

    Hama, Yuka; Koga, Masatoshi; Fujinami, Jun; Asayama, Shinya; Toyoda, Kazunori

    2016-01-01

    Lemierre's syndrome is an oropharyngeal bacterial infection characterized by rapidly progressive septic thrombophlebitis of the internal jugular vein. A lack of appropriate antibiotic therapy can be life-threatening. We describe the case of a 39-year-old man with Lemierre's syndrome who presented with long-lasting orbital pain and acute exophthalmos 6 weeks after initial infection. This report is to help clinicians consider the diagnosis of Lemierre's syndrome when encountering a patient with long-lasting orbital pain and acute exophthalmos. Neck ultrasonography is useful for detecting thrombophlebitis of the internal jugular vein in Lemierre's syndrome patients. PMID:26419364

  10. Rapidly Versus Slowly Progressing Patients With Alzheimer's Disease: Differences in Baseline Cognition.

    PubMed

    Seidl, Jennifer N Travis; Massman, Paul J

    2016-06-01

    Rate of progression of cognitive deficits is variable among patients with Alzheimer's disease (AD). The purpose of the current study was to compare demographic characteristics and performance on neuropsychological measures at baseline evaluation between rapidly and slowly progressing patients. Participants were divided into 2 groups based on change in Alzheimer's Disease Assessment Scale-Cognitive subscale score from baseline to 2-year follow-up, and baseline performance was compared between the groups. Participants were 55 rapidly progressing and 55 slowly progressing patients with probable AD who had a follow-up evaluation 21 to 27 months after the baseline evaluation. The groups differed in age and initial Clinical Dementia Rating. Performance differed significantly between the groups on Verbal Series Attention Test time, Logical Memory I, Visual Reproduction I, Block Design, and Controlled Oral Word Association Test. Differences were found between rapidly and slowly progressing patients on baseline neuropsychological testing. PMID:26646117

  11. Slowly progressive anarthria with late anterior opercular syndrome: a variant form of frontal cortical atrophy syndromes.

    PubMed

    Broussolle, E; Bakchine, S; Tommasi, M; Laurent, B; Bazin, B; Cinotti, L; Cohen, L; Chazot, G

    1996-12-01

    We describe eight patients with slowly progressive speech production deficit combining speech apraxia, dysarthria, dysprosody and orofacial apraxia, and initially no other deficit in other language and non-language neuropsychological domains. Long-term follow-up (6-10 years) in 4 cases showed an evolution to muteness, bilateral suprabulbar paresis with automatic-voluntary dissociation and frontal lobe cognitive slowing without generalised intellectual deterioration. Most disabled patients presented with an anterior opercular syndrome (Foix-Chavany-Marie syndrome), and pyramidal or extrapyramidal signs. CT and MRI findings disclosed asymmetric (left > right) progressive cortical atrophy of the frontal lobes predominating in the posterior inferior frontal region, notably the operculum. SPECT and PET revealed a decreased cerebral blood flow and metabolism, prominent in the left posterior-inferior frontal gyrus and premotor cortex, extending bilaterally in the most advanced cases. Pathological study of two cases showed non-specific neuronal loss, gliosis, and spongiosis of superficial cortical layers, mainly confined to the frontal lobes, with no significant abnormalities in the basal ganglia, thalamus, cerebellum, brain stem (except severe neuronal loss in the substantia nigra in one case), and spinal cord. We propose to call this peculiar syndrome Slowly Progressive Anarthria (SPA), based on its specific clinical presentation, and its metabolic and pathological correlates. SPA represents another clinical expression of focal cortical degeneration syndromes, that may overlap with other similar syndromes, specially primary progressive aphasia and the various frontal lobe dementias. PMID:8994103

  12. LH Dynamics in Overweight Girls with Premature Adrenarche and Slowly Progressive Sexual Precocity

    PubMed Central

    Bordini, Brian; Littlejohn, Elizabeth; Rosenfield, Robert L.

    2010-01-01

    Background. Excess adiposity and premature adrenarche (PA) are risk factors for the development of polycystic ovary syndrome (PCOS). Methods. Girls with slowly progressive precocious breast development, who were overweight and had PA (SPPOPA, 6.2–8.2 years, n = 5), overweight PA (6.6–10.8 years, n = 7), and overweight premenarcheal controls (OW-PUB, 10.6–12.8 years, n = 8) underwent hormonal sleep testing and GnRH agonist (GnRHag) and ACTH tests. Results. Despite an insignificant sleep-related increase in LH and prepubertal baseline hormone levels, SPPOPA peak LH and estradiol responses to GnRHag were intermediate between those of PA and OW-PUB, the LH being significantly different from both. Conclusions. GnRHag tests indicate that SPPOPA is a slowly progressive form of true puberty with blunted LH dynamics. These results argue against the prepubertal hyperandrogenism of excess adiposity or PA enhancing LH secretion or causing ovarian hyperandrogenism prior to menarche. Excess adiposity may contribute to both the early onset and slow progression of puberty. PMID:20886012

  13. Adult onset xanthogranuloma presenting as laryngeal mass.

    PubMed

    Li, Shawn; Weidenbecher, Mark

    2016-01-01

    Histiocytic disorders can be classified according to the distribution pattern of the lesions and the organs involved. Non-Langerhans-cell histiocytosis is a rare group of diseases that have varied clinical presentations ranging from isolated masses to diffuse systemic eruptions. We discuss a patient who initially presented with a vocal cord lesion and was ultimately diagnosed with adult onset xanthogranuloma. PMID:26954863

  14. Expanding the spectrum of PEX10-related peroxisomal biogenesis disorders: slowly progressive recessive ataxia.

    PubMed

    Renaud, Mathilde; Guissart, Claire; Mallaret, Martial; Ferdinandusse, Sacha; Cheillan, David; Drouot, Nathalie; Muller, Jean; Claustres, Mireille; Tranchant, Christine; Anheim, Mathieu; Koenig, Michel

    2016-08-01

    Peroxisomal biogenesis disorders (PBDs) consist of a heterogeneous group of autosomal recessive diseases, in which peroxisome assembly and proliferation are impaired leading to severe multisystem disease and early death. PBDs include Zellweger spectrum disorders (ZSDs) with a relatively mild clinical phenotype caused by PEX1, (MIM# 602136), PEX2 (MIM# 170993), PEX6 (MIM# 601498), PEX10 (MIM# 602859), PEX12 (MIM# 601758), and PEX16 (MIM# 603360) mutations. Three adult patients are reported belonging to a non-consanguineous French family affected with slowly progressive cerebellar ataxia, axonal neuropathy, and pyramidal signs. Mental retardation and diabetes mellitus were optional. The age at onset was in childhood or in adolescence (3-15 years). Brain MRI showed marked cerebellar atrophy. Biochemical blood analyses suggested a mild peroxisomal defect. With whole exome sequencing, two mutations in PEX10 were found in the three patients: c.827G>T (novel) causing the missense change p.Cys276Phe and c.932G>A causing the missense change p.Arg311Gln. The phenotypic spectrum related to PEX10 mutations includes slowly progressive, syndromic recessive ataxia. PMID:27230853

  15. Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome: a slowly progressive disorder with stereotypical presentation.

    PubMed

    Cazzato, Daniele; Bella, Eleonora Dalla; Dacci, Patrizia; Mariotti, Caterina; Lauria, Giuseppe

    2016-02-01

    Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a newly described condition with onset in adulthood, characterized by progressive balance impairment and sensory disturbances in the lower limbs, which can severely affect patients' quality of life. Its pathogenesis remains obscure and the diagnosis challenging. We described four patients complaining of slowly progressive gait unbalance and sensory disturbances at the feet followed, after a period ranging 2-6 years, by cerebellar dysfunction. All patients showed gait and limb ataxia, positive Romberg sign, cerebellar dysarthria, gaze-evoked nystagmus, absent deep tendon reflexes, and impaired vibratory sensation. Nerve conduction studies revealed axonal sensory neuropathy, brain magnetic resonance imaging showed cerebellar atrophy, and otoneurological investigation demonstrated bilateral vestibular areflexia with impaired vestibulo-ocular reflexes. The diagnosis of CANVAS should be suspected on clinical ground based on homogeneous course of symptoms and signs, and addressed by video-oculography eye movement recording. PMID:26566912

  16. [Cerebro-oculo-hepato-renal syndrome (Arima's syndrome) with slowly progressive renal insufficiency and epilepsy].

    PubMed

    Kubota, M; Shinozaki, M; Ishizaki, A; Kurata, K

    1991-11-01

    We reported an additional case of Arima's syndrome with slowly progressive renal insufficiency and epilepsy. The patient is a 20-year-old man whose parents are consanguineous. He had a history of mild asphyxia at birth, and unexplained tachypnea developed during the neonatal period. But it disappeared later, and he have had no respiratory problem since then. Physical examination on admission at the age of 19 years revealed bilateral blephaloptosis, narrow palate, searching nystagmoid movement, absence of light reflex, muscle hypotonia and wasting of extremities. Funduscopic study showed optic hypoplasia, choroid coloboma and narrowing of vessels. Head CT scan showed agenesis of cerebellar vermis and hypoplasia of brainstem. CT scan and echography of the kidney disclosed the bilateral multiple cysts. Liver was hyperechoic in echographic study; this finding is consistent with fatty change. EEG showed dysrhythmic slow wave activity with sporadic spike and wave complex. Compared with previously reported cases, the present case has the following features: (1) slowly progressive renal insufficiency, (2) generalized tonic clonic convulsion developing from the age of 11 months, (3) ABR abnormalities including the right-sided shortening of wave I-II interpeak latency and bilateral ill-defined wave V. Slow progress of renal failure in our case may reflect the mild pathological process of the kidney with sparing functional nephrons. It shows the diversity of the kidney pathology in Arima's syndrome. Epilepsy is a less common association in the syndrome, whereas EEG abnormalities were reported. ABR abnormalities may reflect the morphological alteration of the brainstem structure including auditory pathway. In our case it is uncertain whether the neonatal tachypnea was due to birth asphyxia or brainstem malformation responsible for abnormal respiration as suggested in Joubert's syndrome. PMID:1760207

  17. Biallelic Mutations in DNM1L are Associated with a Slowly Progressive Infantile Encephalopathy.

    PubMed

    Nasca, Alessia; Legati, Andrea; Baruffini, Enrico; Nolli, Cecilia; Moroni, Isabella; Ardissone, Anna; Goffrini, Paola; Ghezzi, Daniele

    2016-09-01

    Mitochondria are highly dynamic organelles, undergoing continuous fission and fusion, and mitochondrial dynamics is important for several cellular functions. DNM1L is the most important mediator of mitochondrial fission, with a role also in peroxisome division. Few reports of patients with genetic defects in DNM1L have been published, most of them describing de novo dominant mutations. We identified compound heterozygous DNM1L variants in two brothers presenting with an infantile slowly progressive neurological impairment. One variant was a frame-shift mutation, the other was a missense change, the pathogenicity of which was validated in a yeast model. Fluorescence microscopy revealed abnormally elongated mitochondria and aberrant peroxisomes in mutant fibroblasts, indicating impaired fission of these organelles. In conclusion, we described a recessive disease caused by DNM1L mutations, with a clinical phenotype resembling mitochondrial disorders but without any biochemical features typical of these syndromes (lactic acidosis, respiratory chain complex deficiency) or indicating a peroxisomal disorder. PMID:27328748

  18. Atypical, slowly progressive behavioral variant frontotemporal dementia associated with C9ORF72 hexanucleotide expansion

    PubMed Central

    Khan, Baber K.; Yokoyama, Jennifer S.; Takada, Leonel T.; Sha, Sharon J.; Rutherford, Nicola. J.; Fong, Jamie C.; Karydas, Anna; Wu, Teresa; Ketelle, Robin; Baker, Matt C.; Hernandez, Mariely-Dejesus; Coppola, Giovanni; Geschwind, Daniel H.; Rademakers, Rosa; Lee, Suzee E.; Rosen, Howard J.; Rabinovici, Gil D.; Seeley, William; Rankin, Katherine P.; Boxer, Adam L.; Miller, Bruce L.

    2012-01-01

    Background Some patients meeting behavioral variant frontotemporal dementia (bvFTD) diagnostic criteria progress slowly and plateau at mild symptom severity. Such patients have mild neuropsychological and functional impairments, lack characteristic bvFTD brain atrophy, and have thus been referred to as bvFTD “phenocopies” or slowly progressive (bvFTD-SP). The few patients with bvFTD-SP that have been studied at autopsy have found no evidence of FTD pathology, suggesting that bvFTD-SP is neuropathologically distinct from other forms of FTD. Here, we describe two patients with bvFTD-SP with chromosome 9 open reading frame 72 (C9ORF72) hexanucleotide expansions. Methods Three hundred and eighty-four patients with FTD clinical spectrum and Alzheimer’s disease diagnoses were screened for C9ORF72 expansion. Two bvFTD-SP mutation carriers were identified. Neuropsychological and functional data, as well as brain atrophy patterns assessed using voxel-based morphometry (VBM), were compared with 44 patients with sporadic bvFTD and 85 healthy controls. Results Both patients were age 48 at baseline and met possible bvFTD criteria. In the first patient, VBM revealed thalamic and posterior insula atrophy. Over seven years, his neuropsychological performance and brain atrophy remained stable. In the second patient, VBM revealed cortical atrophy with subtle frontal and insular volume loss. Over two years, her neuropsychological and functional scores as well as brain atrophy remained stable. Conclusions C9ORF72 mutations can present with a bvFTD-SP phenotype. Some bvFTD-SP patients may have neurodegenerative pathology, and C9ORF72 mutations should be considered in patients with bvFTD-SP and a family history of dementia or motor neuron disease. PMID:22399793

  19. Phenocopy or variant: a longitudinal study of very slowly progressive frontotemporal dementia

    PubMed Central

    Brodtmann, Amy; Cowie, Tiffany; McLean, Catriona; Darby, David

    2013-01-01

    Frontal variant frontotemporal dementia (fvFTD) can present with a range of social and cognitive impairments. Complicating this clinical picture is a group of non-progressive or ‘phenocopy’ patients. We present a patient and his father with very slowly progressive fvFTD over decades. Stable MRI and positron emission tomography (PET) imaging abnormalities were present in the presenting patient, with serial neuropsychological assessments that showed no significant change over 15 years. His father also had a 20-year history of functional decline, associated with neuropsychological evidence of change. Neuropathological confirmation of the condition of his father became available. This revealed gross bilateral frontal atrophy and spongiosis in the frontal cortical regions with mild neuronal loss and rounded ubiquitinated perinuclear inclusions, consistent with early stage frontotemporal lobar degeneration with ubiquitin by current neuropathological criteria. The phenotype of frontal variant FTD is broad. Many patients present with frontal networks dysfunction. We present evidence that some patients with a very slow clinical progression do have FTD. PMID:23391955

  20. Adult onset retinoblastoma: A diagnostic dilemma.

    PubMed

    Raj, Amit; Arya, Sudesh Kumar; Punia, Rajpal Singh; Kohli, Piyush

    2016-01-01

    Retinoblastoma is the most common intraocular tumor of childhood. About 95% of retinoblastoma cases are diagnosed before the age of 5 years. Not more than 30 cases of Adult-onset retinoblastoma have been reported in literature. A 32 year old male presented with a painful blind eye. There was sudden loss of vision accompanied by severe pain and redness in right eye about 1 year ago, for which some surgery was done with neither a gain in vision nor any relief from pain. Then he was put on maximum tolerable medical therapy, later cyclocryotherapy was done. Now he presented to us with complains of extreme pain and bleeding from right eye since 2 days. There is no history of any ocular trauma. Right eye had no perception of light & showed anterior staphyloma with perforation. Right eye evisceration was done & material sent for histopathological examination, which revealed an adult-onset retinoblastoma. CECT scan revealed thickening of optic nerve throughout its entire length with contrast enhancement. He was further taken up for enucleation of residual sclera with maximum optic nerve stump removal to reconfirm the diagnosis. Histopathological examination revealed tumor deposits present in orbital soft tissue, resection margins and optic nerve cut end.Retinoblastoma presenting in adult age creates a diagnostic dilemma because of its low frequency and atypical features. We want to highlight the importance of high clinical suspicion and imaging modalities before taking any patient for evisceration with unexplained vision loss. One should send the eviscerated material for histopathological examination. PMID:26709674

  1. Phenotypes, Risk Factors, and Mechanisms of Adult-Onset Asthma

    PubMed Central

    Ilmarinen, Pinja; Tuomisto, Leena E.; Kankaanranta, Hannu

    2015-01-01

    Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Genetic factors, atopy, and early respiratory tract infections are well-recognized factors predisposing to childhood-onset asthma. Adult-onset asthma is more often associated with obesity, smoking, depression, or other life-style or environmental factors, even though genetic factors and respiratory tract infections may also play a role in adult-onset disease. Adult-onset asthma is characterized by absence of atopy and is often severe requiring treatment with high dose of inhaled and/or oral steroids. Variety of risk factors and nonatopic nature of adult-onset disease suggest that variety of mechanisms is involved in the disease pathogenesis and that these mechanisms differ from the pathobiology of childhood-onset asthma with prevailing Th2 airway inflammation. Recognition of the mechanisms and mediators that drive the adult-onset disease helps to develop novel strategies for the treatment. The aim of this review was to summarize the current knowledge on the pathogenesis of adult-onset asthma and to concentrate on the mechanisms and mediators involved in establishing adult-onset asthma in response to specific risk factors. We also discuss the involvement of these mechanisms in the currently recognized phenotypes of adult-onset asthma. PMID:26538828

  2. Late-adult onset Leigh syndrome.

    PubMed

    McKelvie, Penelope; Infeld, Bernard; Marotta, Rosetta; Chin, Judy; Thorburn, David; Collins, Steven

    2012-02-01

    We report an illustrative case of a 74-year-old man who, in the absence of intercurrent illness, presented with rapid cognitive decline. MRI showed bilateral, symmetrical, high T2-weighted signal in the anterior basal ganglia and medial thalami, extending to the periaqueductal grey matter, basal ganglia and basal frontal lobes. A (18)F-fluorodeoxyglucose-positron emission tomography scan showed widespread reduction of metabolism in the cortex of the frontal, temporal and parietal lobes, posterior cingulate gyrus, precuneus and caudate nuclei, with sparing of the sensorimotor cortex, thalami and lentiform nuclei. A mild vitamin B12 deficiency was found and despite normal thiamine levels, intravenous (IV) thiamine and vitamin B therapy was commenced, with a short course of IV methylprednisolone and tetracycline. Repeat neuropsychological assessment four weeks following treatment revealed increased alertness and interactiveness but significant cognitive decline persisted. Unexpectedly, the patient suffered a transmural anterior myocardial infarction six weeks after presentation and died within 24hours. An a autopsy showed: global reduction in cytochrome oxidase (COX) activity in all skeletal muscles examined; bilateral, symmetrical, hypervascular, focally necrotizing lesions in the substantia nigra, periaqueductal grey matter, superior colliculi, medial thalami anteriorly and posteriorly, as well as in the putamena but the mammillary bodies were not affected. Biochemical analysis of fresh muscle confirmed selective deficiency of complex IV of the oxidative phosphorylation chain. A diagnosis of late-adult onset Leigh syndrome was made. Multiple genetic studies failed to identify the specific underlying mutation. The relevant literature is reviewed. PMID:22273117

  3. A case of slowly progressive anti-Yo-associated paraneoplastic cerebellar degeneration successfully treated with antitumor and immunotherapy.

    PubMed

    Tsuboguchi, Shintaro; Yajima, Ryuji; Higuchi, You; Ishikawa, Masanori; Kawachi, Izumi; Koyama, Yu; Nishizawa, Masatoyo

    2016-07-28

    We report a case of slowly progressive anti-Yo-associated paraneoplastic cerebellar degeneration (PCD) with breast cancer in a 54-year-old woman. The symptoms of limb and truncal ataxia, and dysarthria gradually progressed during the course of 1 year, and the modified Rankin scale (mRS) score was 2. A mastectomy with sentinel lymph node resection was performed for the breast cancer. No malignant cells were found on histopathological examination of the lymph node. Combination chemotherapy with adriamycin and cyclophosphamide (AC) prevented neurologic deterioration. However, subsequent treatment with trastuzumab and paclitaxel did not prevent progression of the symptoms (mRS score 3). Brain magnetic resonance imaging showed atrophy of the cerebellar hemispheres without brain stem atrophy. Anti-Yo antibody was detected in the serum, which led to a diagnosis of anti-Yo-associated PCD. We resected an enlarged axillary lymph node, which was found on computed tomography. The histopathological analysis of the lymph node revealed foreign body granuloma, which suggested an association with necrotic malignant tissue. Following additional tegafur-uracil therapy and two courses of intravenous immunoglobulin (IVIg), the cerebellar signs and symptoms gradually improved (mRS score 2). The clinical course shows that PCD can present as a slowly progressive cerebellar symptom. We propose an active treatment for anti-Yo-associated PCD consisting of tumor resection, combined chemotherapy, and IVIg. PMID:27356731

  4. Adult-onset Satoyoshi syndrome and response to plasmapheresis

    PubMed Central

    Aghoram, Rajeshwari; Srijithesh, P. R.; Kannoth, Sudheeran

    2016-01-01

    Satoyoshi syndrome is a rare disease characterized by alopecia, recurrent muscle spasms, diarrhea, and skeletal abnormalities Adult-onset disease is reported only in five patients. Most of the reports have not characterized the nature of muscle spasm in the disease. In this paper, we report the first case of adult-onset Satoyoshi syndrome from India and the clinical and electrophysiological response to plasmapheresis. PMID:27011647

  5. Unusual sequelae of adult-onset dermatomyositis

    PubMed Central

    Naffaa, Mohammad Ebrahim; Bishara, Rema; Braun-Moscovici, Yolanda; Balbir-Gurman, Alexandra

    2014-01-01

    A 44-year-old woman diagnosed with dermatomyositis 5 years ago based on progressive proximal muscle weakness, elevated creatine kinase, typical findings on electromyography and muscle biopsy. Despite the treatment, in contrast to improvement in her muscle symptoms, the heliotrope rash of her eyelids persisted. After several years, the patient developed multiple limited skin retraction lesions with hyperpigmentation on both lower limbs. Palpation of these lesions revealed dry, cold and very firm skin on both thighs and calves, particularly in the distal areas. X-ray and ultrasound imaging of the calves showed multiple subcutaneous calcifications in the distal muscles. PMID:25085949

  6. Adult-onset laryngomalacia: case reports and review of management.

    PubMed

    Hey, Shi Ying; Oozeer, Nashreen Banon; Robertson, Stuart; MacKenzie, Kenneth

    2014-12-01

    Laryngomalacia is a dynamic airway condition characterised by inward collapse of flaccid supraglottic structures during inspiration. Although the most common cause of stridor in the paediatric population, adult-onset laryngomalacia remains a rare entity and its management, challenging. Two cases of adult-onset laryngomalacia are reported. A review of the English literature is performed and additional publications identified by hand-searching relevant papers; 13 case reports/series comprising 28 cases of adult-onset laryngomalacia were identified, divided into two main groups: idiopathic (6/28) and acquired (22/28). The aetiology of the acquired form includes neurological, traumatic and iatrogenic. Reported therapeutic measures used are laser supraglottoplasty, epiglottopexy, partial epiglottidectomy, defunctioning tracheostomy and intubation whilst correcting the underlying cause. The majority of patients only required one therapeutic procedure (follow-up of 2-24 months). A strong index of suspicion is required to diagnose adult-onset laryngomalacia aided by in-office laryngoscopy. The rarity of this condition prevents management-based randomised controlled trials. PMID:24615649

  7. Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

    PubMed

    Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

    2016-07-01

    Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466

  8. Etiopathogenesis and Therapeutic Approach to Adult Onset Acne

    PubMed Central

    Kaur, Sarabjit; Verma, Poonam; Sangwan, Ankita; Dayal, Surabhi; Jain, Vijay Kumar

    2016-01-01

    Acne vulgaris is usually considered as a skin disorder that primarily affects adolescents reaching a peak at the age of 14–17 years in females and 16–19 years in males. However, recent epidemiologic studies have shown that a significant number of female patients aged >25 years experience acne. As it is regarded as a disease of teenagers, adults are more apprehensive and experience social anxiety. Hence, adult onset acne has become a matter of concern. PMID:27512185

  9. Etiopathogenesis and Therapeutic Approach to Adult Onset Acne.

    PubMed

    Kaur, Sarabjit; Verma, Poonam; Sangwan, Ankita; Dayal, Surabhi; Jain, Vijay Kumar

    2016-01-01

    Acne vulgaris is usually considered as a skin disorder that primarily affects adolescents reaching a peak at the age of 14-17 years in females and 16-19 years in males. However, recent epidemiologic studies have shown that a significant number of female patients aged >25 years experience acne. As it is regarded as a disease of teenagers, adults are more apprehensive and experience social anxiety. Hence, adult onset acne has become a matter of concern. PMID:27512185

  10. Office Work Exposures and Adult-Onset Asthma

    PubMed Central

    Jaakkola, Maritta S.; Jaakkola, Jouni J.K.

    2007-01-01

    Background Office exposures have been linked to symptoms of sick building syndrome, but their relation to the development of asthma has not been studied previously. These exposures have increasing importance because an increasing proportion of the workforce is working in office environments. Objectives The aim of this study was to assess the relations of exposure to carbonless copy paper (CCP), paper dust, and fumes from photocopiers and printers to adult-onset asthma. Methods We conducted a population-based incident case–control study of adults 21–63 years of age living in the Pirkanmaa District in South Finland. All new clinically diagnosed cases (n = 521) of asthma were recruited during a 3-year study period. A random sample of the source population formed the controls (n = 1,016). This part focused on 133 cases and 316 controls who were office workers according to their current occupation classified by the 1988 International Standard Classification of Occupations. All participants answered a questionnaire on health, smoking, occupation, and exposures at work and home. Subjects with previous asthma were excluded. Results Exposures to paper dust [adjusted odds ratio (OR) = 1.97; 95% confidence interval (CI), 1.25–3.10] and CCP (OR = 1.66; 95% CI, 1.03–2.66) were related to significantly increased risk of adult-onset asthma. An exposure–response relation was observed between exposure to paper dust and risk of asthma. Conclusions This study provides new evidence that exposures to paper dust and CCP in office work are related to increased risk of adult-onset asthma. Reduction of these exposures could prevent asthma in office workers. Clinicians seeing asthma patients should be aware of this link to office exposures. PMID:17637914

  11. Season of Birth and Risk for Adult Onset Glioma

    PubMed Central

    Efird, Jimmy T.

    2010-01-01

    Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive. PMID:20623001

  12. [Macrophage activation syndrome associated with adult-onset Still's disease].

    PubMed

    Iwamoto, Masahiro

    2007-12-01

    Macrophage activation syndrome (MAS) is a rare and potentially lethal disease, resulting from uncontrolled activation and proliferation of T lymphocytes and macrophages. Adult-onset Still's disease (AOSD) is an inflammatory disease. AOSD resemble reactive MAS in its symptoms and laboratory data. Moreover, AOSD per se induces MAS. It is, therefore, quite difficult to differentiate these syndrome and disease. The immunodeficiency state induced by treatment in AOSD could reactivate latent viruses such as Epstein-Barr virus, which could potentially lead to MAS. The therapeutic agents for AOSD, such as sulfasalazine, also could provoke reactive MAS. Because multiple factors are involved in inducing MAS to a different degree, the main cause should be searched for and targeted for the therapy. PMID:18174671

  13. Diagnosis of congenital and adult-onset hypothyroidism in cats.

    PubMed

    Greco, Deborah S

    2006-02-01

    Whereas hyperthyroidism is the most common endocrine disorder in the cat, hypothyroidism is the least common feline endocrine disorder. This is a the result of several factors including low index of suspicion, rarity of the naturally occurring hypothyroidism in cats, and a lack of species specific tests for endogenous TSH and antithyroglobulin antibodies. Nonetheless, hypothyroidism does occur in cats, especially in kittens and after radioactive treatment for hyperthyroidism. The clinician should become familiar with the common presentations of congenital and adult-onset hypothyroidism in cats. In addition, some of the tests specific to dogs (such as endogenous canine TSH) may be utilized to diagnose subclinical hypothyroidism in cats. Fortunately, the treatment of feline hypothyroidism with synthetic levothyroxine is both straightforward and effective. PMID:16584030

  14. Refractory Genital HPV Infection and Adult-Onset Still Disease

    PubMed Central

    Yu, Xin; Zheng, Heyi

    2016-01-01

    Abstract Adult-onset Still disease (AOSD) is a systemic autoimmune disease (AIID) that can develop after exposure to infectious agents. Genital human papillomavirus (HPV) infection has been reported to induce or exacerbate AIIDs, such as systemic lupus erythematosus (SLE). No guidelines are available for the management of genital warts in AOSD. Case report and literature review. We report a patient who was diagnosed AOSD in the setting of refractory and recurrent genital HPV infection, demonstrating a possible link between HPV infection and AOSD. In addition, we also discuss the management of genital warts in patients with AOSD. To the best of our knowledge, no previous cases of AOSD with genital HPV infection have been reported in literature. We then conclude that the patient AOSD may be triggered by primary HPV infection. Larger number of patient samples is needed to confirm whether HPV could trigger AOSD. PMID:27082556

  15. Comparing illness presentation, treatment and functioning between patients with adolescent- and adult-onset psychosis.

    PubMed

    Hui, Christy Lai-Ming; Li, Adrienne Wing-Yee; Leung, Chung-Ming; Chang, Wing-Chung; Chan, Sherry Kit-Wa; Lee, Edwin Ho-Ming; Chen, Eric Yu-Hai

    2014-12-30

    Studies have shown that early- and adult-onset schizophrenia patients differ in pre-morbid traits, illness presentation, psychopathology, and prognosis. We aimed to compare adult-onset patients (age range 26-55 years) with an adolescent-onset cohort (15-25 years) in demographics, illness presentation and functioning at baseline. Participants were from two territory-wide early intervention services for adolescent-onset (n=671) and adult-onset psychosis patients (n=360) in Hong Kong. The adolescent-onset cohort had their initial psychotic episode from 2001-2003; retrospective data collection was done through systematic case note review. The adult-onset cohort was recruited for a larger interventional study from 2009-2011; information was collected via face-to-face interviews. Adult-onset psychosis was significantly associated with more females, more smokers, more non-local birth, more full-time employment, better functioning, poorer medication adherence, more psychiatric hospitalization and fewer with schizophrenia than adolescent-onset psychosis (mean age: 20.4). The effect sizes were small, except for medication adherence where a robust effect was found. No group difference in DUP was found. The finding that adult-onset patients had better functioning challenges the view that adolescent- and adult-onset psychoses share a similar prognostic trajectory. Implications for adapting intervention processes for adolescent- and adult-onset psychosis are discussed. PMID:25238985

  16. Warming up Improves Speech Production in Patients with Adult Onset Myotonic Dystrophy

    ERIC Educational Resources Information Center

    de Swart, B.J.M.; van Engelen, B.G.M.; Maassen, B.A.M.

    2007-01-01

    This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls…

  17. Adult-onset foveomacular vitelliform dystrophy: A fresh perspective.

    PubMed

    Chowers, Itay; Tiosano, Liran; Audo, Isabelle; Grunin, Michelle; Boon, Camiel J F

    2015-07-01

    Adult-onset foveomacular vitelliform dystrophy (AFVD) was first described by Gass four decades ago. AFVD is characterized by subretinal vitelliform macular lesions and is usually diagnosed after the age of 40. The lesions gradually increase and then decrease in size over the years, leaving an area of atrophic outer retina and retinal pigment epithelium. This process is accompanied by a loss of visual acuity. Vitelliform lesions are hyperautofluorescent and initially have a dome-shaped appearance on optical coherence tomography. The electro-oculogram and full-field electroretinogram are typically normal, indicating localized retinal pathology. Phenocopies are also associated with other ocular disorders, such as vitreomacular traction, age-related macular degeneration, pseudodrusen, and central serous chorioretinopathy. A minority of AFVD patients have a mutation in the PRPH2, BEST1, IMPG1, or IMPG2 genes. A single-nucleotide polymorphism in the HTRA1 gene has also been associated with this phenotype. Accordingly, the phenotype can arise from alterations in the photoreceptors, retinal pigment epithelium, and/or interphotoreceptor matrix depending on the underlying gene defect. Excess photoreceptor outer segment production and/or impaired outer segment uptake due to impaired phagocytosis are likely underlying mechanisms. At present, no cure is available for AFVD. Thus, the current challenges in the field include identifying the underlying cause in the majority of AFVD cases and the development of effective therapeutic approaches. PMID:25681578

  18. Efficacy of Anakinra in Refractory Adult-Onset Still's Disease

    PubMed Central

    Ortiz-Sanjuán, Francisco; Blanco, Ricardo; Riancho-Zarrabeitia, Leyre; Castañeda, Santos; Olivé, Alejandro; Riveros, Anne; Velloso-Feijoo, María.L.; Narváez, Javier; Jiménez-Moleón, Inmaculada; Maiz-Alonso, Olga; Ordóñez, Carmen; Bernal, José A.; Hernández, María V.; Sifuentes-Giraldo, Walter A.; Gómez-Arango, Catalina; Galíndez-Agirregoikoa, Eva; Blanco-Madrigal, Juan; Ortiz-Santamaria, Vera; del Blanco-Barnusell, Jordi; De Dios, Juan R.; Moreno, Mireia; Fiter, Jordi; Riscos, Marina de los; Carreira, Patricia; Rodriguez-Valls, María J.; González-Vela, M. Carmen; Calvo-Río, Vanesa; Loricera, Javier; Palmou-Fontana, Natalia; Pina, Trinitario; Llorca, Javier; González-Gay, Miguel A.

    2015-01-01

    Abstract Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2–6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3–47.5] mg/day at ANK onset to 5 [0–10] at 12 months. After a median [IQR] follow-up of 16 [5–50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations. PMID:26426623

  19. Memory Loss and Frontal Cognitive Dysfunction in a Patient with Adult-onset Neuronal Intranuclear Inclusion Disease.

    PubMed

    Araki, Kunihiko; Sone, Jun; Fujioka, Yusuke; Masuda, Michihito; Ohdake, Reiko; Tanaka, Yasuhiro; Nakamura, Tomohiko; Watanabe, Hirohisa; Sobue, Gen

    2016-01-01

    Neuronal intranuclear inclusion disease (NIID) is an uncommon progressive neurodegenerative disorder. Adult-onset NIID can result in prominent dementia. We herein describe the case of a 74-year-old man who presented with dementia, cerebellar ataxia, neuropathy, and autonomic dysfunction. Diffusion-weighted imaging showed hyperintensity of the corticomedullary junction. Fluid-attenuated inversion recovery images showed frontal-dominant white matter hyperintensity. NIID was diagnosed from the presence of intranuclear inclusions in a skin biopsy sample. Neuropsychological testing revealed memory loss and frontal cognitive dysfunction, especially in relation to language and executive functions. We were therefore able to confirm the association of NIID with cognitive dysfunction. PMID:27523009

  20. Pathologic staging of white matter lesions in adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids.

    PubMed

    Alturkustani, Murad; Keith, Julia; Hazrati, Lili-Naz; Rademakers, Rosa; Ang, Lee-Cyn

    2015-03-01

    The pathologic features of adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids (ALAS) are variable, and this has led to different hypotheses as to whether primarily demyelination or axonopathy may underlie this disorder. Typical ALAS pathology is rarely accompanied by focal multiple sclerosis (MS)-like plaques. In ALAS pathology accompanied by focal multiple sclerosis (MS)-like plaques cases, the pathologic features cannot be distinguished from those of progressive MS with diffusely abnormal white matter. To clarify these issues, we examined neuropathologic features in 159 representative samples from 5 ALAS cases (3 men and 2 women aged 39-61 years) and in 95 representative samples from 3 chronic MS cases (1 man and 2 women aged 50-73 years). The white matter abnormalities in ALAS cases were characterized by 3 evolving stages: 1) white matter with numerous spheroids in a background of well-myelinated fibers; 2) moderate loss of myelinated fibers with sparse to moderate number of spheroids; and 3) leukodystrophy-like pattern of confluent axonal and myelin loss. The application of this staging system suggests that myelin loss in ALAS is preceded by axonopathy. In progressive MS cases, the diffusely abnormal white matter pathology could be attributed to both primary demyelination and axonopathy. Some cases with predominant axonopathy are difficult to distinguish from cases with ALAS. PMID:25668567

  1. Genetics Home Reference: adult-onset leukoencephalopathy with axonal spheroids and pigmented glia

    MedlinePlus

    ... it causes a severe decline in thinking and reasoning abilities (dementia). Over time, motor skills are affected, ... Schmahmann JD. Adult onset leukodystrophy with neuroaxonal spheroids: clinical, neuroimaging and neuropathologic observations. Brain Pathol. 2009 Jan; ...

  2. [Adult onset Still's disease with the initial symptom of pharyngalgia: a case report].

    PubMed

    Zhou, Enhui; Chen, Xiaoping; Zhang, Jingfei

    2015-09-01

    Adult onset Still's disease is a rare inflammatory disease characterized by spiking fevers, arthritis/ arthralgias, typical salmon-colored bumpy rash, pharyngalgia, myalgia and possible involvement of visceral organs. The diagnosis is exclusively based on clinical symptoms, according to the criteria, after the exclusion of well-known infectious, neoplastic, or other autoimmune/autoinflammatory disorders. This report includes one case of adult onset Still's disease with the initial symptom of pharyngalgia. PMID:26647549

  3. Targeting Hsp90/Hsp70-based protein quality control for treatment of adult onset neurodegenerative diseases.

    PubMed

    Pratt, William B; Gestwicki, Jason E; Osawa, Yoichi; Lieberman, Andrew P

    2015-01-01

    Currently available therapies for adult onset neurodegenerative diseases provide symptomatic relief but do not modify disease progression. Here we explore a new neuroprotective approach based on drugs targeting chaperone-directed protein quality control. Critical target proteins that unfold and aggregate in these diseases, such as the polyglutamine androgen receptor in spinal and bulbar muscular atrophy, huntingtin in Huntington's disease, α-synuclein in Parkinson's disease, and tau in Alzheimer's disease, are client proteins of heat shock protein 90 (Hsp90), and their turnover is regulated by the protein quality control function of the Hsp90/Hsp70-based chaperone machinery. Hsp90 and Hsp70 have opposing effects on client protein stability in protein quality control; Hsp90 stabilizes the clients and inhibits their ubiquitination, whereas Hsp70 promotes ubiquitination dependent on CHIP (C terminus of Hsc70-interacting protein) and proteasomal degradation. We discuss how drugs that modulate proteostasis by inhibiting Hsp90 function or promoting Hsp70 function enhance the degradation of the critical aggregating proteins and ameliorate toxic symptoms in cell and animal disease models. PMID:25292434

  4. Cathepsin F mutations cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis

    PubMed Central

    Smith, Katherine R.; Dahl, Hans-Henrik M.; Canafoglia, Laura; Andermann, Eva; Damiano, John; Morbin, Michela; Bruni, Amalia C.; Giaccone, Giorgio; Cossette, Patrick; Saftig, Paul; Grötzinger, Joachim; Schwake, Michael; Andermann, Frederick; Staropoli, John F.; Sims, Katherine B.; Mole, Sara E.; Franceschetti, Silvana; Alexander, Noreen A.; Cooper, Jonathan D.; Chapman, Harold A.; Carpenter, Stirling; Berkovic, Samuel F.; Bahlo, Melanie

    2013-01-01

    Kufs disease, an adult-onset neuronal ceroid lipofuscinosis, is challenging to diagnose and genetically heterogeneous. Mutations in CLN6 were recently identified in recessive Kufs disease presenting as progressive myoclonus epilepsy (Type A), whereas the molecular basis of cases presenting with dementia and motor features (Type B) is unknown. We performed genome-wide linkage mapping of two families with recessive Type B Kufs disease and identified a single region on chromosome 11 to which both families showed linkage. Exome sequencing of five samples from the two families identified homozygous and compound heterozygous missense mutations in CTSF within this linkage region. We subsequently sequenced CTSF in 22 unrelated individuals with suspected recessive Kufs disease, and identified an additional patient with compound heterozygous mutations. CTSF encodes cathepsin F, a lysosomal cysteine protease, dysfunction of which is a highly plausible candidate mechanism for a storage disorder like ceroid lipofuscinosis. In silico modeling suggested the missense mutations would alter protein structure and function. Moreover, re-examination of a previously published mouse knockout of Ctsf shows that it recapitulates the light and electron-microscopic pathological features of Kufs disease. Although CTSF mutations account for a minority of cases of type B Kufs, CTSF screening should be considered in cases with early-onset dementia and may avoid the need for invasive biopsies. PMID:23297359

  5. Health-related quality of life in sporadic adult-onset ataxia.

    PubMed

    Abele, Michael; Klockgether, Thomas

    2007-02-15

    Despite progressive disability in sporadic adult-onset ataxia (SAOA), little is known about patients' assessment of their ataxic disorder and its impact on health-related quality of life (Hr-QoL). This study investigated Hr-QoL by means of the following self-administered scales: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Beck Depression Inventory (BDI), and the Medical Outcome Study Short Form (SF-36). Twenty-two unselected ataxia patients were included. Sleep-related complaints were found in 9 (41%) of 22 and symptoms of depression in 6 (38%) of 16 patients. Compared to a large german control group, SAOA patients had lower scores in all SF-36 dimensions except for bodily pain. The greatest impairment was found in the domain physical functioning, followed by the domains social functioning and role limitations (emotional problems). There was a significant negative correlation of all nonmotor SF-36 dimensions with the BDI score. Walking aid dependency was significantly correlated with poorer health status perception in several motor and nonmotor domains. In addition, impaired sleep quality was correlated with an impaired general health perception and with bodily pain. The study demonstrates a great impact of SAOA on Hr-QoL. Adequate treatment of depression, motor disability, and impaired sleep quality is essential to improve Hr-QoL in ataxic patients. PMID:17149704

  6. A slowly progressive form of limb-girdle muscular dystrophy type 2C associated with founder mutation in the SGCG gene in Puerto Rican Hispanics

    PubMed Central

    Al-Zaidy, Samiah A; Malik, Vinod; Kneile, Kelley; Rosales, Xiomara Q; Gomez, Ana Maria; Lewis, Sarah; Hashimoto, Sayaka; Gastier-Foster, Julie; Kang, Peter; Darras, Basil; Kunkel, Louis; Carlo, Jose; Sahenk, Zarife; Moore, Steven A; Pyatt, Robert; Mendell, Jerry R

    2015-01-01

    Limb-girdle muscular dystrophy type 2C (LGMD2C) is considered one of the severe forms of childhood-onset muscular dystrophy. The geographical distribution of founder mutations in the SGCG gene has a prominent effect on the prevalence of LGMD2C in certain populations. The aim of this study was to confirm the hypothesis that the c.787G>A (p.E263K) mutation in the SGCG gene is a founder mutation among Puerto Rican Hispanics and to characterize the associated clinical and immunohistochemical phenotype. Genotyping of six polymorphic microsatellite markers internal to (D13S232) and flanking (D13S175, D13S292, D13S787, D13S1243, D13S283) the SGCG gene was performed on four unrelated Puerto Rican patients with LGMD2C. Preserved ambulation to the second decade of life was observed in at least two subjects. Immunostaining of skeletal muscle demonstrated absence of γ-sarcoglycan in all affected subjects. Two markers, D13S232 and D13S292, were highly informative and confirmed that all four families share the haplotype of the mutant allele. Our findings confirm that the E263K missense mutation in the SGCG gene is a founder mutation in Puerto Rican Hispanics. A slowly progressive disease course with prolonged preservation of ambulation can be seen in association with this mutation, providing evidence for phenotypic variability. PMID:25802879

  7. Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats

    PubMed Central

    Mustroph, M.L.; King, M.A.; Klein, R.L.; Ramirez, J.J.

    2012-01-01

    Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer’s disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics. PMID:22561128

  8. Adult-Onset Still's Disease and Cardiac Tamponade: A Rare Association

    PubMed Central

    Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes

    2015-01-01

    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity. PMID:26175648

  9. Sandhoff disease mimicking adult-onset bulbospinal neuronopathy.

    PubMed

    Thomas, P K; Young, E; King, R H

    1989-09-01

    A 32 year old male is described with an onset of upper limb postural tremor in adolescence followed by muscle cramps. Progressive proximal amyotrophy and weakness in the limbs developed late in the third decade. Examination disclosed, in addition, bilateral facial weakness and mild dysarthria. Enzyme studies revealed hexosaminidase A and B deficiency, indicating a diagnosis of Sandhoff disease. Intra-axonal membranocytoplasmic bodies were present in a rectal biopsy. The presentation, which resembled that of X-linked bulbospinal neuronopathy, widens the clinical spectrum for disorders related to G(M2) gangliosidosis. PMID:2795083

  10. Generation of a novel mouse model that recapitulates early and adult onset glycogenosis type IV.

    PubMed

    Akman, H Orhan; Sheiko, Tatiana; Tay, Stacey K H; Finegold, Milton J; Dimauro, Salvatore; Craigen, William J

    2011-11-15

    Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen branching enzyme (GBE). The diagnostic feature of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age of disease onset. Absence of enzyme activity is lethal in utero or in infancy affecting primarily muscle and liver. However, residual enzyme activity (5-20%) leads to juvenile or adult onset of a disorder that primarily affects muscle as well as central and peripheral nervous system. Here, we describe two mouse models of GSD IV that reflect this spectrum of disease. Homologous recombination was used to insert flippase recognition target recombination sites around exon 7 of the Gbe1 gene and a phosphoglycerate kinase-Neomycin cassette within intron 7, leading to a reduced synthesis of GBE. Mice bearing this mutation (Gbe1(neo/neo)) exhibit a phenotype similar to juvenile onset GSD IV, with wide spread accumulation of PG. Meanwhile, FLPe-mediated homozygous deletion of exon 7 completely eliminated GBE activity (Gbe1(-/-)), leading to a phenotype of lethal early onset GSD IV, with significant in utero accumulation of PG. Adult mice with residual GBE exhibit progressive neuromuscular dysfunction and die prematurely. Differently from muscle, PG in liver is a degradable source of glucose and readily depleted by fasting, emphasizing that there are structural and regulatory differences in glycogen metabolism among tissues. Both mouse models recapitulate typical histological and physiological features of two human variants of branching enzyme deficiency. PMID:21856731

  11. Is Adolescent-Onset First-Episode Psychosis Different from Adult Onset?

    ERIC Educational Resources Information Center

    Ballageer, Trevor; Malla, Ashok; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

    2005-01-01

    Objective: To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). Method: Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated…

  12. Adult-Onset Antisocial Behavior Trajectories: Associations with Adolescent Family Processes and Emerging Adulthood Functioning

    ERIC Educational Resources Information Center

    Mata, Andrea D.; van Dulmen, Manfred H. M.

    2012-01-01

    Guided by conceptual and empirical work on emerging adulthood, this study investigated the role of closeness to mother and father and behavioral autonomy during adolescence on the development of adult-onset antisocial behavior. Using data from the National Longitudinal Study of Adolescent Health (Add Health), we identified four aggressive…

  13. Stroke prevention by direct revascularization for patients with adult-onset moyamoya disease presenting with ischemia.

    PubMed

    Kim, Tackeun; Oh, Chang Wan; Kwon, O-Ki; Hwang, Gyojun; Kim, Jeong Eun; Kang, Hyun-Seung; Cho, Won-Sang; Bang, Jae Seung

    2016-06-01

    . CONCLUSIONS Direct or combined revascularization for patients with adult-onset moyamoya disease presenting with ischemia can prevent further stroke. PMID:26636391

  14. Adult-onset Still's disease as a mask of Hodgkin lymphoma

    PubMed Central

    Pawlak-Buś, Katarzyna; Leszczyński, Piotr

    2015-01-01

    Adult-onset Still's disease is a rare disorder, which creates difficulties in making a proper diagnosis. Ambiguous symptoms and results of auxiliary tests, lack of unequivocal diagnostic tests and the need to exclude other causes of the disease are major problems in clinical practice. A case of a 22-year-old woman with dominated recurrent fever, significantly elevated inflammation markers and arthritis is presented. Based on clinical signs after exclusion of infection, hematological and other reasons, the patient was diagnosed with adult-onset Still's disease. Standard treatment, with high doses of glucocorticoids and a disease-modifying drug, was applied, without the anticipated effects. The diagnostic tests were conducted again due to the lack of clinical improvement, increase of inflammatory markers and unusual response to treatment. A new symptom of significance, i.e. mediastinal lymphadenopathy, was found. After the histopathological examination of lymph nodes, Hodgkin's disease was diagnosed and targeted therapy for hematological malignancy was applied.

  15. The juvenile-onset, adolescent-onset and adult-onset obese.

    PubMed

    Garn, S M; Sullivan, T V; Hawthorne, V M

    1991-02-01

    As shown in more than 8000 proband-parent pairs derived from a total-community sample and followed in longitudinal fashion, the 5-year incidence of obesity (new cases per 5-year period) approximates 8 percent for the juvenile-onset, adolescent-onset and adult-onset obese alike. Parents of juvenile-onset (ages 5-9), adolescent-onset (10-19) and adult-onset obese (20-39) tend to be of above-average fatness level, +0.25Z scores, overall, regardless of the age at onset of obesity in their progeny. Except for the parents of the juvenile-onset obese, educational level of the parents tends to be below average for the sample as a whole. These new data acquired in longitudinal context and explored in retrospective-prospective fashion do not substantiate the notion that different onset ages of obesity indicate separate etiologies and different family constellations. PMID:2040547

  16. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q

    SciTech Connect

    Wirtz, M.K.; Samples, J.R.; Kramer, P.L.

    1997-02-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-on-set primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 57 refs., 3 figs., 3 tabs.

  17. Urticaria and dermographism in patients with adult-onset Still's disease.

    PubMed

    Criado, Paulo Ricardo; de Carvalho, Jozélio Freire; Ayabe, Liliane Akemi; Brandt, Hebert Roberto Clivati; Romiti, Ricardo; Maruta, Celina W

    2012-08-01

    Adult-onset Still's disease (AOSD) patients typically present with arthralgia, fever, lymphadenopathy and a transient salmon maculopapular rash. Only approximately 25 cases of AOSD with urticaria were described in the literature. In this article, the authors report three additional cases of AOSD with urticarial and dermographic lesions who had a good clinical response to glucocorticoid and antihistamines. A review of the literature concerning this issue is also herein written. PMID:21785958

  18. Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

    PubMed

    Bir, Shyamal C; Patra, Devi Prasad; Maiti, Tanmoy K; Sun, Hai; Guthikonda, Bharat; Notarianni, Christina; Nanda, Anil

    2016-09-01

    OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database. PMID:27581317

  19. Adult onset unilateral systematized porokeratotic eccrine ostial and dermal duct nevus: a case report.

    PubMed

    Bandoyopadhyay, Debabrata; Saha, Abanti

    2014-06-01

    Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is an uncommon, benign dermatosis that is characterized by asymptomatic grouped keratotic papules and plaques with a linear pattern on the extremities with distinct porokeratotic histopathological features. The lesions usually appear at birth or in childhood, although rare cases of late-onset adult PEODDN have been described. Herein we report a case of adult onset PEODDN with unilateral and segmental involvement. PMID:24945650

  20. Intra-arterial Chemotherapy for Adult Onset Retinoblastoma in a 32-Year-Old Man.

    PubMed

    Magan, Tejal; Khoo, Chloe T L; Jabbour, Pascal M; Fuller, Dwain G; Shields, Carol L

    2016-01-01

    A 32-year-old man with active unilateral group D retinoblastoma that was recurrent following external beam radiotherapy was treated with intra-arterial chemotherapy, leading to tumor regression. Additional plaque radiotherapy and intravitreal chemotherapy were required for complete control. Final visual acuity was 20/40. In selected cases, adult-onset retinoblastoma can be managed with intra-arterial chemotherapy. [J Pediatr Ophthalmol Strabismus. 2016;53:e43-e46.]. PMID:27486894

  1. Adult-onset Still's disease revealed by perimyocarditis and a concomitant reactivation of an EBV infection

    PubMed Central

    Meckenstock, Roderich; Therby, Audrey; Gibault-Genty, Geraldine; Khau, David; Monnier, Sebastien; Greder-Belan, Alix

    2012-01-01

    We describe a 17-year-old patient presenting perimyocarditis as the initial manifestation of the adult-onset Still's disease. Corticotherapy was rapidly successful but induced major acute hepatitis in relation with Epstein-Barr virus reactivation. After 1 year, even if the global outcome is favourable, a slightly lowered ejection fraction still persists. Former case reports and differential diagnosis with reactive haemophagocytic syndrome would be discussed. PMID:23166163

  2. Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

    PubMed

    Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

    2016-07-01

    Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis. PMID:27021143

  3. Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations

    PubMed Central

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K.

    2012-01-01

    Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PMID:23049995

  4. Globus pallidus deep brain stimulation for adult-onset axial dystonia

    PubMed Central

    Shaikh, Aasef G.; Mewes, Klaus; Jinnah, H.A.; DeLong, Mahlon R.; Gross, Robert E.; Triche, Shirley; Freeman, Alan; Factor, Stewart A.

    2016-01-01

    Introduction Generalized dystonia, both primary and secondary forms, and axial dystonias such as tardive dystonia, and idiopathic cervical dystonia are responsive to globus pallidus interna (GPi) DBS. There is a paucity of investigations probing the impact of DBS on adult-onset axial dystonia. We assessed the efficacy of GPi DBS in four patients with rare adult-onset axial dystonia. Methods Primary outcome measure was improvement in the motor component of the Burke-Fahn-Marsden (BFM) rating scale. Secondary outcome measures were quality of life as determined by the SF-36 questionnaire, time to achieve best possible benefit and DBS parameters that accounted for the best response. In patients with prominent concomitant cervical dystonia we also used the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Results GPi DBS improved BFM scores by 87.63 ± 11.46%. Improvement in total severity scale of TWSTRS was 71.5 ± 12.7%. Quality of life also remarkably improved as evidenced by 109.38 ± 82.97 and 7.05 ± 21.48% percent change in psychometrically-based physical component summary (PCS), and a mental component summary (MCS) score respectively. Conclusions GPi DBS is a very effective treatment for adult-onset axial dystonia. Considering its refractoriness to medical therapy and significant impact on quality of life DBS should be considered for this disorder. PMID:25260969

  5. Pesticide Methoxychlor Promotes the Epigenetic Transgenerational Inheritance of Adult-Onset Disease through the Female Germline

    PubMed Central

    Manikkam, Mohan; Haque, M. Muksitul; Guerrero-Bosagna, Carlos; Nilsson, Eric E.; Skinner, Michael K.

    2014-01-01

    Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. PMID:25057798

  6. The Incidence and Clinical Characteristics of Adult-Onset Convergence Insufficiency

    PubMed Central

    Ghadban, Rafif; Martinez, Jennifer M.; Diehl, Nancy N.; Mohney, Brian G.

    2015-01-01

    Objective The purpose of this study was to describe the clinical characteristics and natural history of convergence insufficiency (CI) in a population-based cohort of adults. Design Retrospectively reviewed population-based cohort. Participants Adult (≥19 years of age) residents of Olmsted County, Minnesota. Methods The medical records of all adults diagnosed with CI over a 20-year period were retrospectively reviewed. Main outcome measures Clinical characteristics and outcomes for adult-onset convergence insufficiency. Results A total of 118 adults (annual incidence of 8.44 per 100 000 patients older than 19 years) were diagnosed with CI during the 20-year period, comprising 15.7% of all forms of adult-onset strabismus observed in this population. The median age at diagnosis was 68.5 years (range 21.7 to 97.1 years) and 68 (57.6%) were female. The mean initial exodeviation at near was 14.1 PD (range 1 to 30 PD) and 1.7 PD (range 0 to 10 PD) at distance. The Kaplan-Meier rate of exotropia increasing by 7 prism diopters or more at near over time was 4.2% at 5 years, 13.5% at 10 years, and 24.4% at 20 years. Approximately 88% were managed with prisms while less than 5% underwent surgical correction. Conclusions Adult-onset convergence insufficiency comprised approximately 1 in 6 adults who were newly diagnosed with strabismus in this 20-year cohort. There was a significant increase in incidence with increasing age. Nearly one-fourth had an increase of their near exodeviation of at least 7 PD by 20 years after their diagnosis and most patients were managed conservatively. PMID:25626756

  7. Bartonella henselae infection presenting with a picture of adult-onset Still's disease.

    PubMed

    Durey, Areum; Kwon, Hea Yoon; Im, Jae-Hyoung; Lee, Sun Myoung; Baek, JiHyeon; Han, Seung Baik; Kang, Jae-Seung; Lee, Jin-Soo

    2016-05-01

    We report a patient with a clinical picture of suggestive for adult-onset Still's Disease (ASOD) due to Bartonella infection. A 42-year-old immunocompetent man was admitted with fever, rash, arthralgia and sore throat. As his clinical picture suggested ASOD except unusual skin manifestation, we treated him on steroid and ibuprofen. His fever and constitutional symptoms responded immediately within 24hrs of commencing therapy, yet rash and leukocytosis remained. Meanwhile, Bartonella infection was proved by culture of bone marrow. Minocyclin treatment started combined with hydroxychloroquine sulfate and the patient discharged with overall improvement. PMID:27000538

  8. Adult Onset Still's Disease: A Review on Diagnostic Workup and Treatment Options

    PubMed Central

    Gopalarathinam, Rajesh; Orlowsky, Eric; Kesavalu, Ramesh; Yelaminchili, Sreeteja

    2016-01-01

    Adult onset Still's disease (AOSD) is a rare systemic inflammatory disease of unknown etiology and pathogenesis that presents in 5 to 10% of patients as fever of unknown origin (FUO) accompanied by systemic manifestations. We report an interesting case of a 33-year-old African-American male who presented with one-month duration of FUO along with skin rash, sore throat, and arthralgia. After extensive workup, potential differential diagnoses were ruled out and the patient was diagnosed with AOSD based on the Yamaguchi criteria. The case history, incidence, pathogenesis, clinical manifestations, differential diagnoses, diagnostic workup, treatment modalities, and prognosis of AOSD are discussed in this case report. PMID:27042373

  9. Cord Blood Transplantation Following Reduced-intensity Conditioning for Adult-onset Inherited Hemophagocytic Lymphohistiocytosis.

    PubMed

    Kuriyama, Takuro; Kato, Koji; Sakamoto, Keiji; Hayashi, Masayasu; Takashima, Shuichiro; Mori, Yasuo; Takenaka, Katsuto; Iwasaki, Hiromi; Teshima, Takanori; Harada, Naoki; Nagafuji, Koji; Miyamoto, Toshihiro; Akashi, Koichi

    2016-01-01

    Inherited hemophagocytic lymphohistiocytosis (HLH) is a genetic anomaly disorder in which abnormally activated cytotoxic T lymphocytes cannot induce the apoptosis of target cells and antigen-presenting cells, leading to hemophagocytosis, pancytopenia, and a variety of symptoms such as a high fever. The present patient with adult-onset HLH developed refractory disease despite receiving immunosuppressive treatments. He underwent a reduced-intensity conditioning (RIC) regimen that comprised antithymocyte globulin (ATG) followed by cord blood transplantation (RIC-CBT). He achieved and maintained a complete donor type. The incorporation of ATG into RIC-CBT may prevent graft failure and control hemophagocytosis, however, further efforts are necessary to reduce infectious complications. PMID:26984088

  10. Herpes Zoster Meningitis Complicating Combined Tocilizumab and Cyclosporine Therapy for Adult-Onset Still's Disease

    PubMed Central

    Tsurukawa, Shinichiro; Iwanaga, Nozomi; Izumi, Yasumori; Shirakawa, Atsunori; Kawahara, Chieko; Shukuwa, Tetsuo; Inamoto, Miwako; Kawakami, Atsushi; Migita, Kiyoshi

    2016-01-01

    A 56-year-old female with refractory adult-onset Still's disease presented with ocular herpes zoster infection during TCZ treatment. After three days of acyclovir treatment (5 mg/kg), she developed a severe headache and high fever. Viral DNA isolation and cerebral spinal fluid abnormalities led to a herpes zoster meningitis diagnosis. Her meningitis was cured by high doses of intravenous acyclovir (10 mg/kg for 14 days). To our knowledge, this is the first report of meningeal herpes zoster infection in rheumatic diseases under TCZ treatment. PMID:27092286

  11. Herpes Zoster Meningitis Complicating Combined Tocilizumab and Cyclosporine Therapy for Adult-Onset Still's Disease.

    PubMed

    Tsurukawa, Shinichiro; Iwanaga, Nozomi; Izumi, Yasumori; Shirakawa, Atsunori; Kawahara, Chieko; Shukuwa, Tetsuo; Inamoto, Miwako; Kawakami, Atsushi; Migita, Kiyoshi

    2016-01-01

    A 56-year-old female with refractory adult-onset Still's disease presented with ocular herpes zoster infection during TCZ treatment. After three days of acyclovir treatment (5 mg/kg), she developed a severe headache and high fever. Viral DNA isolation and cerebral spinal fluid abnormalities led to a herpes zoster meningitis diagnosis. Her meningitis was cured by high doses of intravenous acyclovir (10 mg/kg for 14 days). To our knowledge, this is the first report of meningeal herpes zoster infection in rheumatic diseases under TCZ treatment. PMID:27092286

  12. Response to immunotherapy in a patient with adult onset Leigh syndrome and T9176C mtDNA mutation.

    PubMed

    Chuquilin, Miguel; Govindarajan, Raghav; Peck, Dawn; Font-Montgomery, Esperanza

    2016-09-01

    Leigh syndrome is a mitochondrial disease caused by mutations in different genes, including ATP6A for which no known therapy is available. We report a case of adult-onset Leigh syndrome with response to immunotherapy. A twenty year-old woman with baseline learning difficulties was admitted with progressive behavioral changes, diplopia, headaches, bladder incontinence, and incoordination. Brain MRI and PET scan showed T2 hyperintensity and increased uptake in bilateral basal ganglia, respectively. Autoimmune encephalitis was suspected and she received plasmapheresis with clinical improvement. She was readmitted 4 weeks later with dysphagia and aspiration pneumonia. Plasmapheresis was repeated with resolution of her symptoms. Given the multisystem involvement and suggestive MRI changes, genetic testing was done, revealing a homoplasmic T9176C ATPase 6 gene mtDNA mutation. Monthly IVIG provided clinical improvement with worsening when infusions were delayed. Leigh syndrome secondary to mtDNA T9176C mutations could have an autoimmune mechanism that responds to immunotherapy. PMID:27408822

  13. Mutations in DNAJC5, Encoding Cysteine-String Protein Alpha, Cause Autosomal-Dominant Adult-Onset Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Nosková, Lenka; Stránecký, Viktor; Hartmannová, Hana; Přistoupilová, Anna; Barešová, Veronika; Ivánek, Robert; Hůlková, Helena; Jahnová, Helena; van der Zee, Julie; Staropoli, John F.; Sims, Katherine B.; Tyynelä, Jaana; Van Broeckhoven, Christine; Nijssen, Peter C.G.; Mole, Sara E.; Elleder, Milan; Kmoch, Stanislav

    2011-01-01

    Autosomal-dominant adult-onset neuronal ceroid lipofuscinosis (ANCL) is characterized by accumulation of autofluorescent storage material in neural tissues and neurodegeneration and has an age of onset in the third decade of life or later. The genetic and molecular basis of the disease has remained unknown for many years. We carried out linkage mapping, gene-expression analysis, exome sequencing, and candidate-gene sequencing in affected individuals from 20 families and/or individuals with simplex cases; we identified in five individuals one of two disease-causing mutations, c.346_348delCTC and c.344T>G, in DNAJC5 encoding cysteine-string protein alpha (CSPα). These mutations—causing a deletion, p.Leu116del, and an amino acid exchange, p.Leu115Arg, respectively—are located within the cysteine-string domain of the protein and affect both palmitoylation-dependent sorting and the amount of CSPα in neuronal cells. The resulting depletion of functional CSPα might cause in parallel the presynaptic dysfunction and the progressive neurodegeneration observed in affected individuals and lysosomal accumulation of misfolded and proteolysis-resistant proteins in the form of characteristic ceroid deposits in neurons. Our work represents an important step in the genetic dissection of a genetically heterogeneous group of ANCLs. It also confirms a neuroprotective role for CSPα in humans and demonstrates the need for detailed investigation of CSPα in the neuronal ceroid lipofuscinoses and other neurodegenerative diseases presenting with neuronal protein aggregation. PMID:21820099

  14. MPV17 Mutations Causing Adult-Onset Multisystemic Disorder With Multiple Mitochondrial DNA Deletions

    PubMed Central

    Garone, Caterina; Rubio, Juan Carlos; Calvo, Sarah E.; Naini, Ali; Tanji, Kurenai; DiMauro, Salvatore; Mootha, Vamsi K.; Hirano, Michio

    2014-01-01

    Objective To identify the cause of an adult-onset multisystemic disease with multiple deletions of mitochondrial DNA (mtDNA). Design Case report. Setting University hospitals. Patient A 65-year-old man with axonal sensorimotor peripheral neuropathy, ptosis, ophthalmoparesis, diabetes mellitus, exercise intolerance, steatohepatopathy, depression, parkinsonism, and gastrointestinal dysmotility. Results Skeletal muscle biopsy revealed ragged-red and cytochrome-c oxidase–deficient fibers, and Southern blot analysis showed multiple mtDNA deletions. No deletions were detected in fibroblasts, and the results of quantitative polymerase chain reaction showed that the amount of mtDNA was normal in both muscle and fibroblasts. Exome sequencing using a mitochondrial library revealed compound heterozygous MPV17 mutations (p.LysMet88-89MetLeu and p.Leu143*), a novel cause of mtDNA multiple deletions. Conclusions In addition to causing juvenile-onset disorders with mtDNA depletion, MPV17 mutations can cause adult-onset multisystemic disease with multiple mtDNA deletions. PMID:22964873

  15. A Unique Case of Pica of Adult Onset with Interesting Psychosexual Aspects

    PubMed Central

    Chakraborty, Suddhendu; Sanyal, D.; Bhattacharyya, R.

    2011-01-01

    Pica has been considered as the ingestion of inedible substances or atypical food combinations. Pica has been reported widely in pediatric age group and often found to be co existing with obsessive compulsive or major depressive disorder. Reports of pica in elderly age group are relatively uncommon and rarely does it have an adult onset. In this article we present a case of adult onset pica. A young lady with unusual sensation in her abdomen was found to consume iron nails over years and there was history of dyspareunia since her marriage three months back. On query it was known that the lady is having same sex relationship over years. There unique conglomeration of cultural, psychodynamic and physiological determinants which together is responsible for this unusual habit of this lady. Moreover the onset of the disease at a late age and different psychodynamic issues make the case all the more interesting. Whether the pica is an eating disorder or obsessive compulsive disorder is still controversial. Pica has been mentioned in Diagnostic and Statistical Manual IV TR. The present case report warrants the need to look into this entity more closely with regards to its occurrence and etiology. PMID:22021963

  16. Electrophysiological characterization of adult-onset Niemann-Pick type C disease.

    PubMed

    Iodice, Rosa; Dubbioso, Raffaele; Topa, Antonietta; Ruggiero, Lucia; Pisciotta, Chiara; Esposito, Marcello; Tozza, Stefano; Santoro, Lucio; Manganelli, Fiore

    2015-01-15

    In infantile and juvenile Niemann-Pick type C (NPC) disease electrophysiological studies have shown central (CNS) and peripheral (PNS) nervous system abnormalities. However, an extensive electrophysiological evaluation of CNS and PNS in adult form of NPC is still lacking. The aim of the study is to assess in adult-onset NPC disease the involvement of CNS and PNS by a multimodal electrophysiological approach. Three patients affected by adult form of NPC disease underwent electrophysiological evaluation including nerve conduction study (NCS), magnetic motor (MEPs), visual (VEPs), somatosensory (SSEPs) and brainstem auditory (BAEPs) evoked potentials. NCS, MEPs, VEPs and upper limb SSEPs were normal. Lower limb SSEPs were abnormal in all patients and abnormalities were consistent with a length-dependent process affecting the central somatosensory pathway. BAEPs were abnormal in all patients with both peripheral and central impairment of auditory pathway. Our electrophysiological findings suggest that auditory and lower limb somatosensory pathways are constantly affected in adult-onset form of NPC disease. The involvement of PNS, pyramidal, visual and upper limb somatosensory pathways might occur later during the course of disease. PMID:25537619

  17. Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis

    PubMed Central

    Yang, Yi; Lynch, David R.; Lukas, Thomas; Ahmeti, Kreshnik; Sleiman, Patrick M.A.; Ryan, Eanna; Schadt, Kimberly A.; Newman, Jordan H.; Deng, Han-Xiang; Siddique, Nailah

    2016-01-01

    Objective: To identify the genetic defect for adult-onset primary lateral sclerosis (PLS) in a family with 5 patients. Methods: Whole-exome sequencing was performed to identify the shared genetic variants in 3 affected members in a PLS family with 5 affected individuals. Sanger sequencing was used for validation of the variants and for cosegregation analysis. Mitochondrial activity for both patients and unaffected siblings was measured using a SeaHorse metabolic analyzer. Results: Whole-exome sequencing and subsequent cosegregation analysis demonstrated that compound heterozygous missense variants L695P and I743T in SPG7 were the only mutations cosegregating with the disease in an autosomal recessive fashion in this family. The parents and siblings are genetically heterozygous and clinically unaffected. Functional studies suggested that the PLS-associated SPG7 mutants affect mitochondrial function when glucose is reduced. Conclusions: Compound heterozygote mutations in SPG7 are associated with adult-onset PLS, extending the spectrum of SPG7-linked neurologic diseases. Patients with the PLS phenotype should have genetic testing for paraplegin, especially when the condition is familial. PMID:27123479

  18. Adult-Onset Presentations of Genetic Immunodeficiencies: Genes Can Throw Slow Curves

    PubMed Central

    Nelson, Katharine S.; Lewis, David B.

    2016-01-01

    Purpose of Review The molecular and genetic mechanisms behind adult presentations of primary immunodeficiency diseases are examined, with particular emphasis on cases where this was heralded by severe, recurrent or opportunistic infection. Recent Findings A detailed analysis over the last two decades of the relationship between genotype and clinical phenotype for a number of genetic immunodeficiencies has revealed multiple mechanisms that can account for the delayed presentation of genetic disorders that typically present in childhood, including hypomorphic gene mutations and X-linked gene mutations with age-related skewing in random X-chromosome inactivation. Adult-onset presentations of chronic granulomatous disease, X-linked agammaglobulinemia, interleukin-12/T helper 1/interferon-gamma and interleukin-23/T helper 17/interleukin-17 pathway defects, and X-linked lymphoproliferative disorder are used to illustrate these mechanisms. Finally, certain genetic types of common variable immunodeficiency are used to illustrate that inherited null mutations can take decades to manifest immunologically. Summary Both genetic mechanisms and environmental factors can account for adult-onset infectious and non-infectious complications as manifestations of disorders that typically present in childhood. This emphasizes the potential complexity in the relationship between genotype and phenotype with natural human mutations. PMID:20581672

  19. Prevalence of adult-onset multifactorial disease among offspring of atomic bomb survivors.

    PubMed

    Fujiwara, S; Suyama, A; Cologne, J B; Akahoshi, M; Yamada, M; Suzuki, G; Koyama, K; Takahashi, N; Kasagi, E; Grant, E J; Lagarde, E; Hsu, W L; Furukawa, K; Ohishi, W; Tatsukawa, Y; Neriishi, K; Takahashi, I; Ashizawa, K; Hida, A; Imaizumi, M; Nagano, J; Cullings, H M; Katayama, H; Ross, N P; Kodama, K; Shore, R E

    2008-10-01

    The first study to examine whether parental radiation exposure leads to increased heritable risk of common adult-onset multifactorial diseases (i.e., hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, and stroke) was conducted among 11,951 participants in the clinical examination program out of a potential of 24,673 mail survey subjects who were offspring of survivors born from May 1946 through December 1984. Logistic regression analyses demonstrated no evidence of an association between the prevalence of multifactorial diseases in the offspring and parental radiation exposure, after adjusting for age, city, gender and various risk factors. The odds ratio (OR) for a paternal dose of 1 Gy was 0.91 [95% confidence interval (CI) 0.81-1.01, P = 0.08], and that for a maternal dose of 1 Gy was 0.98 (95% CI 0.86-1.10, P = 0.71). There was no apparent effect of parental age at exposure or of elapsed time between parental exposure and birth, but male offspring had a low odds ratio (OR = 0.76 at 1 Gy) for paternal exposure, but cautious interpretation is needed for this finding. The clinical assessment of nearly 12,000 offspring of A-bomb survivors who have reached a median age of about 50 years provided no evidence for an increased prevalence of adult-onset multifactorial diseases in relation to parental radiation exposure. PMID:19024652

  20. Chinese new immigrant mothers' perception about adult-onset non-communicable diseases prevention during childhood.

    PubMed

    Wang, Linda Dong Ling; Lam, Wendy Wing Tak; Wu, Joseph Tsz Kei; Fielding, Richard

    2015-12-01

    Many non-communicable diseases (NCDs) are largely preventable via behaviour change and healthy lifestyle, which may be best established during childhood. This study sought insights into Chinese new immigrant mothers' perceptions about adult-onset NCDs prevention during childhood. Twenty-three semi-structured interviews were carried out with new immigrant mothers from mainland China who had at least one child aged 14 years or younger living in Hong Kong. Interviews were audio taped, transcribed and analysed using a Grounded Theory approach. The present study identified three major themes: perceived causes of adult NCDs, beliefs about NCDs prevention and everyday health information practices. Unhealthy lifestyle, contaminated food and environment pollution were perceived as the primary causes of adult NCDs. Less than half of the participants recognized that parents had responsibility for helping children establish healthy behaviours from an early age to prevent diseases in later life. Most participants expressed helplessness about chronic diseases prevention due to lack of knowledge of prevention, being perceived as beyond individual control. Many participants experienced barriers to seeking health information, the most common sources of health information being interpersonal conversation and television. Participants' everyday information practice was passive and generally lacked awareness regarding early prevention of adult-onset NCDs. Updated understanding of this issue has notable implications for future health promotion interventions. PMID:24842077

  1. Distinguishing adult-onset asthma from COPD: a review and a new approach

    PubMed Central

    Abramson, Michael J; Perret, Jennifer L; Dharmage, Shyamali C; McDonald, Vanessa M; McDonald, Christine F

    2014-01-01

    Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene–environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and

  2. Case report: An adult-onset type II citrin deficiency patient in the emergency department

    PubMed Central

    TANG, LUJIA; CHEN, LIANG; WANG, HAIRONG; DAI, LIHUA; PAN, SHUMING

    2016-01-01

    Mutations in the solute carrier family 25 (SLC25A13) gene may result in neonatal intrahepatic cholestasis caused by citrin deficiency and/or adult-onset type II citrullinemia. These conditions are inherited in an autosomal recessive manner. The current case report describes a 43-year-old man who presented with sudden delirium and upper limb weakness. Upon admission, the patient was fully conscious and alert but later lost consciousness subsequent to a sudden convulsive seizure. Hyperammonemia was detected and analysis of the SLC25A13 gene identified an 851del4 mutation. Thus, the possibility of genetic disease should be considered as a potential cause of the symptoms of patients with altered states of consciousness, such as delirium and loss of consciousness, in cases where the cause of the disturbance is unknown. PMID:27347070

  3. Adult onset Still's disease accompanied by acute respiratory distress syndrome: A case report

    PubMed Central

    Xi, Xiao-Tu; Wang, Mao-Jie; Huang, Run-Yue; Ding, Bang-Han

    2016-01-01

    Adult onset Still's disease (AOSD) is a systemic inflammatory disorder characterized by rash, leukocytosis, fever and arthralgia/arthritis. The most common pulmonary manifestations associated with AOSD are pulmonary infiltrates and pleural effusion. The present study describes a 40-year-old male with AOSD who developed fever, sore throat and shortness of breath. Difficulty breathing promptly developed, and the patient was diagnosed with acute respiratory distress syndrome (ARDS). The patient did not respond to antibiotics, including imipenem, vancomycin, fluconazole, moxifloxacin, penicillin, doxycycline and meropenem, but was sensitive to glucocorticoid treatment, including methylprednisolone sodium succinate. ARDS accompanied by AOSD has been rarely reported in the literature. In conclusion, in a patient with ARDS who does not respond to antibiotic treatment, the involvement of AOSD should be considered. PMID:27588099

  4. Hidden in plain sight: macrophage activation syndrome complicating Adult Onset Still's Disease.

    PubMed

    Benitez, Lourdes; Vila, Salvador; Mellado, Robert Hunter

    2010-01-01

    Hemophagocytic Lymphystiocytosis is a rare and fatal complication of rheumatic diseases, particularly Adult Onset Still's Disease (AOSD). It may be precipitated with immunosuppressive drugs and with viral and bacterial infections. A diagnosis depends on a high index of suspicion associated to certain clinical manifestations (fever, rash, Splemomegaly, any cytology blood dyscrasia, hipertrigliceridemia, hiperfibrinogenemia, and others), as well as pathologic evidence of hemophagocitosis from bone marrow biopsy or tissue samples of affected organs. Therapy consists of high dose corticosteroids and immunosuppressive drugs. We present a 42 year old woman with AOSD in remission who developed HLH in spite of receiving therapy with high dose steroids and immunosuppressive drugs. She had 2 negative bone marrow aspirates. Evidence of Hemophagocytosis was detected in both bone marrow biopsies. Timely evaluation and recognition of the signs and symptoms of HLH is crucial for the prompt management and a decrease in the mortality associated with this disease. PMID:23875527

  5. A mouse model of adult-onset anaemia due to erythropoietin deficiency.

    PubMed

    Yamazaki, Shun; Souma, Tomokazu; Hirano, Ikuo; Pan, Xiaoqing; Minegishi, Naoko; Suzuki, Norio; Yamamoto, Masayuki

    2013-01-01

    Erythropoietin regulates erythropoiesis in a hypoxia-inducible manner. Here we generate inherited super-anaemic mice (ISAM) as a mouse model of adult-onset anaemia caused by erythropoietin deficiency. ISAM express erythropoietin in the liver but lack erythropoietin production in the kidney. Around weaning age, when the major erythropoietin-producing organ switches from the liver to the kidney, ISAM develop anaemia due to erythropoietin deficiency, which is curable by administration of recombinant erythropoietin. In ISAM severe chronic anaemia enhances transgenic green fluorescent protein and Cre expression driven by the complete erythropoietin-gene regulatory regions, which facilitates efficient labelling of renal erythropoietin-producing cells. We show that the majority of cortical and outer medullary fibroblasts have the innate potential to produce erythropoietin, and also reveal a new set of erythropoietin target genes. ISAM are a useful tool for the evaluation of erythropoiesis-stimulating agents and to trace the dynamics of erythropoietin-producing cells. PMID:23727690

  6. Predictive Medicine: Recombinant DNA Technology and Adult-Onset Genetic Disorders

    PubMed Central

    Hayden, Michael

    1988-01-01

    Genetic factors are of great importance in common adult-onset disorders such as atherosclerosis, cancer, and neuro-degenerative diseases. Advances in DNA technology now allow identification of persons at high-risk of developing some of these diseases. This advance is leading to predictive medicine. In some genetic disorders, such as those leading to atherosclerosis and cancer, identification of high-risk individuals allows intervention which alters the natural history of the disorder. In other diseases, for which there is no treatment, such as Huntington's disease, the application of this technology provides information that relieves uncertainty and may affect quality of life, but does not alter the course of the illness. General implementation of predictive testing programs awaits the results of pilot projects, which will demonstrate the needs, appropriate levels of support, and guidelines for delivery of such testing. PMID:21253100

  7. Blepharospasm-oromandibular dystonia syndrome (Brueghel's syndrome). A variant of adult-onset torsion dystonia?

    PubMed Central

    Marsden, C D

    1976-01-01

    Thirty-nine patients with the idiopathic blepharospasm-oromandibular dystonia syndrome are described. All presented in adult life, usually in the sixth decade; women were more commonly affected than men. Thirteen had blepharospasm alone, nine had oromandibular dystonia alone, and 17 had both. Torticollis or dystonic writer's camp preceded the syndrome in two patients. Eight other patients developed toritocollis, dystonic posturing of the arms, or involvement of respiratory muscles. No cause or hereditary basis for the illness were discovered. The evidence to indicate that this syndrome is due to an abnormality of extrapyramidal function, and that it is another example of adult-onset focal dystonia akin to spasmodic torticollis and dystonic writer's cramp, is discussed. Images PMID:1011031

  8. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders

    PubMed Central

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary “myopathic” changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions. PMID:26999347

  9. A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q

    SciTech Connect

    Morissette, J.; Plante, M.; Raymond, V.

    1995-06-01

    Primary open-angle glaucoma (POAG), which causes progressive loss of the visual fields, was subdivided into two groups according to age at onset: (1) chronic open-angle glaucoma (COAG) diagnosed after 40 years and (2) juvenile open-angle glaucoma (JOAG) diagnosed between 3 years of age and early adulthood. A JOAG gene (GLC1A) was recently mapped to chromosome 1q. We studied 142 members of a huge multigenerational French Canadian family affected with autosomal dominant POAG. Either JOAG or COAG was diagnosed with ocular hypertension (OHT), which may lead to POAG. To localize a common disease gene that might be responsible for both glaucoma subsets, we performed linkage analysis considering JOAG and COAG under the same phenotypic category. JOAG/COAG was tightly linked to seven microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 was obtained with AF-M278ye5. To refine the disease locus, we exploited a recombination mapping strategy based on a unique founder effect. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or OHT, but it did not occur in unaffected spouses and in normal family members >35 years of age, except for three obligatory carriers. Key combination events confined the disease region within a 9-cM interval between loci D1S445 and D1S416/D1S480. These observations demonstrate that the GLC1A gene is responsible for both adult-onset and juvenile glaucomas and suggest that the JOAG and COAG categories within this family may be part of a clinical continuum artificially divided at age 40 years. 49 refs., 4 figs., 2 tabs.

  10. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

    PubMed Central

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-01-01

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

  11. The distinction between juvenile and adult-onset primary open-angle glaucoma

    SciTech Connect

    Wiggs, J.L.; Haines, J.L.; Damji, K.F.

    1996-01-01

    Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light of the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.

  12. Adult onset sinonasal rhabdomyosarcoma - a rare case report with cytohistological features.

    PubMed

    Sood, N; Sehrawat, N

    2016-08-01

    Rhabdomyosarcoma (RMS) is a fast growing, malignant tumour arising from immature mesenchymal cells, committed to skeletal muscle differentiation. It is more often seen in the paediatric population and constitutes less than 1% of all malignancies and less than 3% of all soft tissue tumours. RMS of the paranasal sinuses constitutes 10-15% of adult head and neck RMS, ethmoidal and maxillary sinuses being the most common. We report a 56-year-oldman presenting with left nasal obstruction, epistaxis on and off and left cheek swelling. Nasal endoscopy revealed a reddish friable mass, bleeding on touch, in the left nasal cavity. CECT scan showed a heterogeneous growth in the left maxillary sinus eroding the medial orbital wall and lateral nasal wall. FNAC of the left cheek swelling yielded highly cellular smears showing predominantly singly scattered round to ovoid neoplastic cells with scanty cytoplasm and indistinct nucleoli. Few of the cells had eccentric nuclei with moderate amount of eosinophilic cytoplasm. Attempted pseudorossette formation was seen. An impression of round cell tumour was given. A diagnosis of an adult onset sinonasal rhabdomyosarcoma was made on histopathological examination of the nasal biopsy, supported by immunohistochemistry (IHC) showing strong myogenin positivity, focal positivity for PAX8 and negativity for CK, LCA, S-100 and CD99. Parameningeal RMS is rare in adults especially the elderly. However, it needs to be considered whenever a poorly-differentiated neoplasm is seen in this age and IHC is a useful aid. PMID:27568676

  13. Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

    PubMed Central

    Cardin, Velia

    2016-01-01

    Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

  14. Multimodal Image Analysis in Acquired Vitelliform Lesions and Adult-Onset Foveomacular Vitelliform Dystrophy

    PubMed Central

    Rocha Bastos, Ricardo; Ferreira, Carla Sofia; Brandão, Elisete; Falcão-Reis, Fernando; Carneiro, Ângela M.

    2016-01-01

    Purpose. To characterize vitelliform lesions (VLs) in adult-onset foveomacular vitelliform dystrophy (AOFVD) and acquired vitelliform (AVL) patients using multimodal image analysis. Methods. Retrospective study of twenty-eight eyes from nineteen patients diagnosed with AVL or AOFVD. They were evaluated by color fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA), and spectral-domain optical coherence tomography (SD-OCT). Results. Bilateral VLs were associated with AOFVD (p = 0.013). Regular and centered VLs were associated with AOFVD (p = 0.004 and p = 0.016), whereas irregular and noncentered lesions were more frequent in AVL patients. Visual acuity, greatest linear dimension (GLD), lesion height (LH), and pseudohypopyon were similar between groups. Whereas median LH and GLD in AVL group diminished significantly during follow-up (p = 0.009 and p = 0.001), AOFVD lesions tended to become larger and thicker. Conclusions. When consulting a patient presenting a VL with unknown age of onset, familial history, or previous retinal diseases, some aspects of multimodal imaging assessment may lead the ophthalmologist to a correct diagnosis. PMID:27190637

  15. Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala

    PubMed Central

    Montero-Pedrazuela, Ana; Fernández-Lamo, Iván; Alieva, María; Pereda-Pérez, Inmaculada; Venero, César; Guadaño-Ferraz, Ana

    2011-01-01

    Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment. PMID:22039511

  16. A search for the primary abnormality in adult-onset type II citrullinemia

    SciTech Connect

    Kobayashi, Keiko; Shaheen, Nazma; Saheki, Takeyori ); Kumashiro, Ryukichi; Tanikawa, Kyuichi ); O'Brien, W.E.; Beaudet, A.L. )

    1993-11-01

    Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, the authors show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. The authors also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. 29 refs., 1 fig., 3 tabs.

  17. Multimodal Image Analysis in Acquired Vitelliform Lesions and Adult-Onset Foveomacular Vitelliform Dystrophy.

    PubMed

    Rocha Bastos, Ricardo; Ferreira, Carla Sofia; Brandão, Elisete; Falcão-Reis, Fernando; Carneiro, Ângela M

    2016-01-01

    Purpose. To characterize vitelliform lesions (VLs) in adult-onset foveomacular vitelliform dystrophy (AOFVD) and acquired vitelliform (AVL) patients using multimodal image analysis. Methods. Retrospective study of twenty-eight eyes from nineteen patients diagnosed with AVL or AOFVD. They were evaluated by color fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA), and spectral-domain optical coherence tomography (SD-OCT). Results. Bilateral VLs were associated with AOFVD (p = 0.013). Regular and centered VLs were associated with AOFVD (p = 0.004 and p = 0.016), whereas irregular and noncentered lesions were more frequent in AVL patients. Visual acuity, greatest linear dimension (GLD), lesion height (LH), and pseudohypopyon were similar between groups. Whereas median LH and GLD in AVL group diminished significantly during follow-up (p = 0.009 and p = 0.001), AOFVD lesions tended to become larger and thicker. Conclusions. When consulting a patient presenting a VL with unknown age of onset, familial history, or previous retinal diseases, some aspects of multimodal imaging assessment may lead the ophthalmologist to a correct diagnosis. PMID:27190637

  18. Intermittent rhabdomyolysis with adult onset associated with a mutation in the ACADVL gene.

    PubMed

    Antunes, Ana Patrícia; Nogueira, Célia; Rocha, Hugo; Vilarinho, Laura; Evangelista, Teresinha

    2013-12-01

    Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD) is an autosomal recessive disease. Most common phenotypes occur in the neonatal period or in childhood with cardiomyopathy, hepatomegaly, and hypoketogenic hypoglycemia. Juvenile/adult-onset is characterized by exercise intolerance and recurrent rhabdomyolysis triggered by prolonged exercise or fasting. This article reports a patient with the homozygous mutation c.1097G>A (p.R366H) in the ACADVL gene. In Portugal, VLCAD deficiency became part of the neonatal screening plan in 2004, and as of 2012, 8 early-onset cases have been diagnosed, giving an incidence rate of 1:97.238 per 737.902 newborns. This patient was diagnosed outside of the neonatal screening plan. Beta-oxidation defects pose a diagnostic challenge because of their transient clinical and laboratorial manifestations and the absence of morphological changes in muscle biopsy further complicate matters, especially in the late-onset forms of the disease. The adult phenotype of VLCAD deficiency is highlighted, emphasizing the need for a high suspicion index and the value of tandem mass spectrometry for the diagnosis. PMID:24263034

  19. A search for the primary abnormality in adult-onset type II citrullinemia.

    PubMed

    Kobayashi, K; Shaheen, N; Kumashiro, R; Tanikawa, K; O'Brien, W E; Beaudet, A L; Saheki, T

    1993-11-01

    Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, we show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. We also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. PMID:8105687

  20. [A case of adult-onset type II citrullinemia (CTLN2) triggered by an overseas travel].

    PubMed

    Yamasaki, Masayoshi; Shimada, Takuya; Hamaoka, Shima; Shibata, Masunari; Naito, Yutaka

    2014-01-01

    A 43-year-old male presented with abnormal behavior and consciousness disturbance on the day after traveling abroad and was admitted to our hospital. Laboratory tests showed hyperammonemia and hypercitrullinemia. The electro-encephalogram showed frontal dominant bilateral slow δ burst. He had a peculiar taste for nuts. But he didn't take nuts during the overseas travel for 3 days. The family history revealed that his younger brother died of a status epilepticus of unknown cause at the age of 29. These findings were compatible with hepatic encephalopathy due to adult-onset type II citrullinemia (CTLN2). Gene analysis provided a definite diagnosis of CTLN2. Diet and drug therapy have improved his condition. He is due to have liver transplantation which is the only established radical treatment for CTLN2 if his condition becomes worse. The present case shows that cessation of the habitual intake of nuts only for 3 days could lead to onset of CTLN2. PMID:25283831

  1. Multiple sclerosis and risk of young-adult-onset Hodgkin lymphoma

    PubMed Central

    Hajiebrahimi, Mohammadhossein; Burkill, Sarah; Hillert, Jan; Olsson, Tomas; Bahmanyar, Shahram

    2016-01-01

    Objective: To determine whether there is an association between multiple sclerosis (MS) and young-adult-onset Hodgkin lymphoma (YAHL) as this will signal etiologic similarities relevant both to inherited characteristics and environmental exposures in childhood. Methods: Swedish general population registers identified a cohort of 29,617 with an MS diagnosis between 1968 and 2012, matched with a cohort of 296,164 without MS. Cox regression was used to assess the association of MS with subsequent YAHL (defined as onset between ages 15 and 39 years; n = 20), with adjustment, for age/period, sex, county of residence, and level of education. Results: The adjusted hazard ratio (and 95% confidence interval) for the association of MS with YAHL is 3.30 (1.01–10.73), resulting from 4 and 16 events in the MS and non-MS cohorts, respectively. All 4 of the YAHL diagnoses in MS occurred in women, and the association of MS with YAHL has a hazard ratio of 4.04 (1.17–13.94) among women. There was no notable association of MS with older-onset Hodgkin lymphoma. Conclusion: There may be common risks for YAHL and MS, consistent with an etiologic role in MS for early-life exposures, such as to infectious agents. PMID:27144218

  2. Spacetimes containing slowly evolving horizons

    SciTech Connect

    Kavanagh, William; Booth, Ivan

    2006-08-15

    Slowly evolving horizons are trapping horizons that are ''almost'' isolated horizons. This paper reviews their definition and discusses several spacetimes containing such structures. These include certain Vaidya and Tolman-Bondi solutions as well as (perturbatively) tidally distorted black holes. Taking into account the mass scales and orders of magnitude that arise in these calculations, we conjecture that slowly evolving horizons are the norm rather than the exception in astrophysical processes that involve stellar-scale black holes.

  3. Steatogenesis in adult-onset type II citrullinemia is associated with down-regulation of PPARα.

    PubMed

    Komatsu, Michiharu; Kimura, Takefumi; Yazaki, Masahide; Tanaka, Naoki; Yang, Yang; Nakajima, Takero; Horiuchi, Akira; Fang, Zhong-Ze; Joshita, Satoru; Matsumoto, Akihiro; Umemura, Takeji; Tanaka, Eiji; Gonzalez, Frank J; Ikeda, Shu-Ichi; Aoyama, Toshifumi

    2015-03-01

    SLC25A13 (citrin or aspartate-glutamate carrier 2) is located in the mitochondrial membrane in the liver and its genetic deficiency causes adult-onset type II citrullinemia (CTLN2). CTLN2 is one of the urea cycle disorders characterized by sudden-onset hyperammonemia due to reduced argininosuccinate synthase activity. This disorder is frequently accompanied with hepatosteatosis in the absence of obesity and ethanol consumption. However, the precise mechanism of steatogenesis remains unclear. The expression of genes associated with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from 16 CTLN2 patients and compared with 7 healthy individuals. Although expression of hepatic genes associated with lipogenesis and TG hydrolysis was not changed, the mRNAs encoding enzymes/proteins involved in FA oxidation (carnitine palmitoyl-CoA transferase 1α, medium- and very-long-chain acyl-CoA dehydrogenases, and acyl-CoA oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1), were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial β-oxidation activity. Consistent with these findings, the expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of hepatic lipid metabolism, was significantly down-regulated. Hepatic PPARα expression was inversely correlated with severity of steatosis and circulating ammonia and citrulline levels. Additionally, phosphorylation of c-Jun-N-terminal kinase was enhanced in CTLN2 livers, which was likely associated with lower hepatic PPARα. Collectively, down-regulation of PPARα is associated with steatogenesis in CTLN2 patients. These findings provide a novel link between urea cycle disorder, lipid metabolism, and PPARα. PMID:25533124

  4. Prevalence of reticular pseudodrusen in newly presenting adult onset foveomacular vitelliform dystrophy.

    PubMed

    Wilde, C; Lakshmanan, A; Patel, M; Morales, M U; Dhar-Munshi, S; Amoaku, W M K

    2016-06-01

    PurposeTo report the association and prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting adult onset foveomacular vitelliform dystrophy (AFVD). To compare the strength of association with other pathologies resulting from dysfunction of the choroid-Bruch's membrane-retinal pigment epithelium (RPE) complex, including eyes with geographic atrophy (GA) and angioid streaks.MethodsRetrospective single-centre review of all consecutive newly presenting AFVD. Multimodal imaging with spectral domain optical coherence tomography, fundus photographs, red-free/blue light images, and fundus fluorescein angiograms were graded for the presence of RPD. For comparison, all consecutive newly presenting cases of GA and eyes with angioid streaks were studied.ResultsFifteen (15) patients were identified with AFVD (mean age of 77.3 years; 73.3% female). Mean age of patients with AFVD and RPD was 80.5 years (SD 3.7), whereas that of patients with AFVD without RPD was 75.1 years (SD 7.0). This age difference did not reach statistical significance, P=0.1. Six (40%) had identifiable RPD; being a bilateral finding in 100% of patients. No males with AFVD and RPD were identified. A total of 92 eyes presented with GA. Twenty-three (23) of these (25.0%) had RPD. Twelve (12) patients presented with identifiable angioid streaks, with 4 (36.4%) having RPD.ConclusionRPD are a frequent finding in eyes with newly presenting AFVD; not being restricted to AMD, but a finding common among diseases where pathophysiological mechanisms involve damage to Bruch's membrane and the RPE, whether genetic or degenerative. Our study supports the concept that they occur with high but variable frequencies in eyes with various pathologies. PMID:27034200

  5. [Adult-onset Hartnup disease presenting with neuropsychiatric symptoms but without skin lesions].

    PubMed

    Mori, E; Yamadori, A; Tsutsumi, A; Kyotani, Y

    1989-06-01

    Hartnup disease is an inborn abnormality of renal and intestinal transport involving the neutral amino acids. Intermittent pellagra-like rash, attacks of cerebellar ataxia and psychiatric disturbance are characteristic symptoms of this disease. We described here a patient with adult-onset Hartnup disease who presented unique neuropsychiatric symptoms but no dermatologic symptoms, and reported features of amino acids transport in this patient and his family. The patient, a man aged 37 years, was referred to us because of lasting daytime bruxism. He is the second child of healthy parents who are first cousin; his elder brother who has been mentally retarded became bed-ridden and died at 32 years of age. His younger brother is completely healthy. Although the patient's development in infancy has been slightly retarded, he completed compulsory 9-year education. At 29 years of age, he experienced episodes of diplopia, ataxic gait and insomnia, and at 33 years of age, of transient stupor. There had been no history of photosensitivity or dermatitis. On neurological examination, there were trunkal ataxia, increased muscular tone and decreased mental activity besides bruxism. These symptoms remained unchanged despite of several medications including trihexyphenidyl, diazepam, halloperidol, tiapride and sulpiride. Two months later, the patient became stuporous; bruxism and hypertonicity became exaggerated. Myerson's sign, sucking reflex and grasp reflex in both hand appeared. There was no dermal lesion. A cranial computed tomography revealed a small calcification in the right frontal subcortical region and a single photon emission tomography indicated possible bifrontal hypoperfusion. Electroencephalograms demonstrated non-specific slowing. Somatosensory evoked potentials and nerve conduction velocities were normal. There were constant indicanuria and amino-aciduria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2582682

  6. Astrocyte Leptin Receptor (ObR) and Leptin Transport in Adult-Onset Obese Mice

    PubMed Central

    Pan, Weihong; Hsuchou, Hung; He, Yi; Sakharkar, Amul; Cain, Courtney; Yu, Chuanhui; Kastin, Abba J.

    2008-01-01

    The agouti viable yellow (Avy) spontaneous mutation generates an unusual mouse phenotype of agouti-colored coat and adult-onset obesity with metabolic syndrome. Persistent production of agouti signaling protein in Avy mice antagonizes melanocortin receptors in the hypothalamus. To determine how this disruption of neuroendocrine circuits affects leptin transport across the blood-brain barrier (BBB), we measured leptin influx in Avy and B6 control mice after the development of obesity, hyperleptinemia, and increased adiposity. After iv bolus injection, 125I-leptin crossed the BBB significantly faster in young (2 month old) B6 mice than in young Avy mice or in older (8 month old) mice of either strain. This difference was not observed by in situ brain perfusion studies, indicating the cause being circulating factors, such as elevated leptin levels or soluble receptors. Thus, Avy mice showed peripheral leptin resistance. ObRa, the main transporting receptor for leptin at the BBB, showed no change in mRNA expression in the cerebral microvessels between the age-matched (2 month old) Avy and B6 mice. Higher ObRb mRNA was seen in the Avy microvasculature with unknown significance. Immunofluorescent staining unexpectedly revealed that many of the ObR(+) cells were astrocytes and that the Avy mice showed significantly more ObR(+) astrocytes in the hypothalamus than the B6 mice. Although leptin permeation from the circulation was slower in the Avy mice, the increased ObR expression in astrocytes and increased ObRb mRNA in microvessels suggest the possibility of heightened central nervous system sensitivity to circulating leptin. PMID:18292187

  7. Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series

    PubMed Central

    Jaunmuktane, Zane; Sheerin, Una-Marie; Phadke, Rahul; Brandner, Sebastian; Milonas, Ionnis; Dean, Andrew; Bajaj, Nin; McNicholas, Nuala; Costello, Daniel; Cronin, Simon; McGuigan, Chris; Rossor, Martin; Fox, Nick; Murphy, Elaine; Chataway, Jeremy; Houlden, Henry

    2016-01-01

    Background Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene. Methods In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause. Results Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations. Conclusion We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia. PMID:25935893

  8. Exclusion of one pedigree affected by adult onset primary open angle glaucoma from linkage to the juvenile glaucoma locus on chromosome 1q21-q31.

    PubMed Central

    Avramopoulos, D; Kitsos, G; Economou-Petersen, E; Grigoriadou, M; Vassilopoulos, D; Papageorgiou, C; Psilas, K; Petersen, M B

    1996-01-01

    A locus for autosomal dominant juvenile onset primary open angle glaucoma (POAG) was recently assigned to chromosome region 1q21-q31. In the present study, a large Greek family with autosomal dominant adult onset POAG was investigated using microsatellite markers. Exclusion of linkage of the adult onset POAG gene to the region D1S194-D1S191 was obtained in this pedigree. Therefore, the data provide evidence that juvenile and adult onset POAG are genetically distinct disease entities. PMID:9004141

  9. An increased incidence of Hodgkin's lymphoma in patients with adult-onset sarcoma

    PubMed Central

    2012-01-01

    Background Sarcomas are rare, often fatal malignancies of connective tissues that can occur in genetic predisposition syndromes or result from carcinogen exposure. Hodgkin's lymphoma (HL) is not known to contribute to any recognised familial cancer syndrome comprising sarcomas, but is known to be associated with a variety of second cancers, including sarcomas. This study describes the prevalence of HL in families affected by sarcoma. Methods The International Sarcoma Kindred Study (ISKS) is a prospective cohort of 561 families ascertained via a proband with adult-onset sarcoma. Cancer-specific standardised incidence ratios (SIR) for multiple primary malignancies in probands were estimated. Clinical characteristics of individuals reporting both sarcoma and HL were described. Standardised incidence ratios for the occurrence of cancer in ISKS families were also estimated. Results Multiple primary cancers were reported in 16% of probands, significantly higher than in the general population. The risk of HL in probands was increased 15.8-fold (95%CI 7.9-31.6) and increased risks were also seen for breast cancer (SIR 2.9, 95%CI 1.9-4.4) and thyroid cancer (SIR 8.4, 95%CI 4.2-16.8). In 8 probands with both HL and sarcoma, the diagnosis of HL preceded that of sarcoma in 7 cases, and occurred synchronously in one case. Only 3 cases of sarcoma occurred in or close to prior radiotherapy fields. The overall incidence of HL in the ISKS cohort was not significantly increased by comparison with age- and gender-specific population estimates (SIR 1.63, 95%CI 1.05-2.43), suggesting that the association between HL and sarcomas did not extend to other family members. The age of onset of non-sarcoma, non-HL cancers in families affected by both HL and sarcoma was younger than the general population (56.2 y vs 65.6 y, P < 0.0001). Conclusions The basis for the association between HL and sarcomas may include the carcinogenic effects of therapy combined with excellent survival rates for HL

  10. Slowly rotating homogeneous masses revisited

    NASA Astrophysics Data System (ADS)

    Reina, Borja

    2016-02-01

    Hartle's model for slowly rotating stars has been extensively used to compute equilibrium configurations of slowly rotating stars to second order in perturbation theory in general relativity, given a barotropic equation of state. A recent study based on the modern theory of perturbed matchings concludes that the functions in the (first and second order) perturbation tensors can always be taken as continuous at the surface of the star, except for the second-order function m0. This function presents a jump at the surface of the star proportional to the discontinuity of the energy density there. This concerns only a particular outcome of the model: the change in mass δM. In this paper, the amended change in mass is calculated for the case of constant density stars.

  11. Slowly braked, rotating neutron stars

    NASA Technical Reports Server (NTRS)

    Sato, H.

    1975-01-01

    A slowly braked, rotating neutron star is believed to be a star which rapidly rotates, has no nebula, is nonpulsing, and has a long initial braking time of ten thousand to a million years because of a low magnetic field. Such an object might be observable as an extended weak source of infrared or radio wave radiation due to the scattering of low-frequency strong-wave photons by accelerated electrons. If these objects exist abundantly in the Galaxy, they would act as sources of relatively low-energy cosmic rays. Pulsars (rapidly braked neutron stars) are shown to have difficulties in providing an adequate amount of cosmic-ray matter, making these new sources seem necessary. The possibility that the acceleration mechanism around a slowly braked star may be not a direct acceleration by the strong wave but an acceleration due to plasma turbulence excited by the strong wave is briefly explored. It is shown that white dwarfs may also be slowly braked stars with braking times longer than 3.15 million years.

  12. Obesity-related abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D.

    PubMed

    Nguyen, K Hoa; Ande, Sudharsana R; Mishra, Suresh

    2016-01-29

    The incidence of adult-onset T1D in low-risk non-HLA type has increased several folds, whereas the contemporaneous incidence in high-risk HLA-type remains stable. Various factors behind this selective increase in T1D in young adults remain unclear. Obesity and its associated abnormalities appear to be an important determinant; however, the underlying mechanism involved is not understood. Recently, we have developed two novel transgenic obese mice models, Mito-Ob and m-Mito-Ob, by expressing a pleiotropic protein prohibitin (PHB) and a phospho mutant form of PHB (Y114F-PHB or m-PHB) from the aP2 gene promoter, respectively. Both mice models develop obesity in a sex-neutral manner, independent of diet; but obesity associated chronic low-grade inflammation and insulin resistance in a male sex-specific manner. Interestingly, on a high fat diet (HFD) only male m-Mito-Ob mice displayed marked mononuclear cell infiltration in pancreas and developed insulitis that mimic adult-onset T1D. Male Mito-Ob mice that share the metabolic phenotype of male m-Mito-Ob mice, and female m-Mito-Ob that harbor m-PHB similar to male m-Mito-Ob mice, did not develop insulitis. Thus, insulitis development in male m-Mito-Ob in response to HFD requires both, obesity-related abnormalities and m-PHB. Collectively, this data provides a proof-of-concept that obesity-associated abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D and reveals PHB as a potential susceptibility gene for T1D. PMID:26766792

  13. Piriform sinus carcinoma with a paraneoplastic syndrome misdiagnosed as adult onset Still’s disease: a case report

    PubMed Central

    Yang, Liu; Li, Wen; Du, Jintao

    2015-01-01

    Paraneoplastic syndromes (PS) occur less commonly in association with otolaryngologic neoplasms than other carcinomas such as those of lung or breast. Piriform sinus carcinoma with PS is extremely rare. We here report a case of piriform sinus carcinoma accompanied by PS that was initially misdiagnosed as adult onset Still’s disease and describe our diagnosis and treatment. One lesson we have drawn from the experience of this misdiagnosis is that PS symptoms may manifest before the primary tumor is evident and complicate the diagnostic process. PMID:26770614

  14. A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)

    SciTech Connect

    Giorgio, E.; Robyr, D.; Spielmann, M.; Ferrero, E.; Di Gregorio, E.; Imperiale, D.; Vaula, G.; Stamoulis, G.; Santoni, F.; Atzori, C.; Gasparini, L.; Ferrera, D.; Canale, C.; Guipponi, M.; Pennacchio, L. A.; Antonarakis, S. E.; Brussino, A.; Brusco, A.

    2015-02-20

    Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (~660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in a postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. The deletion eliminates a genome topological domain boundary, allowing normally forbidden interactions between at least three forebrain-directed enhancers and the LMNB1 promoter, in line with the observed mainly cerebral localization of lamin B1 overexpression and myelin degeneration. Finally, this second route to LMNB1 overexpression and ADLD is a new example of the relevance of regulatory landscape modifications in determining Mendelian phenotypes.

  15. A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)

    DOE PAGESBeta

    Giorgio, E.; Robyr, D.; Spielmann, M.; Ferrero, E.; Di Gregorio, E.; Imperiale, D.; Vaula, G.; Stamoulis, G.; Santoni, F.; Atzori, C.; et al

    2015-02-20

    Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (~660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in amore » postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. The deletion eliminates a genome topological domain boundary, allowing normally forbidden interactions between at least three forebrain-directed enhancers and the LMNB1 promoter, in line with the observed mainly cerebral localization of lamin B1 overexpression and myelin degeneration. Finally, this second route to LMNB1 overexpression and ADLD is a new example of the relevance of regulatory landscape modifications in determining Mendelian phenotypes.« less

  16. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43.

    PubMed

    Arnold, Eveline S; Ling, Shuo-Chien; Huelga, Stephanie C; Lagier-Tourenne, Clotilde; Polymenidou, Magdalini; Ditsworth, Dara; Kordasiewicz, Holly B; McAlonis-Downes, Melissa; Platoshyn, Oleksandr; Parone, Philippe A; Da Cruz, Sandrine; Clutario, Kevin M; Swing, Debbie; Tessarollo, Lino; Marsala, Martin; Shaw, Christopher E; Yeo, Gene W; Cleveland, Don W

    2013-02-19

    Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon degeneration and motor neuron death when expressed in mice at levels and in a cell type-selective pattern similar to endogenous TDP-43. Mutant TDP-43-dependent degeneration of lower motor neurons occurs without: (i) loss of TDP-43 from the corresponding nuclei, (ii) accumulation of TDP-43 aggregates, and (iii) accumulation of insoluble TDP-43. Computational analysis using splicing-sensitive microarrays demonstrates alterations of endogenous TDP-43-dependent alternative splicing events conferred by both human wild-type and mutant TDP-43(Q331K), but with high levels of mutant TDP-43 preferentially enhancing exon exclusion of some target pre-mRNAs affecting genes involved in neurological transmission and function. Comparison with splicing alterations following TDP-43 depletion demonstrates that TDP-43(Q331K) enhances normal TDP-43 splicing function for some RNA targets but loss-of-function for others. Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage. PMID:23382207

  17. Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice.

    PubMed

    Shkedi-Rafid, Shiri; Fenwick, Angela; Dheensa, Sandi; Lucassen, Anneke M

    2015-10-01

    This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic 'carrier' status to assess future reproductive risks. The study also examined participants' level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child's future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing. PMID:25370041

  18. Reactive macrophage activation syndrome possibly triggered by canakinumab in a patient with adult-onset Still's disease.

    PubMed

    Banse, Christopher; Vittecoq, Olivier; Benhamou, Ygal; Gauthier-Prieur, Maud; Lequerré, Thierry; Lévesque, Hervé

    2013-12-01

    Macrophage activation syndrome (MAS) is a rare and serious complication of adult-onset Still's disease. We describe a case in a 49-year-old woman with Still's disease refractory to glucocorticoids, methotrexate, and infliximab. Anakinra provided satisfactory disease control for 1 year, after which escape phenomenon occurred. After four tocilizumab injections, cutaneous melanoma developed. The persistent systemic manifestations prompted treatment with two canakinumab injections. Ten days later, she had a spiking fever, dyspnea, low back pain, abdominal pain, odynophagia, and hepatomegaly. Laboratory tests showed liver cytolysis (180 IU/L; N: 10-35), acute renal failure (creatinine, 407 μmol/L; N:50-100), thrombocytopenia (60 G/L; N: 150-400), leukocytosis (12,200/mm(3); N: 4000-10,000), hypertriglyceridemia (5070 mmol/L; N: 0.4-1.6), lactate dehydrogenase elevation (4824 IU/L; N: 135-250), and hyperferritinemia (97 761 μg/L; N:15-150). Examination of a bone marrow biopsy showed phagocytosis. Tests were negative for viruses and other infectious agents. Glucocorticoid therapy (1.5 mg/Kg/d) and intravenous polyvalent immunoglobulins (0.5 g/Kg/d) were given. Her condition improved despite the many factors of adverse prognostic significance (thrombocytopenia, absence of lymphadenopathy, and glucocorticoid therapy at diagnosis). This is the first reported case of MAS after canakinumab therapy in a patient with adult-onset Still's disease. PMID:23751410

  19. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension.

    PubMed

    Baserga, Mariana; Hale, Merica A; Wang, Zheng Ming; Yu, Xing; Callaway, Christopher W; McKnight, Robert A; Lane, Robert H

    2007-05-01

    Clinical and animal studies indicate that intrauterine growth restriction (IUGR) following uteroplacental insufficiency (UPI) reduces nephron number and predisposes toward renal insufficiency early in life and increased risk of adult-onset hypertension. In this study, we hypothesized that the inducible enzyme cyclooxygenase-2 (COX-2), a pivotal protein in nephrogenesis, constitutes a mechanism through which UPI and subsequent glucocorticoid overexposure can decrease nephron number. We further hypothesized that UPI downregulates the key enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which converts corticosterone to inert 11-dehydrocorticosterone, thereby protecting both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) from the actions of corticosterone. Following bilateral uterine ligation on the pregnant rat, UPI significantly decreased renal COX-2, 11beta-HSD2, and GR mRNA and protein levels, but upregulated expression of MR at birth. At day 21 of life, 11beta-HSD2, GR, and also MR mRNA and protein levels were downregulated. UPI did not affect blood pressures (BP) at day 21 of life but significantly increased systolic BP in both genders at day 140. We conclude that in our animal model, UPI decreases fetal COX-2 expression during a period of active nephrogenesis in the IUGR rat, which is also characterized by decreased nephron number and adult-onset hypertension. PMID:17272666

  20. Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice.

    PubMed

    Vasilopoulou, Catherine G; Constantinou, Caterina; Giannakopoulou, Dimitra; Giompres, Panagiotis; Margarity, Marigoula

    2016-10-01

    Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner. PMID:27317840

  1. Possible macrophage activation syndrome following initiation of adalimumab in a patient with adult-onset Still's disease.

    PubMed

    Souabni, Leila; Dridi, Leila; Ben Abdelghani, Kawther; Kassab, Selma; Chekili, Selma; Laater, Ahmed; Zakraoui, Leith

    2014-01-01

    Macrophage activation syndrome (MAS) has been rarely reported in the course of adult-onset Still's disease (AOSD) and in the majority of cases, it was triggered by an infection. Here, we report, to our knowledge, the first case of MAS occurring after adalimumab treatment initiation and not triggered by an infection. A 26-yearold woman with classical features of AOSD developed persistent fever, severe bicytopenia associated with extreme hyperferritinemia, hyponatremia and abnormal liver function tow months after the initiation of adalimumab treatment. The diagnosis of MAS was made without histological proof. The patient was treated with methylprednisolone pulse therapy and her condition improved. During the disease course, extensive studies could not identify any viral infection or other known underlying etiology for the reactive MAS. The adalimumab was incriminated in this complication. Currently, the patient is in remission on tocilizumab and low-dose prednisolone. PMID:25018831

  2. Wiki-Based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma: A New Paradigm in Sarcoma Evidence

    PubMed Central

    Neuhaus, S. J.; Thomas, D.; Desai, J.; Vuletich, C.; von Dincklage, J.; Olver, I.

    2015-01-01

    In 2013 Australia introduced Wiki-based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma. These guidelines utilized a customized MediaWiki software application for guideline development and are the first evidence-based guidelines for clinical management of sarcoma. This paper presents our experience with developing and implementing web-based interactive guidelines and reviews some of the challenges and lessons from adopting an evidence-based (rather than consensus-based) approach to clinical sarcoma guidelines. Digital guidelines can be easily updated with new evidence, continuously reviewed and widely disseminated. They provide an accessible method of enabling clinicians and consumers to access evidence-based clinical practice recommendations and, as evidenced by over 2000 views in the first four months after release, with 49% of those visits being from countries outside of Australia. The lessons learned have relevance to other rare cancers in addition to the international sarcoma community. PMID:25784832

  3. HPV Type 6 and 18 Coinfection in a Case of Adult-Onset Laryngeal Papillomatosis: Immunization with Gardasil.

    PubMed

    Fancello, Virginia; Melis, Andrea; Piana, Andrea Fausto; Castiglia, Paolo; Cossu, Andrea; Sotgiu, Giovanni; Bozzo, Corrado; King, Emma Victoria; Meloni, Francesco

    2015-01-01

    Laryngeal papillomatosis (LP) is a rare human papillomavirus (HPV) related disease that often requires multiple surgical interventions and residual impairment of voice is almost inevitable. We report the case of a patient with adult onset recurrent LP, showing moderate dysplasia and coinfection with HPV types 6 and 18. The tetravalent HPV vaccine Gardasil was prescribed off label, with the aim of triggering an immunogenic response and consequently reducing the probability of further recurrences. The patient was followed for 9 months with no sign of relapse of his LP. The postexposure use of the anti-HPV vaccine could represent a promising therapeutic agent in established LP. Unfortunately, the potential efficacy of this new therapeutic option in this situation has been suggested only by isolated case reports. Further controlled studies, with a longer follow-up and a larger sample size, are needed to assess efficacy of Gardasil in LP. PMID:26783482

  4. HPV Type 6 and 18 Coinfection in a Case of Adult-Onset Laryngeal Papillomatosis: Immunization with Gardasil

    PubMed Central

    Fancello, Virginia; Melis, Andrea; Piana, Andrea Fausto; Castiglia, Paolo; Cossu, Andrea; Sotgiu, Giovanni; Bozzo, Corrado; King, Emma Victoria; Meloni, Francesco

    2015-01-01

    Laryngeal papillomatosis (LP) is a rare human papillomavirus (HPV) related disease that often requires multiple surgical interventions and residual impairment of voice is almost inevitable. We report the case of a patient with adult onset recurrent LP, showing moderate dysplasia and coinfection with HPV types 6 and 18. The tetravalent HPV vaccine Gardasil was prescribed off label, with the aim of triggering an immunogenic response and consequently reducing the probability of further recurrences. The patient was followed for 9 months with no sign of relapse of his LP. The postexposure use of the anti-HPV vaccine could represent a promising therapeutic agent in established LP. Unfortunately, the potential efficacy of this new therapeutic option in this situation has been suggested only by isolated case reports. Further controlled studies, with a longer follow-up and a larger sample size, are needed to assess efficacy of Gardasil in LP. PMID:26783482

  5. Adult Onset of BRAFV600E-Mutated Langerhans Cell Histiocytosis with Cutaneous Involvement Successfully Diagnosed by Immunohistochemical Staining

    PubMed Central

    Tono, Hisayuki; Fujimura, Taku; Kakizaki, Aya; Furudate, Sadanori; Ishibashi, Masaya; Aiba, Setsuya

    2015-01-01

    Langerhans cell histiocytosis (LCH) is characterized by the clonal proliferation of Langerhans cells; it is categorized as a single-system disease with single or multifocal lesions, and as a multi-system disease with or without the risk of organ involvement. Although the skin is not categorized as a risk organ, the precise diagnosis of skin lesions is necessary to determine the protocol for the treatment of LCH. In this report, we describe a 28-year-old Japanese man with adult onset of BRAFV600E-mutated LCH with cutaneous involvement successfully diagnosed by immunohistochemical staining. Our report suggests that immunohistochemical staining for the BRAFV600E gene could be a diagnostic tool to determine the clinical type of LCH. PMID:26500535

  6. An autopsied case of sporadic adult-onset amyotrophic lateral sclerosis with FUS-positive basophilic inclusions.

    PubMed

    Matsuoka, Takeshi; Fujii, Naoki; Kondo, Akira; Iwaki, Akiko; Hokonohara, Toshihiro; Honda, Hiroyuki; Sasaki, Kensuke; Suzuki, Satoshi O; Iwaki, Toru

    2011-02-01

    Basophilic inclusions (BIs), which are characterized by their staining properties of being weakly argyrophilic, reactive with Nissl staining, and immunohistochemically negative for tau and transactive response (TAR) DNA-binding protein 43 (TDP-43), have been identified in patients with juvenile-onset amyotrophic lateral sclerosis (ALS) and adult-onset atypical ALS with ophthalmoplegia, autonomic dysfunction, cerebellar ataxia, or a frontal lobe syndrome. Mutations in the fused in sarcoma gene (FUS) have been reported in cases of familial and sporadic ALS, and FUS immunoreactivity has been demonstrated in basophilic inclusion body disease (BIBD), neuronal intermediate filament inclusion disease (NIFID), and atypical frontotemporal lobar degeneration with ubiquitin-positive and tau-negative inclusions (aFTLD-U). In the present study, we immunohistochemically and ultrastructurally studied an autopsy case of sporadic adult-onset ALS with numerous BIs. The patient presented with the classical clinical course of ALS since 75 years of age and died at age 79. Postmortem examination revealed that both Betz cells in the motor cortex and motor neurons in the spinal cord were affected. The substantia nigra was spared. Notably, BIs were frequently observed in the motor neurons of the anterior horns, the inferior olivary nuclei, and the basal nuclei of Meynert. BIs were immunopositive for p62, LC3, and FUS, but immunonegative for tau, TDP-43, and neurofilament. Ultrastructurally, BIs consisted of filamentous or granular structures associated with degenerated organelles with no limiting membrane. There were no Bunina bodies, skein-like inclusions, or Lewy-like inclusions. All exons and exon/intron boundaries of the FUS gene were sequenced but no mutations were identified. PMID:20573033

  7. Adult-Onset Fatal Neurohepatopathy in a Woman Caused by MPV17 Mutation.

    PubMed

    Mendelsohn, Bryce A; Mehta, Neil; Hameed, Bilal; Pekmezci, Melike; Packman, Seymour; Ralph, Jeffrey

    2014-01-01

    Hepatocerebral mitochondrial DNA depletion syndromes are classically considered diseases of early childhood, typically affecting the liver, peripheral, and central nervous systems with a rapidly progressive course. Evidence is emerging that initial symptom onset can extend into adulthood, though few such cases have been reported. We describe a 25-year-old woman who presented initially with secondary amenorrhea, followed by a megaloblastic anemia, lactic acidosis, leukoencephalopathy, progressive peripheral neuropathy, and liver cirrhosis. An apparently homozygous P98L mutation was identified in MPV17, a gene associated with a lethal infantile neurohepatopathy. Homozygosity for the same allele was recently reported in a man with a similar hepatic and neurologic phenotype. This is the first clinical report of an adult female with this disorder, and the first to describe amenorrhea and megaloblastic anemia as likely associated symptoms. PMID:24190800

  8. Two Siblings with Adolescent/Adult Onset Niemann-Pick Disease Type C in Korea.

    PubMed

    Lee, Su-Yun; Lee, Hyung Jin; Kim, Seong Hwan; Jeong, Young Jin; Jin, Hee Kyung; Bae, Jae-Sung; Cheon, Sang-Myung; Kim, Jae Woo

    2016-07-01

    Niemann-Pick disease, type C (NP-C), is caused by NPC1 or NPC2 gene mutations. Progressive neurological, psychiatric, and visceral symptoms are characteristic. Here, we present cases of a brother (Case 1) and sister (Case 2) in their mid-20s with gait disturbance and psychosis. For the Case 1, neurological examination revealed dystonia, ataxia, vertical supranuclear-gaze palsy (VSGP), and global cognitive impairment. Case 2 showed milder, but similar symptoms, with cortical atrophy. Abdominal computed tomography showed hepatosplenomegaly in both cases. NPC1 gene sequencing revealed compound heterozygote for exon 9 (c.1552C>T [R518W]) and exon 18 (c.2780C>T [A927V]). Filipin-staining tests were also positive. When a young patient with ataxia or dystonia shows VSGP, NP-C should be considered. PMID:27366019

  9. Noncirrhotic Extrahepatic Portosystemic Shunt Causing Adult-Onset Encephalopathy Treated with Endovascular Closure

    PubMed Central

    Elnekave, Eldad; Belenky, Eugenia; Van der Veer, Lindsley

    2015-01-01

    A 54-year-old woman presented with a six-month history of episodic confusion and progressive ataxia. A comprehensive metabolic panel was notable for elevated values of alkaline phosphatase (161 U/L), total bilirubin (1.5 mg/dL), and serum ammonia of 300 umol/L (normal range 9–47). Hepatitis panel, relevant serological tests, tumor markers (CA-19-9, CEA), and urea cycle enzyme studies were unrevealing. Lactulose and rifaximin therapy failed to normalize serum ammonia levels. Imaging revealed a structural vascular abnormality communicating between an enlarged inferior mesenteric vein and the left renal vein, measuring 16 mm in greatest diameter. The diagnosis of congenital extrahepatic portosystemic shunt was made and endovascular shunt closure was performed using a 22 mm Amplatzer II vascular plug. Within a day, serum ammonia levels normalized. Lactulose and rifaximin were discontinued, and confusion and ataxia resolved. PMID:26199783

  10. Two Siblings with Adolescent/Adult Onset Niemann-Pick Disease Type C in Korea

    PubMed Central

    2016-01-01

    Niemann–Pick disease, type C (NP-C), is caused by NPC1 or NPC2 gene mutations. Progressive neurological, psychiatric, and visceral symptoms are characteristic. Here, we present cases of a brother (Case 1) and sister (Case 2) in their mid-20s with gait disturbance and psychosis. For the Case 1, neurological examination revealed dystonia, ataxia, vertical supranuclear-gaze palsy (VSGP), and global cognitive impairment. Case 2 showed milder, but similar symptoms, with cortical atrophy. Abdominal computed tomography showed hepatosplenomegaly in both cases. NPC1 gene sequencing revealed compound heterozygote for exon 9 (c.1552C>T [R518W]) and exon 18 (c.2780C>T [A927V]). Filipin-staining tests were also positive. When a young patient with ataxia or dystonia shows VSGP, NP-C should be considered. PMID:27366019

  11. Adult-onset painful axonal polyneuropathy caused by a dominant NAGLU mutation

    PubMed Central

    Tétreault, Martine; Gonzalez, Michael; Dicaire, Marie-Josée; Allard, Pierre; Gehring, Kalle; Leblanc, Diane; Leclerc, Nadine; Schondorf, Ronald; Mathieu, Jean; Zuchner, Stephan

    2015-01-01

    Late-onset painful sensory neuropathies are usually acquired conditions associated with common diseases. Adult presentations of known hereditary forms are often accompanied by other organ involvement. We recruited a large French-Canadian family with a dominantly inherited late-onset painful sensory neuropathy. The main clinical feature is recurrent leg pain that progresses to constant painful paraesthesias in the feet and later the hands. As it evolves, some patients develop a mild sensory ataxia. We selected four affected individuals for whole exome sequencing. Analysis of rare variants shared by all cases led to a list of four candidate variants. Segregation analysis in all 45 recruited individuals has shown that only the p.Ile403Thr variant in the α-N-acetyl-glucosaminidase (NAGLU) gene segregates with the disease. Recessive NAGLU mutations cause the severe childhood lysosomal disease mucopolysacharidosis IIIB. Family members carrying the mutation showed a significant decrease of the enzymatic function (average 45%). The late-onset and variable severity of the symptoms may have precluded the description of such symptoms in parents of mucopolysaccharidosis IIIB cases. The identification of a dominant phenotype associated with a NAGLU mutation supports that some carriers of lysosomal enzyme mutations may develop later in life much milder phenotypes. PMID:25818867

  12. Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells

    PubMed Central

    Lopes, Carla; Aubert, Sophie; Bourgois-Rocha, Fany; Barnat, Monia; Rego, Ana Cristina; Déglon, Nicole

    2016-01-01

    Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington’s disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions. PMID:26863614

  13. Relationship between neuropsychological impairment and grey and white matter changes in adult-onset myotonic dystrophy type 1.

    PubMed

    Baldanzi, Sigrid; Cecchi, Paolo; Fabbri, Serena; Pesaresi, Ilaria; Simoncini, Costanza; Angelini, Corrado; Bonuccelli, Ubaldo; Cosottini, Mirco; Siciliano, Gabriele

    2016-01-01

    Myotonic dystrophy type 1 (DM1) has a wide phenotypic spectrum and potentially may affect central nervous system with mild to severe involvement. Our aim was to investigate grey matter (GM) and white matter (WM) structural alterations in a sample of adult-onset DM1 patients and to evaluate relationship with clinical and cognitive variables. Thirty DM1 patients underwent neuropsychological investigation and 3T-MRI protocol. GM and WM changes were evaluated calculating brain parenchymal fraction (BPF), voxel-based morphometry (VBM), white matter lesion load (LL% and Fazekas scale) and tract based spatial statistical (TBSS). Patients showed main impairment in tests exploring executive and mnesic domains with visuo-spatial involvement, significantly related to BPF. VBM revealed clusters of widespread GM reduction and TBSS revealed areas of decreased fractional anisotropy (FA) and increased radial diffusivity (RD), mean diffusivity (MD) and axial diffusivity (AD) in patients compared to a group of matched healthy controls. Multiple regression analyses showed areas of significant negative relationship between left temporal atrophy and verbal memory, between RD and mnesic and visuo-spatial cognitive domains, and between AD and verbal memory. TBSS results indicate that the involvement of normal appearance WM, beyond the signal changes detected with conventional MR imaging (Fazekas scale and LL%), was associated with neuropsychological deficit. These data suggest that disrupted complex neuronal networks can underlie cognitive-behavioural dysfunctions in DM1. PMID:27437180

  14. Adult-onset Kawasaki disease (mucocutaneous lymph node syndrome) and concurrent Coxsackievirus A4 infection: a case report

    PubMed Central

    Ueda, Yuki; Kenzaka, Tsuneaki; Noda, Ayako; Yamamoto, Yu; Matsumura, Masami

    2015-01-01

    Introduction Kawasaki disease (KD) most commonly develops in infants, although its specific cause is still unclear. We report here a rare case of adult-onset KD which revealed to be concurrently infected by Coxsackievirus A4. Case presentation The patient was a 37-year-old Japanese man who presented with fever, exanthema, changes in the peripheral extremities, bilateral non-exudative conjunctival injection, and changes in the oropharynx, signs that meet the diagnostic criteria for KD defined by the Centers for Disease Control and Prevention. In this case, the patient had a significantly high antibody titer for Coxsackievirus A4, which led us to presume that the occurrence of KD was concurrent Coxsackievirus A4 infection. Conclusion We reported a very rare case of KD which suggests that the disease can be concurrent Coxsackievirus A4 infection. Although KD is an acute childhood disease, with fever as one of the principal features, KD should also be considered in the differential diagnosis when adult patients present with a fever of unknown cause associated with a rash. PMID:26491373

  15. Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction.

    PubMed

    Amenta, F; Tayebati, S K

    2008-01-01

    Acetylcholine (ACh) is a neurotransmitter widely diffused in central, peripheral, autonomic and enteric nervous system. This paper has reviewed the main mechanisms of ACh synthesis, storage, and release. Presynaptic choline transport supports ACh production and release, and cholinergic terminals express a unique transporter critical for neurotransmitter release. Neurons cannot synthesize choline, which is ultimately derived from the diet and is delivered through the blood stream. ACh released from cholinergic synapses is hydrolyzed by acetylcholinesterase into choline and acetyl coenzyme A and almost 50% of choline derived from ACh hydrolysis is recovered by a high-affinity choline transporter. Parallel with the development of cholinergic hypothesis of geriatric memory dysfunction, cholinergic precursor loading strategy was tried for treating cognitive impairment occurring in Alzheimer's disease. Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine), whereas for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) or alpha-glyceryl-phosphorylcholine (choline alphoscerate) a modest improvement of cognitive dysfunction in adult-onset dementia disorders is documented. These inconsistencies have probably a metabolic explanation. Free choline administration increases brain choline availability but it does not increase ACh synthesis/or release. Cholinergic precursors to serve for ACh biosynthesis should be incorporate and stored into phospholipids in brain. It is probable that appropriate ACh precursors and other correlated molecules (natural or synthesized) could represent a tool for developing therapeutic strategies by revisiting and updating treatments/supplementations coming out from this therapeutic stalemate. PMID:18289004

  16. Adult-onset multiple acyl CoA dehydrogenation deficiency associated with an abnormal isoenzyme pattern of serum lactate dehydrogenase.

    PubMed

    Sugai, Fuminobu; Baba, Kousuke; Toyooka, Keiko; Liang, Wen-Chen; Nishino, Ichizo; Yamadera, Misaki; Sumi, Hisae; Fujimura, Harutoshi; Nishikawa, Yoshiro

    2012-02-01

    We report a case of a 37 year-old male with multiple acyl-CoA dehydrogenation deficiency (MADD). The patient had suffered from exercise intolerance in his hip and thigh muscles for one year. Then, restriction of carbohydrates for a diet made his symptoms rapidly deteriorate. Blood test revealed compound heterozygosity for two novel missense mutations in the electron transfer flavoprotein dehydrogenase gene (ETFDH), and an abnormal LDH isoenzyme pattern: LDH-1 (60.0%) and LDH-2 (26.0%) predominated with abnormally elevated LDH-1/LDH-2 ratio (2.3), compared with muscle-derived LDH-5 (4.0%). Oral riboflavin treatment significantly improved his exercise intolerance and the LDH profile: LDH-1 (34.4%), LDH-2 (34.9%), LDH-5 (6.9%) and LDH-1/LDH-2 ratio (1.0). The abnormal LDH isoenzyme pattern may be one feature of adult-onset MADD selectively affecting type I muscle fibers with relatively high LDH-1 content. PMID:21907580

  17. Adult-onset Still's disease: an Italian multicentre retrospective observational study of manifestations and treatments in 245 patients.

    PubMed

    Sfriso, Paolo; Priori, Roberta; Valesini, Guido; Rossi, Silvia; Montecucco, Carlo Maurizio; D'Ascanio, Anna; Carli, Linda; Bombardieri, Stefano; LaSelva, Gaetana; Iannone, Florenzo; Lapadula, Giovanni; Alivernini, Stefano; Ferraccioli, Gianfranco; Colaci, Michele; Ferri, Clodoveo; Iacono, Daniela; Valentini, Gabriele; Costa, Luisa; Scarpa, Raffaele; LoMonaco, Andrea; Bagnari, Valentina; Govoni, Marcello; Piazza, Ilaria; Adami, Silvano; Ciccia, Francesco; Triolo, Giovanni; Alessandri, Elisa; Cutolo, Maurizio; Cantarini, Luca; Galeazzi, Mauro; Ruscitti, Piero; Giacomelli, Roberto; Caso, Francesco; Galozzi, Paola; Punzi, Leonardo

    2016-07-01

    Adult-onset Still's disease (AOSD) is a systemic inflammatory condition of unknown aetiology characterized by typical episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. Given the lack of data in Italian series, we promote a multicentric data collection to characterize the clinical phenotype of Italian patients with AOSD. Data from 245 subjects diagnosed with AOSD were collected by 15 centres between March and May 2013. The diagnosis was made following Yamaguchi's criteria. Data regarding clinical manifestations, laboratory features, disease course and treatments were reported and compared with those presented in other published series of different ethnicity. The most frequent features were the following: arthritis (93 %), pyrexia (92.6 %), leukocytosis (89 %), negative ANA (90.4 %) and neutrophilia (82 %). As compared to other North American, North European, Middle Eastern and Far Eastern cohorts, Italian data show differences in clinical and laboratory findings. Regarding the treatments, in 21.9 % of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biologics have been shown to be effective in 48 to 58 patients. This retrospective work summarizes the largest Italian multicentre series of AOSD patients and presents clinical and laboratory features that appear to be influenced by the ethnicity of the affected subjects. PMID:27207567

  18. Adult-onset type 1 diabetes patients display decreased IGRP-specific Tr1 cells in blood.

    PubMed

    Chujo, Daisuke; Nguyen, Thien-Son; Foucat, Emile; Blankenship, Derek; Banchereau, Jacques; Nepom, Gerald T; Chaussabel, Damien; Ueno, Hideki

    2015-12-01

    The breakdown of immune tolerance against islet antigens causes type 1 diabetes (T1D). The antigens associated with adult-onset T1D (AT1D) remain largely undefined. It is possible that AT1D patients display a unique type of CD4(+) T cells specific for a certain islet antigen. Here we analyzed the cytokine production profiles of CD4(+) helper T (Th) cells that are specific for three islet antigens; GAD65, preproinsulin, and IGRP in patients with AT1D, juvenile-onset T1D (JT1D), and age-, gender- and human leukocyte antigen (HLA)-matched control adults. While IGRP-specific Th cells in AT1D patients were dominantly Th1 cells, IGRP-specific Th cells in control adults and JT1D patients were dominantly Th2 and T regulatory type 1 (Tr1) cells. Notably, the frequency of IGRP-specific Tr1 cells was significantly lower in AT1D patients than in control adults and JT1D patients. In conclusion, our study suggests that IGRP-specific Th cells play a unique pathogenic role in AT1D. PMID:26341315

  19. Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review.

    PubMed

    Ogaki, Kotaro; Koga, Shunsuke; Aoki, Naoya; Lin, Wenlang; Suzuki, Kinuko; Ross, Owen A; Dickson, Dennis W

    2016-02-01

    X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy-confirmed cases exceedingly rare. We report a 69-year-old White man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison's disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of MSA. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting the optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be considered in the

  20. Experiences of Racism and the Incidence of Adult-Onset Asthma in the Black Women’s Health Study

    PubMed Central

    Yu, Jeffrey; O’Connor, George T.; Brown, Timothy A.; Cozier, Yvette C.; Palmer, Julie R.; Rosenberg, Lynn

    2014-01-01

    Background: Chronic stress resulting from experiences of racism may increase the incidence of adult-onset asthma through effects on the immune system and the airways. We conducted prospective analyses of the relation of experiences of racism with asthma incidence in the Black Women’s Health Study, a prospective cohort of black women in the United States followed since 1995 with mailed biennial questionnaires. Methods: Among 38,142 participants followed from 1997 to 2011, 1,068 reported incident asthma. An everyday racism score was created based on five questions asked in 1997 and 2009 about the frequency in daily life of experiences of racism (eg, poor service in stores), and a lifetime racism score was based on questions about racism on the job, in housing, and by police. We used Cox regression models to derive multivariable incidence rate ratios (IRRs) and 95% CIs for categories of each racism score in relation to incident asthma. Results: The IRRs were 1.45 (95% CI, 1.19-1.78) for the highest compared with the lowest quartile of the 1997 everyday racism score (P for trend <.0001) and 1.44 (95% CI, 1.18-1.75) for the highest compared with the lowest category of 1997 lifetime racism. Among women who reported the same levels of racism in 1997 and 2009, the IRRs for the highest categories of everyday and lifetime racism were 2.12 (95% CI, 1.55-2.91) and 1.66 (95% CI, 1.20-2.30), respectively. Conclusions: Given the high prevalence of experiences of racism and asthma in black women in the United States, a positive association between racism and asthma is of public health importance. PMID:23887828

  1. Adult onset Still's disease (AOSD) in the era of biologic therapies: dichotomous view for cytokine and clinical expressions.

    PubMed

    Maria, Alexandre Thibault Jacques; Le Quellec, Alain; Jorgensen, Christian; Touitou, Isabelle; Rivière, Sophie; Guilpain, Philippe

    2014-11-01

    Adult onset Still's disease (AOSD) is a rare inflammatory disorder characterized by hectic spiking fever, evanescent rash and joint involvement. Prognosis is highly variable upon disease course and specific involvements, ranging from benign and limited outcome to chronic destructive polyarthritis and/or life-threatening events in case of visceral complications or reactive hemophagocytic lymphohistiocytosis (RHL). AOSD remains a debatable entity at the frontiers of autoimmune diseases and autoinflammatory disorders. The pivotal role of macrophage cell activation leading to a typical Th1 cytokine storm is now well established in AOSD, and confirmed by the benefits using treatments targeting TNF-α, IL-1β or IL-6 in refractory patients. However, it remains difficult to determine predictive factors of outcome and to draw guidelines for patient management. Herein, reviewing literature and relying on our experience in a series of 8 refractory AOSD patients, we question nosology and postulate that different cytokine patterns could underlie contrasting clinical expressions, as well as responses to targeted therapies. We therefore propose to dichotomize AOSD according to its clinical presentation. On the one hand, 'systemic AOSD' patients, exhibiting the highest inflammation process driven by excessive IL-18, IL-1β and IL-6 production, would be at risk of life-threatening complications (such as multivisceral involvements and RHL), and would preferentially respond to IL-1β and IL-6 antagonists. On the other hand, 'rheumatic AOSD' patients, exhibiting pre-eminence of joint involvement driven by IL-8 and IFN-γ production, would be at risk of articular destructions, and would preferentially respond to TNF-α blockers. PMID:25183244

  2. Parenchymal lung involvement in adult-onset Still disease: A STROBE-compliant case series and literature review.

    PubMed

    Gerfaud-Valentin, Mathieu; Cottin, Vincent; Jamilloux, Yvan; Hot, Arnaud; Gaillard-Coadon, Agathe; Durieu, Isabelle; Broussolle, Christiane; Iwaz, Jean; Sève, Pascal

    2016-07-01

    Parenchymal lung involvement (PLI) in adult-onset Still's disease (AOSD) has seldom, if ever, been studied. We examine here retrospective cohort AOSD cases and present a review of the literature (1971-2014) on AOSD-related PLI cases.Patients with PLI were identified in 57 AOSD cases. For inclusion, the patients had to fulfill Yamaguchi or Fautrel classification criteria, show respiratory symptoms, and have imaging evidence of pulmonary involvement, and data allowing exclusion of infectious, cardiogenic, toxic, or iatrogenic cause of PLI should be available. This AOSD + PLI group was compared with a control group (non-PLI-complicated AOSD cases from the same cohort).AOSD + PLI was found in 3 out of the 57 patients with AOSD (5.3%) and the literature mentioned 27 patients. Among these 30 AOSD + PLI cases, 12 presented an acute respiratory distress syndrome (ARDS) and the remaining 18 another PLI. In the latter, a nonspecific interstitial pneumonia computed tomography pattern prevailed in the lower lobes, pulmonary function tests showed a restrictive lung function, the alveolar differential cell count was neutrophilic in half of the cases, and the histological findings were consistent with bronchiolitis and nonspecific interstitial pneumonia. Corticosteroids were fully efficient in all but 3 patients. Ten out of 12 ARDS cases occurred during the first year of the disease course. All ARDS-complicated AOSD cases received corticosteroids with favorable outcomes in 10 (2 deceased). Most PLIs occurred during the systemic onset of AOSD.PLI may occur in 5% of AOSDs, of which ARDS is the most severe. Very often, corticosteroids are efficient in controlling this complication. PMID:27472698

  3. Comparison of Glomerular Transcriptome Profiles of Adult-Onset Steroid Sensitive Focal Segmental Glomerulosclerosis and Minimal Change Disease

    PubMed Central

    Ren, Hong; Liu, Jian; Zhang, Weijia; Wei, Chengguo; Xu, Jing; Zhang, Wen; Li, Xiao; Wang, Weiming; Lv, Danfeng; He, John Cijiang; Chen, Nan

    2015-01-01

    Objective To search for biomarkers to differentiate primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Methods We isolated glomeruli from kidney biopsies of 6 patients with adult-onset steroid sensitiveFSGS and 5 patients with MCD, and compared the profiles of glomerular transcriptomes between the two groups of patients using microarray analysis. Results Analysis of differential expressed genes (DEGs) revealed that up-regulated DEGs in FSGS patients compared with MCD patients were primarily involved in spermatogenesis, gamete generation, regulation of muscle contraction, response to unfolded protein, cell proliferation and skeletal system development. The down-regulated DEGs were primarily related to metabolic process, intracellular transport, oxidation/reduction andestablishment of intracellular localization. We validated the expression of the top 6 up-regulated and top 6 down-regulated DEGs using real-time PCR. Membrane metallo-endopeptidase (MME) is a down-regulated gene that was previously identified as a key gene for kidney development. Immunostaining confirmed that the protein expression of MME decreased significantly in FSGS kidneys compared with MCD kidneys. Conclusions This report was the first study to examine transcriptomes in Chinese patients with various glomerular diseases. Expressions of MME both in RNA and protein level decreased significantly in glomeruli of FSGS kidneys compared with MCD kidneys. Our data suggested that MME might play a role in the normal physiological function of podocytes and a decrease in MME expression might be related to podocyte injury. We also identified genes and pathways specific for FSGS versus MCD, and our data could help identify potential new biomarkers for the differential diagnosis between these two diseases. PMID:26536600

  4. Morphea in Adults and Children Cohort VI: A cross-sectional comparison of outcomes between adults with pediatric-onset and adult-onset morphea

    PubMed Central

    Condie, Daniel; Grabell, Daniel; Jacobe, Heidi

    2014-01-01

    Objective Few studies have looked at outcomes of adults with pediatric-onset morphea. The objective of the present study was to compare clinical outcomes and health-related quality of life in adults with pediatric-onset morphea to those of patients with adult-onset morphea. Methods Participants in the study were drawn from the Morphea in Adults and Children Cohort and included 68 adults with pediatric-onset morphea and 234 patients with adult-onset morphea. Outcome measures included the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), physical exam findings, and quality of life questionnaires. Results Adults with pediatric-onset morphea were younger, had longer disease duration, and were more likely to have the linear subtype of morphea. Patients with pediatric-onset disease were less likely to have active disease. Among patients with active disease, those with pediatric-onset morphea had less disease activity as measured by the LoSCAT. Patients with pediatric-onset disease had higher disease damage as measured by the Physician Global Assessment of Damage, but similar disease damage as measured by the Localized Scleroderma Skin Damage Index. Patients with pediatric-onset disease had more favorable quality of life scores for all measures that reached statistical significance. Conclusion Adults with pediatric-onset morphea differ from patients with adult-onset disease with respect to subtype, disease activity, disease damage, and health-related quality of life. PMID:25156342

  5. Interleukin 1 inhibition with anakinra in adult-onset Still disease: a meta-analysis of its efficacy and safety

    PubMed Central

    Hong, Dongsheng; Yang, Zhihai; Han, Shuyin; Liang, Xingguang; Ma, Kuifen; Zhang, Xingguo

    2014-01-01

    Background Anakinra is the first interleukin-1 inhibitor to be used in clinical practice, and recent evidence showed that interleukin-1 plays a pivotal role in the pathogenesis of adult-onset Still disease (AoSD). However, data concerning efficacy with anakinra use in different clinical trials has not been evaluated, and the overall remission of AoSD with anakinra treatment has not been well defined. Methods We conducted a search on Embase, PubMed, and the Cochrane Library for relevant trials. Statistical analyses were conducted to calculate the overall remission rates, odds ratios (OR), and 95% confidence intervals (CI), by using either random effects or fixed effect models according to the heterogeneity. Results Of the 273 articles that were identified, 265 were excluded. Eight studies were eligible for inclusion. The overall remission rate and complete remission rate of anakinra in AoSD patients were 81.66% (95% CI: 69.51%–89.69%) and 66.75% (95% CI: 59.94%–75.3%), respectively. Compared with the controls, the use of anakinra was associated with a significant remission in AoSD, with an OR of 0.16 (95% CI: 0.06–0.44, P=0.0005). There were also significant reductions of the dosage of corticosteroid (mean difference =21.19) (95% CI: 13.2–29.18, P<0.0001) from anakinra onset to the latest follow up time. Clinical and laboratory parameters were all improved, and anakinra was well tolerated in patients with AoSD. No evidence of publication bias was observed. Conclusion Our study has shown that anakinra is effective in remitting the manifestations of AoSD, with reduction of the dose of corticosteroid in patients with AoSD. Further, anakinra therapy was not associated with increased risk of adverse events, and it was well tolerated in patients with AoSD. Further research is still recommended to investigate these findings. PMID:25473268

  6. Annual Research Review: Current limitations and future directions in MRI studies of child- and adult-onset developmental psychopathologies

    PubMed Central

    Horga, Guillermo; Kaur, Tejal; Peterson, Bradley S.

    2014-01-01

    The widespread use of magnetic resonance imaging (MRI) in the study of child- and adult-onset developmental psychopathologies has generated many investigations that have measured brain structure and function in vivo throughout development, often generating great excitement over our ability to visualize the living, developing brain using the attractive, even seductive images that these studies produce. Often lost in this excitement is the recognition that brain imaging generally, and MRI in particular, is simply a technology, one that does not fundamentally differ from any other technology, be it a blood test, a genotyping assay, a biochemical assay, or behavioral test. No technology alone can generate valid scientific findings. Rather, it is only technology coupled with a strong experimental design that can generate valid and reproducible findings that lead to new insights into the mechanisms of disease and therapeutic response. In this review we discuss selected studies to illustrate the most common and important limitations of MRI study designs as most commonly implemented thus far, as well as the misunderstanding that the interpretations of findings from those studies can create for our theories of developmental psychopathologies. Those limitations are in large part responsible thus far for the generally poor reproducibility of findings across studies, poor generalizability to the larger population, failure to identify developmental trajectories, inability to distinguish causes from effects of illness, and poor ability to infer causal mechanisms in most MRI studies of developmental psychopathologies. For each of these limitations in study design and the difficulties they entail for the interpretation of findings, we discuss various approaches that numerous laboratories are now taking to address those difficulties, which have in common the yoking of brain imaging technologies to studies with inherently stronger designs that permit more valid and more powerful

  7. Rearranged Anaplastic Lymphoma Kinase (ALK) Gene in Adult-Onset Papillary Thyroid Cancer Amongst Atomic Bomb Survivors

    PubMed Central

    Mukai, Mayumi; Takahashi, Keiko; Hayashi, Yuzo; Nakachi, Kei; Kusunoki, Yoichiro

    2012-01-01

    rearrangements, being observed in 6 of 10 PTC cases with ALK rearrangements versus 2 of 15 cases with no ALK rearrangements. The six radiation-exposed cases of PTC harboring both ALK rearrangements and solid/trabecular-like architecture were associated with higher radiation doses and younger ages at the time of the A-bombing and at diagnosis compared to the other 19 PTC with no detectable gene alterations. Conclusion Our findings suggest that ALK rearrangements are involved in the development of radiation-induced adult-onset PTC. PMID:23050789

  8. Caenorhabditis elegans dnj-14, the orthologue of the DNAJC5 gene mutated in adult onset neuronal ceroid lipofuscinosis, provides a new platform for neuroprotective drug screening and identifies a SIR-2.1-independent action of resveratrol.

    PubMed

    Kashyap, Sudhanva S; Johnson, James R; McCue, Hannah V; Chen, Xi; Edmonds, Matthew J; Ayala, Mimieveshiofuo; Graham, Margaret E; Jenn, Robert C; Barclay, Jeff W; Burgoyne, Robert D; Morgan, Alan

    2014-11-15

    Adult onset neuronal lipofuscinosis (ANCL) is a human neurodegenerative disorder characterized by progressive neuronal dysfunction and premature death. Recently, the mutations that cause ANCL were mapped to the DNAJC5 gene, which encodes cysteine string protein alpha. We show here that mutating dnj-14, the Caenorhabditis elegans orthologue of DNAJC5, results in shortened lifespan and a small impairment of locomotion and neurotransmission. Mutant dnj-14 worms also exhibited age-dependent neurodegeneration of sensory neurons, which was preceded by severe progressive chemosensory defects. A focussed chemical screen revealed that resveratrol could ameliorate dnj-14 mutant phenotypes, an effect mimicked by the cAMP phosphodiesterase inhibitor, rolipram. In contrast to other worm neurodegeneration models, activation of the Sirtuin, SIR-2.1, was not required, as sir-2.1; dnj-14 double mutants showed full lifespan rescue by resveratrol. The Sirtuin-independent neuroprotective action of resveratrol revealed here suggests potential therapeutic applications for ANCL and possibly other human neurodegenerative diseases. PMID:24947438

  9. When uncommon and common coalesce: adult onset Still's disease associated with breast augmentation as part of autoimmune syndrome induced by adjuvants (ASIA).

    PubMed

    Dagan, A; Kogan, M; Shoenfeld, Y; Segal, G

    2016-06-01

    Adult onset Still's disease (AOSD) is an uncommon, multisystemic, auto-inflammatory disorder, while breast augmentation is a very common cosmetic procedure. We describe a case in which these two coalesce, AOSD, manifested with pleuritis and pericarditis, developed after breast mammoplasty. The pathogenetic, missing link, behind the development of AOSD following mammoplasty, is thought to be the autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). We reviewed other cases of AOSD associated with breast mammoplasty published to date and the literature regarding AOSD and ASIA syndrome. The review is followed by a short debate of whether silicone implants should be explanted in similar, future cases. PMID:25604318

  10. Adult-Onset Deficiency in Growth Hormone and Insulin-Like Growth Factor-I Alters Oligodendrocyte Turnover in the Corpus Callosum

    PubMed Central

    Hua, Kun; Forbes, M. Elizabeth; Lichtenwalner, Robin J.; Sonntag, William E.; Riddle, David R.

    2009-01-01

    Growth hormone (GH) and insulin-like growth factor-I (IGF-I) provide trophic support during development and also appear to influence cell structure, function and replacement in the adult brain. Recent studies demonstrated effects of the GH/IGF-I axis on adult neurogenesis, but it is unclear whether the GH/IGF-I axis influences glial turnover in the normal adult brain. In the current study we used a selective model of adult-onset GH and IGF-I deficiency to evaluate the role of GH and IGF-I in regulating glial proliferation and survival in the adult corpus callosum. GH/IGF-I-deficient dwarf rats of the Lewis strain were made GH/IGF-I replete via twice daily injections of GH starting at postnatal day 28 (P28), approximately the age at which GH pulse amplitude increases in developing rodents. GH/IGF-I deficiency was initiated in adulthood by removing animals from GH treatment. Quantitative analyses revealed that adult-onset GH/IGF-I deficiency decreased cell proliferation in the white matter and decreased the survival of newborn oligodendrocytes. These findings are consistent with the hypothesis that aging-related changes in the GH/IGF-I axis produce deficits in ongoing turnover of oligodendrocytes, which may contribute to aging-related cognitive changes and deficits in remyelination after injury. PMID:19115393

  11. Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation.

    PubMed Central

    Hanna, M G; Nelson, I; Sweeney, M G; Cooper, J M; Watkins, P J; Morgan-Hughes, J A; Harding, A E

    1995-01-01

    We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus. Images Figure 1 Figure 3 Figure 4 PMID:7726155

  12. Adult-onset hypothyroidism and the cerebral metabolism of (1,2-13C2) acetate as detected by 13C nuclear magnetic resonance.

    PubMed

    Chapa, F; Künnecke, B; Calvo, R; Escobar del Rey, F; Morreale de Escobar, G; Cerdán, S

    1995-01-01

    The effects of adult-onset hypothyroidism on the metabolic compartmentation of the cerebral tricarboxylic acid cycle and the gamma-aminobutyric acid (GABA) shunt have been investigated by 13C nuclear magnetic resonance spectroscopy. Rats thyroidectomized as adults and age-matched controls were infused in the right jugular vein with unlabeled or (1,2-13C2) acetate solutions for 60 min. At the end of the infusion, the brains were frozen in situ and perchloric acid extracts were prepared and analyzed by 13C nuclear magnetic resonance and reverse-phase HPLC. Thyroidectomized animals showed a decrease in the incorporation of 13C from (1,2-13C2) acetate in cerebral metabolites and an increase in the concentrations of unlabeled glutamate and GABA. Computer-assisted interpretation of the 13C multiplets observed for the carbons of glutamate, glutamine, and GABA indicated that adult-onset hypothyroidism produced 1) a decrease in the contribution of infused (1,2-13C2) acetate to the glial tricarboxylic acid cycle; 2) an increase in the contribution of unlabeled acetyl-CoA to the neuronal tricarboxylic acid cycle; and 3) impairments in the exchange of glutamate, glutamine, and GABA between the neuronal and glial compartments. Despite the fact that the adult brain has often been considered metabolically unresponsive to thyroid hormone status, present results show metabolic alterations in the neuronal and glial compartments that are reversible with substitution therapy. PMID:7828544

  13. Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann-Pick disease type C patients treated with miglustat.

    PubMed

    Bowman, Elizabeth A; Walterfang, Mark; Abel, Larry; Desmond, Patricia; Fahey, Michael; Velakoulis, Dennis

    2015-09-01

    Niemann-Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment available to date is miglustat, an iminosugar inhibiting the accumulation of lipid by-products in neurons. This study explored how changes in cerebellar grey and white matter volumes, and in subcortical volumes, related to patient treatment status and disability and ataxia ratings. Nine adult-onset NPC patients and 17 matched controls underwent T1-weighted MRI. One patient was not receiving miglustat, and pre-treatment data were available for a further patient. Semi-automated cerebellar and subcortical segmentation was undertaken, and the rates of change in putamen, hippocampal, thalamic and caudal volumes, and grey and white matter cerebellar volumes, were compared to rates of change in Iturriaga disability score, Brief Ataxia Rating Scale (BARS), and horizontal saccadic gain. Untreated NPC patients appeared to lose cerebellar grey and white matter, bilateral thalamic volume, and right caudate volume faster than treated patients. Cerebellar grey matter volume loss and volume loss in the left thalamus were significantly correlated with Iturriaga disability scale changes. Change in both cerebellar grey and white matter was correlated with decrease in horizontal saccadic gain, but not with change in BARS. This is the first study to examine longitudinal treatment effects of miglustat on cerebellar and subcortical volumes in patients with adult-onset NPC, and is evidence that miglustat may have a protective effect on cerebellar and subcortical structure and function. PMID:26092521

  14. Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: Different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation

    SciTech Connect

    Hanna, M.G.; Nelson, I.; Sweeney, M.G.; Cooper, J.M.; Watkins, P.J.; Morgan-Hughes, J.A.; Harding, A.E.

    1995-05-01

    We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus. 43 refs., 4 figs., 1 tab.

  15. Is Antimicrobial Resistance a Slowly Emerging Disaster?

    PubMed Central

    Viens, A. M.

    2015-01-01

    The problem of antimicrobial resistance is so dire that people are predicting that the era of antibiotics may be coming to an end, ushering in a ‘post-antibiotic’ era. A comprehensive policy response is therefore urgently needed. A part of this response will require framing the problem in such a way that adequately reflects its nature as well as encompassing an approach that has the best prospect of success. This paper considers framing the problem as a slowly emerging disaster, including its potential benefits and difficulties, from a conceptual and policy perspective. PMID:26566396

  16. Differences in B7 and CD28 family gene expression in the peripheral blood between newly diagnosed young-onset and adult-onset type 1 diabetes patients.

    PubMed

    Pruul, K; Kisand, K; Alnek, K; Metsküla, K; Reimand, K; Heilman, K; Peet, A; Varik, K; Peetsalu, M; Einberg, Ü; Tillmann, V; Uibo, R

    2015-09-01

    Type-1 diabetes (T1D) is a heterogeneous autoimmune disease, and there are pathogenetic differences between young- and adult-onset T1D patients. We hypothesized that the expressions of genes involved in costimulatory immune system pathways in peripheral blood are differently regulated in young- and adult-onset T1D. Study group I consisted of 80 children, adolescents, and young adults (age range 1.4-21.4 y; 31 controls and 49 T1D patients). Study group II consisted of 48 adults (age range 22.0-78.4 y; 30 controls and 18 T1D patients). The mRNA expression levels of CD86, CD28, CD25, CD226, CD40, BTLA, GITR, PDCD1, FoxP3, TGF-β, ICOS, sCTLA4, flCTLA4, and CD80 were measured in peripheral blood. Genetic polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4; rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were analyzed. In group I, there was significantly lower expression of CD226 in T1D patients than in the controls. In group II, there were significantly higher expression levels of CD86 and TGF-β in T1D patients than in the controls. In the T1D patients in group I, the upregulated CD80 expression correlated with the expression of both CTLA4 splice variants (sCTLA4 and flCTLA4). In contrast, in group II, upregulated CD86 correlated with TGF-β and CD25. In group I, the inhibitory CD80-CTLA4 pathway was activated, whereas, in group II, the activation CD86-CD28 pathway and TGF-β production were activated. These results emphasize the differences between young-onset and adult-onset T1D in the regulation of costimulatory pathways. These differences should be considered when developing novel treatments for T1D. PMID:25980680

  17. Slowly rotating pulsars and magnetic field decay

    NASA Astrophysics Data System (ADS)

    Han, J. L.

    1997-02-01

    Two dozen long period pulsars are separated from the swarm of ordinary pulsars by an obvious gap in the P versus Sd diagram (where Sd=log˙(P)+21.0), with a plausible upper boundary for ordinary pulsars. Possible pulsar evolutionary tracks are discussed to explain the diagram in terms of previously suggested scenarios of magnetic field decay. The (P-Sd) diagram is difficult to understand if there is no magnetic field decay during the active life of pulsars. However, if the magnetic fields of neutron stars decay exponentially, almost all slowly rotating pulsars must have been injected with a very long initial spin period of about 2 seconds, which seems impossible. Based on qualitative analyses, it is concluded that magnetic fields of neutron stars decay as a power-law, with a time scale related to the initial field strengths. The plausible boundary and the gap are suggested to naturally divide pulsars with distinct magnetic "genes", ie. pulsars which were born from strongly magnetized progenitors -- such as Bp stars, and pulsars born from normal massive stars. The possibility remains open that a fraction of slowly rotating pulsars were injected with long initial spin periods, while others would have a classical pulsar evolution history. It is suggested that PSR B1849+00 was born in the supernova remnant Kes-79 with an initial period of about 2 seconds.

  18. Incidence of Adult-onset Asthma After Hypothetical Interventions on Body Mass Index and Physical Activity: An Application of the Parametric G-Formula

    PubMed Central

    Garcia-Aymerich, Judith; Varraso, Raphaëlle; Danaei, Goodarz; Camargo,, Carlos A.; Hernán, Miguel A.

    2014-01-01

    High body mass index (BMI) (calculated as weight (kg)/height (m)2) is associated with increased asthma risk, but uncertainty persists about the role of physical activity. We estimated the independent and joint associations of hypothetical interventions on BMI and physical activity with the risk of adult-onset asthma in 76,470 asthma-free women from the Nurses’ Health Study who were followed between 1988 and 1998. Information about asthma, BMI, physical activity, and other factors was updated every 2 years. We used the parametric g-formula to estimate the 10-year asthma risk in the following 4 scenarios: no intervention, 5% BMI reduction in a 2-year period for those who were overweight or obese, at least 2.5 hours/week of moderate-to-vigorous physical activity, and both of the previous 2 interventions. At baseline, women had a mean age of 55 (standard deviation, 7) years and a mean BMI of 25.4 (standard deviation, 4.8). Median time spent in physical activity was 0.7 hours/week. During follow-up, 1,146 women developed asthma. The 10-year asthma risk under no intervention was 1.5%. Compared with no intervention, the population risk ratios were 0.96 (95% confidence interval (CI): 0.93, 0.99) under the BMI intervention, 0.96 (95% CI: 0.81, 1.10) under the physical activity intervention, and 0.92 (95% CI: 0.78, 1.06) under the joint intervention. Interventions on BMI and physical activity may have a modest impact on the risk of adult-onset asthma in this population of US women. PMID:24107616

  19. Trap models with slowly decorrelating observables

    NASA Astrophysics Data System (ADS)

    Sollich, Peter

    2006-03-01

    We study the correlation and response dynamics of trap models of glassy dynamics, considering observables that only partially decorrelate with every jump. This is inspired by recent work on a microscopic realization of such models, which found strikingly simple linear out-of-equilibrium fluctuation-dissipation relations in the limit of slow decorrelation. For the Barrat and Mézard model with its entropic barriers we obtain exact results at zero-temperature T for arbitrary decorrelation factor κ. These are then extended to nonzero T, where the qualitative scaling behaviour and all scaling exponents can still be found analytically. Unexpectedly, the choice of transition rates (Glauber versus Metropolis) affects not just prefactors but also some exponents. In the limit of slow decorrelation even complete scaling functions are accessible in closed form. The results show that slowly decorrelating observables detect persistently slow out-of-equilibrium dynamics, as opposed to intermittent behaviour punctuated by excursions into fast, effectively equilibrated states.

  20. Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease.

    PubMed

    van Diggelen, O P; Thobois, S; Tilikete, C; Zabot, M T; Keulemans, J L; van Bunderen, P A; Taschner, P E; Losekoot, M; Voznyi, Y V

    2001-08-01

    The fluorogenic enzyme assay for palmitoyl-protein thioesterase (PPT) has greatly facilitated the diagnosis of infantile neuronal ceroid lipofuscinosis (Santavuori-Haltia disease) and the search for possible new variants with atypical clinical presentation. Here, we present the first cases of adult neuronal ceroid lipofuscinosis with onset in the fourth decade of life due to a profound deficiency of PPT. The causative mutations in the CLN1 gene were the known, deleterious mutation R151X and the novel missense mutation G108R. Patients presented at onset (31 and 38 years), with psychiatric symptoms only. At present (ages 56 and 54 years), visual, verbal, and cognitive losses have progressed and both patients have cerebellar ataxia and cannot walk without support. PMID:11506414

  1. Natural history of adult-onset eIF2B-related disorders: a multi-centric survey of 16 cases.

    PubMed

    Labauge, Pierre; Horzinski, Laetitia; Ayrignac, Xavier; Blanc, Pierre; Vukusic, Sandra; Rodriguez, Diana; Mauguiere, Francois; Peter, Laure; Goizet, Cyril; Bouhour, Francoise; Denier, Christian; Confavreux, Christian; Obadia, Michael; Blanc, Frederic; de Sèze, Jérome; Fogli, Anne; Boespflug-Tanguy, Odile

    2009-08-01

    Mutations in one of the five eukaryotic initiation factor 2B genes (EIF2B1-5) were first described in childhood ataxia with cerebral hypomyelination--vanishing white matter syndrome. The syndrome is characterized by (i) cerebellar and pyramidal signs in children aged 2-5 years; (ii) extensive cavitating leucoencephalopathy; and (iii) episodes of rapid deterioration following stress. Since then a broad clinical spectrum from congenital to adult-onset forms has been reported, leading to the concept of eIF2B-related disorders. Our aim was to describe clinical and brain magnetic resonance imaging characteristics, genetic findings and natural history of patients with adult-onset eIF2B-related disorders (after age 16). The inclusion criteria were based on the presence of eIF2B mutations and a disease onset after the age of 16 years. One patient with an asymptomatic diagnosis (age 16 years) was also included. Clinical and magnetic resonance findings were retrospectively recorded in all patients. All patients were examined to assess clinical evolution, using functional, pyramidal, cerebellar and cognitive scales. This multi-centric study included 16 patients from 14 families. A sex ratio imbalance was noted (male/female = 3/13). The mean age of onset was 31.1 years (range 16-62). Initial symptoms were neurologic (n = 11), psychiatric (n = 2) and ovarian failure (n = 2). Onset of the symptoms was linked to a precipitating factor in 13% of cases that included minor head trauma and delivery. During follow-up (mean: 11.2 years, range 2-22 years) 12.5% of the patients died. Of the 14 survivors, 62% showed a decline in their cognitive functions, and 79% were severely handicapped or bedridden. One case remained asymptomatic. Stress worsened clinical symptoms in 38% of the patients. Magnetic resonance imaging findings consist of constant cerebral atrophy, extensive cystic leucoencephalopathy (81%), corpus callosum (69%) and cerebellar (38%) T2-weighted hyperintensities. All

  2. [A case in which the subject was affected by Listeia meningoencephalitis during administration of infliximab for steroid-dependent adult onset Still's disease].

    PubMed

    Yamamoto, Motohisa; Takahashi, Hiroki; Miyamoto, Chie; Ohara, Mikiko; Suzuki, Chisako; Naishiro, Yasuyoshi; Yamamoto, Hiroyuki; Shinomura, Yasuhisa; Nonaka, Michio; Imai, Kohzoh

    2006-06-01

    The subject was a 22-year-old woman who developed high fever and arthralgias and eruptions in the extremities around June 2005. She sought medical advice at a nearby dermatology clinic, where hepatic dysfunction was noted on blood testing. The patient was thus hospitalized the next day. Although CRP levels were significantly high, no sign of infection was observed and bone marrow cell differentiation was normal. Adult onset Still's disease was diagnosed based on the observation of persistent high fever >39 degrees C, eruptions, increased leukocytes, pharyngeal pain, splenomegaly, hepatic dysfunction, negative autoantibody results from blood testing, and high serum ferritin levels. Administration of prednisolone 30 mg/day was initiated, but proved ineffective. Steroid pulse therapy was conducted, and the subject was transferred to our medical facility for continued treatment. Attempts were made to control the disease using combined steroid and cyclosporine administration; but exacerbation of high serum ferritin levels and hepatic dysfunctions were observed, so a second course of steroid pulse therapy was conducted. Symptoms improved temporarily, but steroid levels were difficult to reduce. Cyclosporine was therefore replaced by methotrexate, and administration of infliximab was initiated. In the course of treatment, administration of a sulfamethoxazole/trimethoprim combination was initiated, but was discontinued due to suspicion of drug-induced hepatic injury. A second administration of infliximab was conducted in late August, and rapid improvements in clinical symptoms and abnormal test values was observed. However, high fever and headache developed suddenly in early September. Based on the results of spinal fluid testing, blood and spinal fluid cultures and MRI of the head, Listeria meningoencephalitis was diagnosed. Diplopia and impaired consciousness occurred during the disease course, and formation of a brain abscess was observed on imaging. However, symptoms

  3. Regular inhaled corticosteroids in adult-onset asthma and the risk for future cancer: a population-based cohort study with proper person-time analysis

    PubMed Central

    Kok, Victor C; Horng, Jorng-Tzong; Huang, Hsu-Kai; Chao, Tsung-Ming; Hong, Ya-Fang

    2015-01-01

    Background Recent studies have shown that inhaled corticosteroids (ICS) can exert anti-inflammatory effects for chronic airway diseases, and several observational studies suggest that they play a role as cancer chemopreventive agents, particularly against lung cancer. We aimed to examine whether regular ICS use was associated with a reduced risk for future malignancy in patients with newly diagnosed adult-onset asthma. Methods We used a population-based cohort study between 2001 and 2008 with appropriate person-time analysis. Participants were followed up until the first incident of cancer, death, or to the end of 2008. The Cox model was used to derive an adjusted hazard ratio (aHR) for cancer development. Kaplan–Meier cancer-free survival curves of two groups were compared. Results The exposed group of 2,117 regular ICS users and the nonexposed group of 17,732 non-ICS users were assembled. After 7,365 (mean, 3.5 years; standard deviation 2.1) and 73,789 (mean, 4.1 years; standard deviation 2.4) person-years of follow-up for the ICS users and the comparator group of non-ICS users, respectively, the aHR for overall cancer was nonsignificantly elevated at 1.33 with 95% confidence interval (CI), 1.00–1.76, P=0.0501. The Kaplan–Meier curves for overall cancer-free proportions of both groups were not significant (log-rank, P=0.065). Synergistic interaction of concurrent presence of regular ICS use was conducted using “ICS-negative and chronic obstructive pulmonary disease (COPD)-negative” as the reference. The aHR for the group of “ICS-positive, COPD-negative” did not reach statistically significant levels with aHR at 1.38 (95% CI, 0.53–3.56). There was a statistically significant synergistic interaction of concurrent presence of regular ICS use and COPD with aHR at 3.78 (95% CI, 2.10–6.81). Conclusion The protective effect of regular ICS use in the studied East Asian patients with adult-onset asthma was not detectable, contrary to reports of previous

  4. Synchronous states of slowly rotating pendula

    NASA Astrophysics Data System (ADS)

    Kapitaniak, Marcin; Czolczynski, Krzysztof; Perlikowski, Przemysław; Stefanski, Andrzej; Kapitaniak, Tomasz

    2014-08-01

    Coupled systems that contain rotating elements are typical in physical, biological and engineering applications and for years have been the subject of intensive studies. One problem of scientific interest, which among others occurs in such systems is the phenomenon of synchronization of different rotating parts. Despite different initial conditions, after a sufficiently long transient, the rotating parts move in the same way - complete synchronization, or a permanent constant shift is established between their displacements, i.e., the angles of rotation - phase synchronization. Synchronization occurs due to dependence of the periods of rotating elements motion and the displacement of the base on which these elements are mounted. We review the studies on the synchronization of rotating pendula and compare them with the results obtained for oscillating pendula. As an example we consider the dynamics of the system consisting of n pendula mounted on the movable beam. The pendula are excited by the external torques which are inversely proportional to the angular velocities of the pendula. As the result of such excitation each pendulum rotates around its axis of rotation. It has been assumed that all pendula rotate in the same direction or in the opposite directions. We consider the case of slowly rotating pendula and estimate the influence of the gravity on their motion. We classify the synchronous states of the identical pendula and observe how the parameters mismatch can influence them. We give evidence that synchronous states are robust as they exist in the wide range of system parameters and can be observed in a simple experiment.

  5. An autopsied case of adult-onset bulbospinalform Alexander disease with a novel S393R mutation in the GFAP gene.

    PubMed

    Iwasaki, Yasushi; Saito, Yufuko; Mori, Keiko; Ito, Masumi; Mimuro, Maya; Aiba, Ikuko; Saito, Kozo; Mizuta, Ikuko; Yoshida, Tomokatsu; Nakagawa, Masanori; Yoshida, Mari

    2015-01-01

    A 50-year-old Japanese man with no apparent family history noticed diplopia. He gradually showed gait disturbance and dysuria. Abducens disorder of eye movement with nystagmus, tongue atrophy with fasciculation, spastic tetraparesis, and sensory disturbance were also observed. MRI showed severe atrophy of the medulla oblongata to the cervical cord ("tadpole appearance"). Tracheotomy and gastrostomy were performed 7 years after onset due to the development of bulbar palsy. Death occurred following respiratory failure after 11 years total disease duration. The brain weighed 1,380 g. The cerebrum, cerebellum, midbrain, and upper pons were preserved from atrophy, but the medulla oblongata to the cervical cord showed severe atrophy. A few Rosenthal fibers were observed in the cerebral white matter, basal ganglia, and cerebellum, whereas numerous Rosenthal fibers were observed in the medulla oblongata to the cervical cord. Myelin loss with relatively preserved axons was extensively observed from the middle of the pons to the spinal cord. The clinicopathological diagnosis was adult-onset bulbospinal-form Alexander disease. Glial fibrillary acidic protein (GFAP) gene analysis revealed a novel mutation of S393R. Expression patterns of S393R mutant GFAP using adrenal carcinoma-derived cells (SW13 cells) showed a decreased number of filamentous structures and abnormal aggregates. PMID:25828773

  6. Iraqi oil industry slowly returning to normal

    SciTech Connect

    Not Available

    1992-09-07

    This paper reports that Iraq is making progress in putting its battered petroleum industry back together 1 1/2 years after the Persian Gulf war ended. OPEC News Agency (Opecna) reported the finish of reconstruction of Iraq's Mina al-Bakr oil terminal on the northern tip of the Persian Gulf, using Iraqi know-how and engineering personnel. The terminal, heavily damaged during the gulf conflict, has been restored to its prewar loading capacity of 1.6 million b/d at a cost of $16 million. Ninety per cent of the port had been damaged.

  7. In vivo and Ex vivo MR Imaging of Slowly Cycling Melanoma Cells

    PubMed Central

    Magnitsky, S.; Roesch, A.; Herlyn, M.; Glickson, J.D.

    2011-01-01

    Slowly cycling cells are believed to play a critical role in tumor progression and metastatic dissemination. The goal of this study was to develop a method for in vivo detection of slowly cycling cells. To distinguish these cells from more rapidly proliferating cells that constitute the vast majority of cells in tumors, we utilized the well-known effect of label dilution due to division of cells with normal cycle and retention of contrast agent in slowly dividing cells. To detect slowly cycling cells melanoma cells were labeled with iron oxide particles. After labeling, we observed dilution of contrast agent in parallel with cell proliferation in the vast majority of normally cycling cells. A small and distinct sub-population of iron-retaining cells was detected by flow cytometry after 20 days of in vitro proliferation. These iron-retaining cells exhibited high expression of a biological marker of slowly cycling cells, JARID1B. After implantation of labeled cells as xenografts into immunocompromised mice, iron-retaining cells were detected in vivo and ex vivo by MRI that was confirmed by Prussian Blue staining. MR imaging detects not only iron retaining melanoma cells but also iron positive macrophages. Proposed method opens up opportunities to image subpopulation of melanoma cells, which is critical for continuous tumor growth. PMID:21523820

  8. [Adult-onset rare diseases].

    PubMed

    Pfliegler, György; Kovács, Erzsébet; Kovács, György; Urbán, Krisztián; Nagy, Valéria; Brúgós, Boglárka

    2014-03-01

    The present paper is focusing on rare diseases manifesting in late childhood or adulthood. A part of these syndromes are not of genetic origin, such as relatively or absolutely rare infections, autoimmune diseases, tumours, or diseases due to rare environmental toxic agents. In addition, even a large proportion of genetic disorders may develop in adulthood or may have adult forms as well, affecting are almost each medical specialization. Examples are storage disorders (e.g. adult form of Tay-Sachs disease, Gaucher-disease), enzyme deficiencies (e.g. ornithin-transcarbamylase deficiency of the urea cycle disorders), rare thrombophilias (e.g. homozygous factor V. Leiden mutation, antithrombin deficiency), or some rare monogenic disorders such as Huntington-chorea and many others. It is now generally accepted that at least half of the 6-8000 "rare diseases" belong either to the scope of adult-care (e.g. internal medicine, neurology), or to "age-neutral" specialities such as ophtalmology, dermatology etc.). PMID:24566697

  9. Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region

    SciTech Connect

    Stoilova, D.; Trifan, O.C.; Sarfarazi, M.

    1996-08-15

    Primary open angle glaucoma (GLC1) is a common ocular disorder with a characteristic degeneration of the optic nerve and visual field defects that is often associated with an elevated intraocular pressure. The severe but rare juvenile-onset type has previously been mapped to 1q21-q31, and its genetic heterogeneity has been established. Herein, we present a new locus (GLC1B) for one form of GLC1 on chromosome 2cen-q13 with a clinical presentation of low to moderate intraocular pressure, onset in late 40s, and a good response to medical treatment. Two-point and haplotype analyses of affected and unaffected meioses in six families provided maximum linkage information with D2S417, GATA112EO3, D2S113, D2S373, and D2S274 (lod scores ranging from 3.11 to 6.48) within a region of 8.5 cM that is flanked by D2S2161 and D2S2264. Analysis of affected meioses alone revealed no recombination with an additional two markers (D2S2264 and D2S135) in a region of 11.2 cM that is flanked by D2S2161 and D2S176. Analysis of unaffected meioses identified only one healthy 86-year-old male who has inherited the entire affected haplotype and, hence, is a gene carrier for this condition. Eight additional families with similar and/or different clinical presentation did not show any linkage to this region and, therefore, provided evidence for genetic heterogeneity of adult-onset primary open angle glaucoma. 63 refs., 2 figs., 2 tabs.

  10. Functional and Structural Analyses of CYP1B1 Variants Linked to Congenital and Adult-Onset Glaucoma to Investigate the Molecular Basis of These Diseases.

    PubMed

    Banerjee, Antara; Chakraborty, Subhadip; Chakraborty, Abhijit; Chakrabarti, Saikat; Ray, Kunal

    2016-01-01

    Glaucoma, the leading cause of irreversible blindness, appears in various forms. Mutations in CYP1B1 result in primary congenital glaucoma (PCG) by an autosomal recessive mode of inheritance while it acts as a modifier locus for primary open angle glaucoma (POAG). We investigated the molecular basis of the variable phenotypes resulting from the defects in CYP1B1 by using subclones of 23 CYP1B1 mutants reported in glaucoma patients, in a cell based system by measuring the dual activity of the enzyme to metabolize both retinol and 17β-estradiol. Most variants linked to POAG showed low steroid metabolism while null or very high retinol metabolism was observed in variants identified in PCG. We examined the translational turnover rates of mutant proteins after the addition of cycloheximide and observed that the levels of enzyme activity mostly corroborated the translational turnover rate. We performed extensive normal mode analysis and molecular-dynamics-simulations-based structural analyses and observed significant variation of fluctuation in certain segmental parts of the mutant proteins, especially at the B-C and F-G loops, which were previously shown to affect the dynamic behavior and ligand entry/exit properties of the cytochrome P450 family of proteins. Our molecular study corroborates the structural analysis, and suggests that the pathologic state of the carrier of CYP1B1 mutations is determined by the allelic state of the gene. To our knowledge, this is the first attempt to dissect biological activities of CYP1B1 for correlation with congenital and adult onset glaucomas. PMID:27243976

  11. Echocardiographic assessment of subclinical left ventricular eccentric hypertrophy in adult-onset GHD patients by geometric remodeling: an observational case-control study

    PubMed Central

    de Gregorio, Cesare; Curtò, Lorenzo; Recupero, Antonino; Grimaldi, Patrizia; Almoto, Barbara; Venturino, Marilena; Cento, Domenico; Narbone, Maria Carola; Trimarchi, Francesco; Coglitore, Sebastiano; Cannavò, Salvatore

    2006-01-01

    Background Most patients with growth hormone deficiency (GHD) show high body mass index. Overweight subjects, but GHD patients, were demonstrated to have high left ventricular mass index (LVMi) and abnormal LV geometric remodeling. We sought to study these characteristics in a group of GHD patients, in an attempt to establish the BMI-independent role of GHD. Methods Fifty-four patients, 28 F and 26 M, aged 45.9 ± 13.1, with adult-onset GHD (pituitary adenomas 48.2%, empty sella 27.8%, pituitary inflammation 5.5%, cranio-pharyngioma 3.7%, not identified pathogenesis 14.8%) were enrolled. To minimize any possible interferences of BMI on the aim of this study, the control group included 20 age- and weight-matched healthy subjects. The LV geometry was identified by the relationship between LVMi (cut-off 125 g/m2) and relative wall thickness (cut-off 0.45) at echocardiography. Results There was no significant between-group difference in resting cardiac morphology and function, nor when considering age-related discrepancy. The majority of patients had normal-low LVM/LVMi, but about one fourth of them showed higher values. These findings correlated to relatively high circulating IGF-1 and systolic blood pressure at rest. The main LV geometric pattern was eccentric hypertrophy in 22% of GHD population (26% of with severe GHD) and in 15% of controls (p = NS). Conclusion Though the lack of significant differences in resting LV morphology and function, about 25% of GHD patients showed high LVMi (consisting of eccentric hypertrophy), not dissimilarly to overweight controls. This finding, which prognostic role is well known in obese and hypertensive patients, is worthy to be investigated in GHD patients through wider controlled trials. PMID:16507109

  12. Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia.

    PubMed

    Yasuda, T; Yamaguchi, N; Kobayashi, K; Nishi, I; Horinouchi, H; Jalil, M A; Li, M X; Ushikai, M; Iijima, M; Kondo, I; Saheki, T

    2000-12-01

    Adult-onset type II citrullinemia (CTLN2) is characterized by a liver-specific deficiency of argininosuccinate synthetase (ASS) protein. We have recently identified the gene responsible for CTLN2, viz., SLC25A13, which encodes a calcium-binding mitochondrial carrier protein, designated citrin, and found five mutations of the SLC25A13 gene in CTLN2 patients. In the present study, we have identified two novel mutations, 1800ins1 and R605X, in SLC25A13 mRNA and the SLC25A13 gene. Diagnostic analysis for the seven mutations in 103 CTLN2 patients diagnosed by biochemical and enzymatic studies has revealed that 102 patients had one or two of the seven mutations and 93 patients were homozygotes or compound heterozygotes. These results indicate that CTLN2 is caused by an abnormality in the SLC25A13 gene, and that our criteria for CTLN2 before DNA diagnosis are correct. Five of 22 patients from consanguineous unions have been shown to be compound heterozygotes, suggesting a high frequency of the mutated genes. The frequency of homozygotes is calculated to be more than 1 in 20,000 from carrier detection (6 in 400 individuals tested) in the Japanese population. We have detected no cross-reactive immune materials in the liver of CTLN2 patients with any of the seven mutations by Western blot analysis with anti-human citrin antibody. From these findings, we hypothesize that CTLN2 is caused by a complete deletion of citrin, although the mechanism of ASS deficiency is still unknown. PMID:11153906

  13. TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-Onset Still’s Disease and Their Association with Disease Activity and Clinical Manifestations

    PubMed Central

    Kim, Hyoun-Ah; Han, Jae Ho; Kim, Woo-Jung; Noh, Hyun Jin; An, Jeong-Mi; Yim, Hyunee; Jung, Ju-Yang; Kim, You-Sun; Suh, Chang-Hee

    2016-01-01

    S100A8/A9 has been suggested as a marker of disease activity in patients with adult-onset Still’s disease (AOSD). We evaluated the clinical significance of S100A8/A9 as a biomarker and its pathogenic role in AOSD. Blood samples were collected prospectively from 20 AOSD patients and 20 healthy controls (HCs). Furthermore, skin and lymph node biopsy specimens of AOSD patients were investigated for S100A8/A9 expression levels via immunohistochemistry. Peripheral blood mononuclear cells (PBMCs) of active AOSD patients and HCs were investigated for S100A8/A9 cell signals. S100A8/A9, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in active AOSD patients were higher than those of HCs. S100A8/A9 levels correlated positively with IL-1β, TNF-α and C-reactive protein. The inflammatory cells expressing S100A8/A9 were graded from one to three in skin and lymph node biopsies of AOSD patients. The grading for S100A8/A9 was more intense in the skin lesions with karyorrhexis, mucin deposition, and neutrophil infiltration. Like lipopolysaccharide (LPS), S100A8/A9 induced phosphorylation of p38 and c-Jun amino-terminal kinase (JNK) in PBMCs, suggesting that S100A8/A9 activates Toll-like receptor 4 signaling pathways. These findings suggest that S100A8/A9 may be involved in the inflammatory response with induction of proinflammatory cytokines and may serve as a clinicopathological marker for disease activity in AOSD. PMID:27537874

  14. Adult-Onset Deletion of β-Catenin in (10kb)Dmp1-Expressing Cells Prevents Intermittent PTH-Induced Bone Gain.

    PubMed

    Kedlaya, Rajendra; Kang, Kyung Shin; Hong, Jung Min; Bettagere, Vidya; Lim, Kyung-Eun; Horan, Daniel; Divieti-Pajevic, Paola; Robling, Alexander G

    2016-08-01

    β-Catenin (βcat) is a major downstream signaling node in canonical Wingless-related integration site (Wnt) signaling pathway, and its activity is crucial for canonical Wnt signal transduction. Wnt signaling has recently been implicated in the osteo-anabolic response to PTH, a potent calcium-regulating factor. We investigated whether βcat is essential for the anabolic action of intermittent PTH by generating male mice with adult-onset deletion of βcat in a subpopulation of bone cells (osteocytes and late-stage osteoblasts), treating them with an anabolic regimen of PTH, and measuring the skeletal responses. Male (10kb)Dmp1-CreERt2 transgenic mice that also harbored floxed loss-of-function βcat alleles (βcat(f/f)) were induced for Cre activity using tamoxifen, then injected daily with human PTH 1-34 (30 μg/kg) or vehicle for 5 weeks. Mice in which βcat was deleted showed either total lack of bone mineral density (BMD) gain, or BMD loss, and did not respond to PTH treatment. However, bone mass measurements in the trabecular compartment of the femur and spine revealed PTH-induced bone gain whether βcat was deleted or not. PTH-stimulated increases in periosteal and cancellous bone formation rates were not impaired by βcat deletion, but resorption markers and cortical porosity were significantly increased in induced mice, particularly induced mice treated with PTH. These results suggest that βcat is required for net-positive BMD effects of PTH therapy but that the anabolic effects per se of PTH treatment might not require osteocytic/osteoblastic βcat. PMID:27253995

  15. Elevated high-mobility group B1 levels in active adult-onset Still's disease associated with systemic score and skin rash.

    PubMed

    Jung, Ju-Yang; Suh, Chang-Hee; Sohn, Seonghyang; Nam, Jin-Young; Kim, Hyoun-Ah

    2016-08-01

    High-mobility group box-1 (HMGB1) is a nuclear protein, and such prototypical damage-associated molecular patterns mediate the immune response in the noninfectious inflammatory response. Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder involved in the dysregulation of innate immunity. We investigated the serum HMGB1 level in patients with AOSD and evaluated its clinical significance. Blood samples were collected from 40 patients with active AOSD and 40 healthy controls (HC). Of the patients with AOSD, follow-up samples were collected from 16 patients after a resolution of AOSD disease activity. Serum HMGB1 levels in patients with AOSD were higher than those of the HC (10.0 ± 5.85 vs. 5.15 ± 1.79 ng/mL, p < 0.001). Serum HMGB1 levels were found to be correlated with C-reactive protein (CRP) and the systemic score. The AOSD patient who had a sore throat showed a higher serum HMGB1 level than those patients who did not, and the patient with a skin rash had higher levels than the patients without. In addition, the serum HMGB1 levels were decreased after the resolution of disease activity in the AOSD patients who were followed up. The serum HMGB1 levels were elevated in AOSD patients compared to the HC and were correlated with both CRP and the systemic score. The HMGB1 levels were associated with skin rash and a sore throat in AOSD patients. After the resolution of disease activity, serum HMGB1 levels were found to have decreased. PMID:27225247

  16. Functional and Structural Analyses of CYP1B1 Variants Linked to Congenital and Adult-Onset Glaucoma to Investigate the Molecular Basis of These Diseases

    PubMed Central

    Chakrabarti, Saikat; Ray, Kunal

    2016-01-01

    Glaucoma, the leading cause of irreversible blindness, appears in various forms. Mutations in CYP1B1 result in primary congenital glaucoma (PCG) by an autosomal recessive mode of inheritance while it acts as a modifier locus for primary open angle glaucoma (POAG). We investigated the molecular basis of the variable phenotypes resulting from the defects in CYP1B1 by using subclones of 23 CYP1B1 mutants reported in glaucoma patients, in a cell based system by measuring the dual activity of the enzyme to metabolize both retinol and 17β-estradiol. Most variants linked to POAG showed low steroid metabolism while null or very high retinol metabolism was observed in variants identified in PCG. We examined the translational turnover rates of mutant proteins after the addition of cycloheximide and observed that the levels of enzyme activity mostly corroborated the translational turnover rate. We performed extensive normal mode analysis and molecular-dynamics-simulations-based structural analyses and observed significant variation of fluctuation in certain segmental parts of the mutant proteins, especially at the B-C and F-G loops, which were previously shown to affect the dynamic behavior and ligand entry/exit properties of the cytochrome P450 family of proteins. Our molecular study corroborates the structural analysis, and suggests that the pathologic state of the carrier of CYP1B1 mutations is determined by the allelic state of the gene. To our knowledge, this is the first attempt to dissect biological activities of CYP1B1 for correlation with congenital and adult onset glaucomas. PMID:27243976

  17. Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP).

    PubMed

    Chitu, Violeta; Gokhan, Solen; Gulinello, Maria; Branch, Craig A; Patil, Madhuvati; Basu, Ranu; Stoddart, Corrina; Mehler, Mark F; Stanley, E Richard

    2015-02-01

    Mutations in the colony stimulating factor-1 receptor (CSF1R) that abrogate the expression of the affected allele or lead to the expression of mutant receptor chains devoid of kinase activity have been identified in both familial and sporadic cases of ALSP. To determine the validity of the Csf1r heterozygous mouse as a model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) we performed behavioral, radiologic, histopathologic, ultrastructural and cytokine expression studies of young and old Csf1r+/- and control Csf1r+/+ mice. Six to 8-month old Csf1r+/- mice exhibit cognitive deficits, and by 9-11 months develop sensorimotor deficits and in male mice, depression and anxiety-like behavior. MRIs of one year-old Csf1r+/- mice reveal lateral ventricle enlargement and thinning of the corpus callosum. Ultrastructural analysis of the corpus callosum uncovers dysmyelinated axons as well as neurodegeneration, evidenced by the presence of axonal spheroids. Histopathological examination of 11-week-old mice reveals increased axonal and myelin staining in the cortex, increase of neuronal cell density in layer V and increase of microglial cell densities throughout the brain, suggesting that early developmental changes contribute to disease. By 10-months of age, the neuronal cell density normalizes, oligodendrocyte precursor cells increase in layers II-III and V and microglial densities remain elevated without an increase in astrocytes. Also, the age-dependent increase in CSF-1R+ neurons in cortical layer V is reduced. Moreover, the expression of Csf2, Csf3, Il27 and Il6 family cytokines is increased, consistent with microglia-mediated inflammation. These results demonstrate that the inactivation of one Csf1r allele is sufficient to cause an ALSP-like disease in mice. The Csf1r+/- mouse is a model of ALSP that will allow the critical events for disease development to be determined and permit rapid evaluation of therapeutic approaches. Furthermore

  18. Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP)

    PubMed Central

    Chitu, Violeta; Gokhan, Solen; Gulinello, Maria; Branch, Craig A.; Patil, Madhuvati; Basu, Ranu; Stoddart, Corrina; Mehler, Mark F.; Stanley, E. Richard

    2014-01-01

    Mutations in the colony stimulating factor-1 receptor (CSF1R) that abrogate the expression of the affected allele or lead to the expression of mutant receptor chains devoid of kinase activity have been identified in both familial and sporadic cases of ALSP. To determine the validity of the Csf1r heterozygous mouse as a model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) we performed behavioral, radiologic, histopathologic, ultrastructural and cytokine expression studies of young and old Csf1r+/− and control Csf1r+/+ mice. Six to 8-month old Csf1r+/− mice exhibit cognitive deficits, and by 9-11 months develop sensorimotor deficits and in male mice, depression and anxiety-like behavior. MRIs of one year-old Csf1r+/− mice reveal lateral ventricle enlargement and thinning of the corpus callosum. Ultrastructural analysis of the corpus callosum uncovers dysmyelinated axons as well as neurodegeneration, evidenced by the presence of axonal spheroids. Histopathological examination of 11-week-old mice reveals increased axonal and myelin staining in the cortex, increase of neuronal cell density in layer V and increase of microglial cell densities throughout the brain, suggesting that early developmental changes contribute to disease. By 10-months of age, the neuronal cell density normalizes, oligodendrocyte precursor cells increase in layers II-III and V and microglial densities remain elevated without an increase in astrocytes. Also, the age-dependent increase in CSF-1R+ neurons in cortical layer V is reduced. Moreover, the expression of Csf2, Csf3, Il27 and Il6 family cytokines is increased, consistent with microglia-mediated inflammation. These results demonstrate that the inactivation of one Csf1r allele is sufficient to cause an ALSP-like disease in mice. The Csf1r+/− mouse is a model of ALSP that will allow the critical events for disease development to be determined and permit rapid evaluation of therapeutic approaches

  19. Radiative transitions of excited ions moving slowly in plasmas

    SciTech Connect

    Hu, Hongwei Chen, Wencong; Li, Peng; Zhao, Yongtao; Zhou, Xianming; Li, Zhen; Li, Fuli; Dong, Chenzhong

    2014-12-15

    The electric dipole transitions of excited ions moving slowly in plasmas are studied. The results show that some transitions forbidden for excited ions at rest become allowed for moving excited ions. The transition rates change with varying speed of the ions. Forbidden transitions are strongly influenced by the speed, non-forbidden transitions are weakly influenced.

  20. Slow Sodium: An Oral Slowly Released Sodium Chloride Preparation

    PubMed Central

    Clarkson, E. M.; Curtis, J. R.; Jewkes, R. J.; Jones, B. E.; Luck, V. A.; de Wardener, H. E.; Phillips, N.

    1971-01-01

    The use of a slowly released oral preparation of sodium chloride is described. It was given to patients and athletes to treat or prevent acute and chronic sodium chloride deficiency. Gastrointestinal side effects were not encountered after the ingestion of up to 500 mEq in one day or 200 mEq in 10 minutes. PMID:5569979

  1. AUTOMATED MALLEABLE ANNEALING OVENS SLOWLY HEAT AND COOL CASTINGS AS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    AUTOMATED MALLEABLE ANNEALING OVENS SLOWLY HEAT AND COOL CASTINGS AS THEY MOVE IN BINS ALONG TRACKS IN THE OVEN BOTTOM IN THE MALLEABLE ANNEALING BUILDING. THIS PROCESS TRANSFORMS BRITTLE WHITE IRON CASTINGS INTO SOFTER, STRONGER MALLEABLE IRON. - Stockham Pipe & Fittings Company, Malleable Annealing Building, 4000 Tenth Avenue North, Birmingham, Jefferson County, AL

  2. Slow sodium: an oral slowly released sodium chloride preparation.

    PubMed

    Clarkson, E M; Curtis, J R; Jewkes, R J; Jones, B E; Luck, V A; de Wardener, H E; Phillips, N

    1971-09-11

    The use of a slowly released oral preparation of sodium chloride is described. It was given to patients and athletes to treat or prevent acute and chronic sodium chloride deficiency. Gastrointestinal side effects were not encountered after the ingestion of up to 500 mEq in one day or 200 mEq in 10 minutes. PMID:5569979

  3. Molecular basis of adult-onset and chronic G sub M2 gangliosidoses in patients of Ashkenazi Jewish origin: Substitution of serine for glycine at position 269 of the. alpha. -subunit of. beta. -hexosaminidase

    SciTech Connect

    Paw, B.H.; Kaback, M.M.; Neufeld, E.F. )

    1989-04-01

    Chronic and adult-onset G{sub M2} gangliosidoses are neurological disorders caused by marked deficiency of the A isoenzyme of {beta}-hexosaminidase; they occur in the Ashkenazi Jewish population, though less frequently than classic (infantile) Tay-Sachs disease. Earlier biosynthetic studies had identified a defective {alpha}-subunit that failed to associate with the {beta}-subunit. The authors have now found a guanosine to adenosine transition at the 3{prime} end of exon 7, which causes substitution of serine for glycine at position 269 of the {alpha}-subunit. An RNase protection assay was used to localize the mutation to a segment of mRNA from fibroblasts of a patient with the adult-onset disorder. That segment of mRNA (after reverse transcription) and a corresponding segment of genomic DNA were amplified by the polymerase chain reaction and sequenced by the dideoxy method. The sequence analysis, together with an assay based on the loss of a ScrFI restriction site, showed that the patient was a compound heterozygote who had inherited the 269 (Gly {yields} Ser) mutation from his father and an allelic null mutation from his mother. The 269 (Gly {yields} Ser) mutation, in compound heterozygosity with a presumed null allele, was also found in fetal fibroblasts with an association-defective phenotype and in cells from five patients with chronic G{sub M2} gangliosidosis.

  4. Biallelic CACNA1A mutations cause early onset epileptic encephalopathy with progressive cerebral, cerebellar, and optic nerve atrophy.

    PubMed

    Reinson, Karit; Õiglane-Shlik, Eve; Talvik, Inga; Vaher, Ulvi; Õunapuu, Anne; Ennok, Margus; Teek, Rita; Pajusalu, Sander; Murumets, Ülle; Tomberg, Tiiu; Puusepp, Sanna; Piirsoo, Andres; Reimand, Tiia; Õunap, Katrin

    2016-08-01

    The CACNA1A gene encodes the transmembrane pore-forming alpha-1A subunit of the Cav 2.1 P/Q-type voltage-gated calcium channel. Several heterozygous mutations within this gene, including nonsense mutations, missense mutations, and expansion of cytosine-adenine-guanine repeats, are known to cause three allelic autosomal dominant conditions-episodic ataxia type 2, familial hemiplegic migraine type 1, and spinocerebellar ataxia type 6. An association with epilepsy and CACNA1A mutations has also been described. However, the link with epileptic encephalopathies has emerged only recently. Here we describe two patients, sister and brother, with compound heterozygous mutations in CACNA1A. Exome sequencing detected biallelic mutations in CACNA1A: A missense mutation c.4315T>A (p.Trp1439Arg) in exon 27, and a seven base pair deletion c.472_478delGCCTTCC (p.Ala158Thrfs*6) in exon 3. Both patients were normal at birth, but developed daily recurrent seizures in early infancy with concomitant extreme muscular hypotonia, hypokinesia, and global developmental delay. The brain MRI images showed progressive cerebral, cerebellar, and optic nerve atrophy. At the age of 5, both patients were blind and bedridden with a profound developmental delay. The elder sister died at that age. Their parents and two siblings were heterozygotes for one of those pathogenic mutations and expressed a milder phenotype. Both of them have intellectual disability and in addition the mother has adult onset cerebellar ataxia with a slowly progressive cerebellar atrophy. Compound heterozygous mutations in the CACNA1A gene presumably cause early onset epileptic encephalopathy, and progressive cerebral, cerebellar and optic nerve atrophy with reduced lifespan. © 2016 Wiley Periodicals, Inc. PMID:27250579

  5. Slowly Growing Nodule on the Trunk: Cutaneous Granular Cell Tumor

    PubMed Central

    Gündüz, Özge; Erkin, Gül; Bilezikçi, Banu; Adanalı, Gökhan

    2016-01-01

    Granular cell tumor (GCT) is a rare benign neoplasm of the skin that accounts for 0.5% of all soft-tissue tumors. The tumor mostly presents with a symptomatic slowly growing solitary nodule and overlying normal skin; therefore, it is not always considered in the differential diagnosis. Here, we report a 58-year-old female patient who presented with a 4-year history of a slowly growing mass, with a dimension of 5 × 4 cm on her left waist, diagnosed as a GCT at the histopathological examination. The neoplastic cells had centrally located nuclei and granular eosinophilic cytoplasm and stained positively for S100, neuron-specific enolase, and CD68 antibodies. Fifteen months after surgery, the patient still showed no signs of local recurrence or metastases. Although a large diameter is a feature of malignant GCT, our case with cutaneous GCT was localized on the trunk and did not present malignant features clinically and histopathologically.

  6. Slowly rotating fluid balls of Petrov type D

    SciTech Connect

    Bradley, Michael; Eriksson, Daniel; Fodor, Gyula; Racz, Istvan

    2007-01-15

    The second order perturbative field equations for slowly and rigidly rotating perfect fluid balls of Petrov type D are solved numerically. It is found that all the slowly and rigidly rotating perfect fluid balls up to second order, irrespective of Petrov type, may be matched to a possibly nonasymptotically flat stationary axisymmetric vacuum exterior. The Petrov type D interior solutions are characterized by five integration constants, corresponding to density and pressure of the zeroth order configuration, the magnitude of the vorticity, one more second order constant, and an independent spherically symmetric second order small perturbation of the central pressure. A four-dimensional subspace of this five-dimensional parameter space is identified for which the solutions can be matched to an asymptotically flat exterior vacuum region. Hence these solutions are completely determined by the spherical configuration and the magnitude of the vorticity. The physical properties, like equation of state, shape, and speed of sound, are determined for a number of solutions.

  7. Tidal deformation of a slowly rotating material body: External metric

    NASA Astrophysics Data System (ADS)

    Landry, Philippe; Poisson, Eric

    2015-05-01

    We construct the external metric of a slowly rotating, tidally deformed material body in general relativity. The tidal forces acting on the body are assumed to be weak and to vary slowly with time, and the metric is obtained as a perturbation of a background metric that describes the external geometry of an isolated, slowly rotating body. The tidal environment is generic and characterized by two symmetric trace-free tidal moments Ea b and Ba b, and the body is characterized by its mass M , its radius R , and a dimensionless angular-momentum vector χa≪1 . The perturbation accounts for all couplings between χa and the tidal moments. The body's gravitational response to the applied tidal field is measured in part by the familiar gravitational Love numbers K2el and K2mag , but we find that the coupling between the body's rotation and the tidal environment requires the introduction of four new quantities, which we designate as rotational-tidal Love numbers. All these Love numbers are gauge invariant in the usual sense of perturbation theory, and all vanish when the body is a black hole.

  8. An atypical presentation of adult-onset Still’s disease complicated by pulmonary hypertension and macrophage activation syndrome treated with immunosuppression: a case-based review of the literature

    PubMed Central

    Manson, Daniel K.; Horn, Evelyn M.; Haythe, Jennifer

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a known complication of rheumatologic diseases, but it is only rarely associated with adult-onset Still’s disease (AOSD). We describe the case of a 30-year-old woman who presented in a pulmonary hypertension crisis and was found to have underlying AOSD with PAH and nonspecific interstitial pneumonia (NSIP) with a course complicated by macrophage activation syndrome (MAS). She dramatically improved with steroids, cyclosporine A, and anakinra, with total resolution of the MAS and significant improvement of her pulmonary arterial pressures. While there are only select case reports of AOSD associated with PAH, this is the first reported case of (1) AOSD complicated by both PAH and MAS and (2) AOSD complicated by biopsy-proven NSIP. Clinically, this case highlights the efficacy of immunosuppressive agents in the treatment of PAH and MAS from underlying AOSD and supports their use in this setting. PMID:27162622

  9. Slowly rotating black holes with nonlinear electrodynamics in five dimensions

    NASA Astrophysics Data System (ADS)

    Hendi, S. H.; Sepehri Rad, M.

    2014-10-01

    Employing linear order perturbation theory with the rotation parameter as the perturbative parameter, we obtain asymptotically AdS slowly rotating black hole solutions in the Einstein gravity with Born-Infeld (BI) type nonlinear electrodynamics (NED). We start from asymptotically AdS static black hole solutions coupled to BI type NED in five dimensions. Then, we consider the effect of adding a small amount of angular momenta to the seed solutions. Finally, we investigate the geometry and thermodynamic properties of the solutions.

  10. Bending of solitons in weak and slowly varying inhomogeneous plasma

    SciTech Connect

    Mukherjee, Abhik Janaki, M. S. Kundu, Anjan

    2015-12-15

    The bending of solitons in two dimensional plane is presented in the presence of weak and slowly varying inhomogeneous ion density for the propagation of ion acoustic soliton in unmagnetized cold plasma with isothermal electrons. Using reductive perturbation technique, a modified Kadomtsev-Petviashvili equation is obtained with a chosen unperturbed ion density profile. The exact solution of the equation shows that the phase of the solitary wave gets modified by a function related to the unperturbed inhomogeneous ion density causing the soliton to bend in the two dimensional plane, while the amplitude of the soliton remains constant.

  11. Dynamic control for nanostructures through slowly ramping parameters

    NASA Astrophysics Data System (ADS)

    Yoo, Jaeyun; Blick, Robert; Ahn, Kang-Hun

    2016-06-01

    We propose a nanostructure control method which uses slowly ramping parameters. We demonstrate the dynamics of this method in both a nonlinear classical system and a quantum system. When a quantum mechanical two-level atom (quantum dot) is irradiated by an electric field with a slowly increasing frequency, there exists a sudden transition from ground (excited) to excited (ground) state. This occurs when the ramping rate is smaller than the square of the Rabi frequency. The transition arises when its "instant frequency"—the time derivative of the driving field phase—matches the resonance frequency, satisfying the Fermi golden rule. We also find that the parameter ramping is an efficient control manner for classical nanomechanical shuttles. For ramping of driving amplitudes, the shuttle's mechanical oscillation is amplified and even survives when the ramping is stopped outside the original oscillation region. This strange oscillation is due to the entrance into a multistable dynamic region in phase space. For ramping of driving frequencies, an onset of oscillation arises when the instant frequency enters the oscillation region. Thus, regardless of being classical or quantum, the instant frequency is physically relevant. We discuss in which conditions the dynamic control is efficient.

  12. External Electromagnetic Fields of Slowly Rotating Relativistic Magnetized NUT Stars

    NASA Astrophysics Data System (ADS)

    Ahmedov, B. J.; Khugaev, A. V.

    2006-08-01

    Analytic general relativistic expressions for the electromagnetic fields external to a slowly-rotating magnetized NUT star with non-vanishing gravitomagnetic charge have been presented. Solutions for the electric and magnetic fields have been found after separating the Maxwell equations in the external background spacetime of a slowly rotating NUT star into angular and radial parts in the lowest order approximation in specific angular momentum and NUT parameter . The relativistic star is considered isolated and in vacuum, with different models for stellar magnetic field: i) monopolar magnetic field and ii) dipolar magnetic field aligned with the axis of rotation. It has been shown that the general relativistic corrections due to the dragging of reference frames and gravitomagnetic charge are not present in the form of the magnetic fields but emerge only in the form of the electric fields. In particular, it has been obtained that the frame-dragging and gravitomagnetic charge provide an additional induced electric field which is analogous to the one introduced by the rotation of the star in the flat spacetime limit.

  13. A slowly evolving host moves first in symbiotic interactions

    NASA Astrophysics Data System (ADS)

    Damore, James; Gore, Jeff

    2011-03-01

    Symbiotic relationships, both parasitic and mutualistic, are ubiquitous in nature. Understanding how these symbioses evolve, from bacteria and their phages to humans and our gut microflora, is crucial in understanding how life operates. Often, symbioses consist of a slowly evolving host species with each host only interacting with its own sub-population of symbionts. The Red Queen hypothesis describes coevolutionary relationships as constant arms races with each species rushing to evolve an advantage over the other, suggesting that faster evolution is favored. Here, we use a simple game theoretic model of host- symbiont coevolution that includes population structure to show that if the symbionts evolve much faster than the host, the equilibrium distribution is the same as it would be if it were a sequential game where the host moves first against its symbionts. For the slowly evolving host, this will prove to be advantageous in mutualisms and a handicap in antagonisms. The model allows for symbiont adaptation to its host, a result that is robust to changes in the parameters and generalizes to continuous and multiplayer games. Our findings provide insight into a wide range of symbiotic phenomena and help to unify the field of coevolutionary theory.

  14. Slowly rotating black holes in Einstein-æther theory

    NASA Astrophysics Data System (ADS)

    Barausse, Enrico; Sotiriou, Thomas P.; Vega, Ian

    2016-02-01

    We study slowly rotating, asymptotically flat black holes in Einstein-æther theory and show that solutions that are free from naked finite area singularities form a two-parameter family. These parameters can be thought of as the mass and angular momentum of the black hole, while there are no independent æ ther charges. We also show that the æ ther has nonvanishing vorticity throughout the spacetime, as a result of which there is no hypersurface that resembles the universal horizon found in static, spherically symmetric solutions. Moreover, for experimentally viable choices of the coupling constants, the frame-dragging potential of our solutions only shows percent-level deviations from the corresponding quantities in General Relativity and Hořava gravity. Finally, we uncover and discuss several subtleties in the correspondence between Einstein-æther theory and Hořava gravity solutions in the cω→∞ limit.

  15. Periodic attitude control of a slowly spinning spacecraft.

    NASA Technical Reports Server (NTRS)

    Todosiev, E. P.

    1973-01-01

    A periodic attitude control system is presented which permits control of secular errors of a slowly spinning spacecraft operating in a high disturbance environment. Attitude errors of the spin-axis are detected by sun sensors (or rate gyros) and are controlled by a periodic control law which modulates external control torques generated by mass expulsion torquers. Attitude stability during the uncontrolled periods is obtained passively via the vehicle spin momentum. Equations of motion, a system block diagram, and design parameters are presented for a typical spacecraft application. Simulation results are included which demonstrate the feasibility of the novel control concept. Salient features of the periodic control approach are implementation simplicity, excellent response, and a propellant utilization efficiency greater than 75 percent.

  16. NEW SCALING FOR THE ALPHA EFFECT IN SLOWLY ROTATING TURBULENCE

    SciTech Connect

    Brandenburg, A.; Gressel, O.; Kaepylae, P. J.; Kleeorin, N.; Rogachevskii, I.; Mantere, M. J.

    2013-01-10

    Using simulations of slowly rotating stratified turbulence, we show that the {alpha} effect responsible for the generation of astrophysical magnetic fields is proportional to the logarithmic gradient of kinetic energy density rather than that of momentum, as was previously thought. This result is in agreement with a new analytic theory developed in this paper for large Reynolds numbers and slow rotation. Thus, the contribution of density stratification is less important than that of turbulent velocity. The {alpha} effect and other turbulent transport coefficients are determined by means of the test-field method. In addition to forced turbulence, we also investigate supernova-driven turbulence and stellar convection. In some cases (intermediate rotation rate for forced turbulence, convection with intermediate temperature stratification, and supernova-driven turbulence), we find that the contribution of density stratification might be even less important than suggested by the analytic theory.

  17. The strange flight behaviour of slowly spinning soccer balls

    NASA Astrophysics Data System (ADS)

    Mizota, Taketo; Kurogi, Kouhei; Ohya, Yuji; Okajima, Atsushi; Naruo, Takeshi; Kawamura, Yoshiyuki

    2013-05-01

    The strange three-dimensional flight behaviour of slowly spinning soccer balls is one of the most interesting and unknown phenomenon associated with the trajectories of sports balls. Many spectators have experienced numerous exciting and emotional instances while observing the curious flight behaviour of these balls. We examine the aerodynamic mechanisms of erratic ball behaviours through real flight observations, unsteady force measurements and flow pattern visualisations. The strange behaviour is elucidated by the relationship between the unsteady forces on the ball and the wake flow. The irregular changes in position for twin longitudinal vortices have already been discovered in the supercritical Reynolds number region of a sphere with a smooth surface. This finding is applicable to the strange behaviour of the flight of soccer balls with this supercritical flow. The players, spectators, and television viewers will gain greater insight into the effects of soccer ball flights.

  18. Search for slowly moving magnetic monopoles with the MACRO detector

    SciTech Connect

    Ahlen, S.; Ambrosio, M.; Antolini, R.; Auriemma, G.; Baker, R.; Baldini, A.; Bam, B.B.; Barbarino, G.C.; Barish, B.C.; Battistoni, G.; Bellotti, R.; Bemporad, C.; Bernandini, P.; Bilokon, H.; Bisi, V.; Bloise, C.; Bower, C.; Bussino, S.; Cafagna, F.; Calicchio, M.; Campana, D.; Campana, P.; Carboni, M.; Cecchini, S.; Cei, F.; Chiarella, V.; Cormack, R.; Corona, A.; Coutu, S.; De Cataldo, G.; Dekhissi, H.; De Marzo, C.; De Vincenzi, M.; Di Credico, A.; Diehl, E.; Erriquez, O.; Favuzzi, C.; Ficenec, D.; Forti, C.; Fusco, P.; Giacomelli, G.; Giannini, G.; Giglietto, N.; Giubellino, P.; Grassi, M.; Green, P.; Grillo, A.; Guarino, F.; Guarnaccia, P.; Gustavino, C.; Habig, A.; Heinz, R.; Hong, J.T.; Iarocci, E.; Katsavounidis, E.; Kearns, E.; Klein, S.; Kyriazopoulou, S.; Lamanna, E.; Lane, C.; Lee, C.; Levin, D.; Lipari, P.; Liu, G.; Liu, R.; Longo, M.J.; Lu, Y.; Ludlam, G.; Mancarella, G.; Mandrioli, G.; Margiotta-Neri, A.; Marin, A.; Marini, A.; Martello, D.; Marzari Chiesa, A.; Masera, M

    1994-01-31

    A search for slowly moving magnetic monopoles in the cosmic radiation was conducted from October 1989 to November 1991 using the large liquid scintillator detector subsystem of the first supermodule of the MACRO detector at the Gran Sasso underground laboratory. The absence of candidates established an upper limit on the monopole flux of 5.6[times]10[sup [minus]15] cm[sup [minus]2] sr[sup [minus]1] s[sup [minus]1] at 90% confidence level in the velocity range of 10[sup [minus]4][approx lt][beta][lt]4[times]10[sup [minus]3]. This result places a new constraint on the abundance of monopoles trapped in our solar system.

  19. Slowly rotating black holes in alternative theories of gravity

    SciTech Connect

    Pani, Paolo; Macedo, Caio F. B.; Crispino, Luis C. B.; Cardoso, Vitor

    2011-10-15

    We present, in closed analytic form, a general stationary, slowly rotating black hole, which is a solution to a large class of alternative theories of gravity in four dimensions. In these theories, the Einstein-Hilbert action is supplemented by all possible quadratic, algebraic curvature invariants coupled to a scalar field. The solution is found as a deformation of the Schwarzschild metric in general relativity. We explicitly derive the changes to the orbital frequency at the innermost stable circular orbit and at the light ring in closed form. These results could be useful when comparing general relativity against alternative theories by (say) measurements of x-ray emission in accretion disks, or by stellar motion around supermassive black holes. When gravitational-wave astronomy comes into force, strong constraints on the coupling parameters can in principle be made.

  20. Calculation of trajectories using constant and slowly varying functions

    NASA Technical Reports Server (NTRS)

    Culpepper, B. K.

    1971-01-01

    A method is presented for calculating trajectories for the restricted problem of three bodies which utilizes conic propagation of the state vector with frequency correction of position and velocity by means of a constant or slowly varying function. This method of calculating trajectories was applied to the planar circular restricted three body problem, the planar elliptic restricted problem, and the ephemeral restricted problem. Two methods (the refined method and the straight forward method) of determining the direction of the position correction are presented for the circular restricted problem and the elliptic restricted problem of three bodies. Only the straight forward method was used with the ephemeral restricted problem. The earth, the moon, and a space vehicle comprise the restricted three body model that is used.

  1. The strange flight behaviour of slowly spinning soccer balls

    PubMed Central

    Mizota, Taketo; Kurogi, Kouhei; Ohya, Yuji; Okajima, Atsushi; Naruo, Takeshi; Kawamura, Yoshiyuki

    2013-01-01

    The strange three-dimensional flight behaviour of slowly spinning soccer balls is one of the most interesting and unknown phenomenon associated with the trajectories of sports balls. Many spectators have experienced numerous exciting and emotional instances while observing the curious flight behaviour of these balls. We examine the aerodynamic mechanisms of erratic ball behaviours through real flight observations, unsteady force measurements and flow pattern visualisations. The strange behaviour is elucidated by the relationship between the unsteady forces on the ball and the wake flow. The irregular changes in position for twin longitudinal vortices have already been discovered in the supercritical Reynolds number region of a sphere with a smooth surface. This finding is applicable to the strange behaviour of the flight of soccer balls with this supercritical flow. The players, spectators, and television viewers will gain greater insight into the effects of soccer ball flights. PMID:23695000

  2. Slowly Varying Dilaton Cosmologies and Their Field Theory Duals

    SciTech Connect

    Awad, Adel; Das, Sumit R.; Ghosh, Archisman; Oh, Jae-Hyuk; Trivedi, Sandip P.; /Tata Inst. /Stanford U., ITP /SLAC

    2011-06-28

    We consider a deformation of the AdS{sub 5} x S{sup 5} solution of IIB supergravity obtained by taking the boundary value of the dilaton to be time dependent. The time dependence is taken to be slowly varying on the AdS scale thereby introducing a small parameter {epsilon}. The boundary dilaton has a profile which asymptotes to a constant in the far past and future and attains a minimum value at intermediate times. We construct the sugra solution to first non-trivial order in {epsilon}, and find that it is smooth, horizon free, and asymptotically AdS{sub 5} x S{sup 5} in the far future. When the intermediate values of the dilaton becomes small enough the curvature becomes of order the string scale and the sugra approximation breaks down. The resulting dynamics is analysed in the dual SU(N) gauge theory on S{sup 3} with a time dependent coupling constant which varies slowly. When N{epsilon} << 1, we find that a quantum adiabatic approximation is applicable, and use it to argue that at late times the geometry becomes smooth AdS{sub 5} x S{sup 5} again. When N{epsilon} >> 1, we formulate a classical adiabatic perturbation theory based on coherent states which arises in the large N limit. For large values of the tHooft coupling this reproduces the supergravity results. For small 'tHooft coupling the coherent state calculations become involved and we cannot reach a definite conclusion. We argue that the final state should have a dual description which is mostly smooth AdS5 space with the possible presence of a small black hole.

  3. The role of sea ice in slowly rotating aquaplanet simulations

    NASA Astrophysics Data System (ADS)

    Salameh, Josiane; Popp, Max; Marotzke, Jochem

    2016-04-01

    A large fraction of recently discovered exoplanets are found in close orbit from their star. Their rotation period is expected to be slow due to important tidal forces. Therefore, in order to assess the habitability of slowly rotating planets, it is imperative to understand how slow rotation periods affect the climate. Under different Earth-like configurations, previous studies focused on the special case of synchronous rotation where the orbital and planetary rotation periods are identical. In addition, simulations with non-synchronous rotations did not account for sea ice. Therefore, we turn on the thermodynamics sea-ice model in the state-of-the-art atmospheric general circulation model ECHAM6 coupled to a mixed-layer ocean and investigate the aquaplanet's climate across rotation periods between one and 365 Earth days. Simulations with the sea-ice model turned on show a global-mean surface temperature up to 25 K lower than simulations with the sea-ice model turned off, particularly for rotation periods between 64 and 300 days. For both type of experiments, the climate cools with increasing rotation period. However, when sea ice is included, the significant drop in the global-mean surface temperature is due to sea-ice reaching low latitudes. Then, beyond a 200 days rotation period, sea ice grows over the equatorial region during the nighttime and persists well into the daytime. This causes a high contribution of the sea-ice albedo to the planetary albedo. Our study illustrates, thus, that sea-ice plays a crucial role in shaping the climate on slowly rotating planets.

  4. Slowly varying dilaton cosmologies and their field theory duals

    SciTech Connect

    Awad, Adel; Das, Sumit R.; Ghosh, Archisman; Oh, Jae-Hyuk; Trivedi, Sandip P.

    2009-12-15

    We consider a deformation of the AdS{sub 5}xS{sup 5} solution of IIB supergravity obtained by taking the boundary value of the dilaton to be time dependent. The time dependence is taken to be slowly varying on the anti-de Sitter (AdS) scale thereby introducing a small parameter {epsilon}. The boundary dilaton has a profile which asymptotes to a constant in the far past and future and attains a minimum value at intermediate times. We construct the supergravity (sugra) solution to first nontrivial order in {epsilon}, and find that it is smooth, horizon-free, and asymptotically AdS{sub 5}xS{sup 5} in the far future. When the intermediate values of the dilaton becomes small enough the curvature becomes of order the string scale and the sugra approximation breaks down. The resulting dynamics is analyzed in the dual SU(N) gauge theory on S{sup 3} with a time dependent coupling constant which varies slowly. When N{epsilon}<<1, we find that a quantum adiabatic approximation is applicable, and use it to argue that at late times the geometry becomes smooth AdS{sub 5}xS{sup 5} again. When N{epsilon}>>1, we formulate a classical adiabatic perturbation theory based on coherent states which arises in the large N limit. For large values of the 't Hooft coupling this reproduces the supergravity results. For small 't Hooft coupling the coherent state calculations become involved and we cannot reach a definite conclusion. We argue that the final state should have a dual description which is mostly smooth AdS{sub 5} space with the possible presence of a small black hole.

  5. SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein

    PubMed Central

    2013-01-01

    Objectives/background Ataxia with oculomotor apraxia defines a group of genetically distinct recessive ataxias including ataxia-telangectasia (A-T, ATM gene), ataxia with oculomotor apraxia type 1 (AOA1, APTX gene) and type 2 (AOA2, SETX gene). Although, a few unique clinical features differentiate each of these forms, the patients also share common clinical signs, such as the presence of cerebellar atrophy, sensorimotor axonal neuropathy, and elevated alpha-fetoprotein (AFP) serum level. Materials and methods We selected 22 Italian patients from 21 families, presenting progressive cerebellar ataxia, axonal neuropathy, and elevated serum AFP. We screened the coding regions of ATM, APTX and SETX genes for point mutations by direct sequencing or DHPLC, and searched genomic rearrangements in SETX by MLPA analysis. In selected cases, quantification of ATM and senataxin proteins was performed by Western blot. Clinical, neurophysiological, and neuroimaging data were collected. Results Thirteen patients (12 families) carried SETX mutations (AOA2, 57%), two were mutated in ATM (A-T), and three in APTX (AOA1). In three remaining patients, we could not find pathogenic mutations, and in one case we found, in homozygosis, the SETX p.K992R polymorphism (population frequency 1-2%). In AOA2 cases, we identified 14 novel and three reported SETX mutations. Signs at onset were gait ataxia and facial dyskinesia, and the age ranged between 11 and 18 years. None had obvious oculomotor apraxia at the latest examination (age 14–45 years). The patient carrying the p.K992R SETX polymorphism had a phenotype similar to that of the diagnosed AOA2 patients, while the other three undiagnosed subjects had a very late onset and a few distinguishing clinical features. Discussion and conclusions We describe a large series of 13 AOA2 Italian patients. The phenotype was consistent with previous descriptions of AOA2, except for a higher frequency of strabism, and for the absence of oculomotor

  6. Proprioceptive recalibration arises slowly compared to reach adaptation.

    PubMed

    Zbib, Basel; Henriques, Denise Y P; Cressman, Erin K

    2016-08-01

    When subjects reach in a novel visuomotor environment (e.g. while viewing a cursor representing their hand that is rotated from their hand's actual position), they typically adjust their movements (i.e. bring the cursor to the target), thus reducing reaching errors. Additionally, research has shown that reaching with altered visual feedback of the hand results in sensory changes, such that proprioceptive estimates of hand position are shifted in the direction of the visual feedback experienced (Cressman and Henriques in J Neurophysiol 102:3505-3518, 2009). This study looked to establish the time course of these sensory changes. Additionally, the time courses of implicit sensory and motor changes were compared. Subjects reached to a single visual target while seeing a cursor that was either aligned with their hand position (50 trials) or rotated 30° clockwise relative to their hand (150 trials). Reach errors and proprioceptive estimates of felt hand position were assessed following the aligned reach training trials and at seven different times during the rotated reach training trials by having subjects reach to the target without visual feedback, and provide estimates of their hand relative to a visual reference marker, respectively. Results revealed a shift in proprioceptive estimates throughout the rotated reach training trials; however, significant sensory changes were not observed until after 70 trials. In contrast, results showed a greater change in reaches after a limited number of reach training trials with the rotated cursor. These findings suggest that proprioceptive recalibration arises more slowly than reach adaptation. PMID:27014777

  7. The cerebellum ages slowly according to the epigenetic clock

    PubMed Central

    Horvath, Steve; Mah, Vei; Lu, Ake T.; Woo, Jennifer S.; Choi, Oi-Wa; Jasinska, Anna J.; Riancho, José A.; Tung, Spencer; Coles, Natalie S.; Braun, Jonathan; Vinters, Harry V.; Coles, L. Stephen

    2015-01-01

    Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages more slowly than other parts of the human body. We used both transcriptional data and genetic data to elucidate molecular mechanisms which may explain this finding. The two largest superfamilies of helicases (SF1 and SF2) are significantly over-represented (p=9.2×10−9) among gene transcripts that are over-expressed in the cerebellum compared to other brain regions from the same subject. Furthermore, SNPs that are associated with epigenetic age acceleration in the cerebellum tend to be located near genes from helicase superfamilies SF1 and SF2 (enrichment p=5.8×10−3). Our genetic and transcriptional studies of epigenetic age acceleration support the hypothesis that the slow aging rate of the cerebellum is due to processes that involve RNA helicases. PMID:26000617

  8. APT Observations of the Slowly Pulsating B Star HD 21071

    NASA Astrophysics Data System (ADS)

    Andrews, J. E.; Dukes, R. J.; Mills, L. R.

    2003-12-01

    We present an analysis of 4 seasons of APT data on the slowly pulsating B star HD21071. This star was found to be a variable with a period of 0.84 days by Waelkens. et. al. (1998, A&A, 330, 215) through an analysis of Hipparcos photometry. Earlier (Mills, L., et. al. 1999, BAAS, 31, 1482) reported on an analysis of the Hipparcos data combined with a partial season of APT data. This earlier paper confirmed the 0.84 day term and tentatively found a second term. Based on our additional data we confirm the second term of 0.870 days (1,149 c/d). We find that the amplitudes of these two terms have been nearly stable over the 4 seasons except for a slight increase in the amplitude of the 0.870 day term. There are suggestions of additional periodicities but to date we are unable to confirm these. Observations during the current season seem to show a greater scatter than previous seasons. At the time of this writing it is not possible to tell if this represents a real change in the star or possible instrumental effects. We will include observations from Fall 2003 in this paper. This research has made use of the SIMBAD database, operated at CDS, Strasbourg, France and has been funded by NSF Grants #AST95-28906, and #AST-0071260 to the College of Charleston.

  9. Slowly switching between environments facilitates reverse evolution in small populations.

    PubMed

    Tan, Longzhi; Gore, Jeff

    2012-10-01

    Natural populations must constantly adapt to ever-changing environmental conditions. A particularly interesting question is whether such adaptations can be reversed by returning the population to an ancestral environment. Such evolutionary reversals have been observed in both natural and laboratory populations. However, the factors that determine the reversibility of evolution are still under debate. The time scales of environmental change vary over a wide range, but little is known about how the rate of environmental change influences the reversibility of evolution. Here, we demonstrate computationally that slowly switching between environments increases the reversibility of evolution for small populations that are subject to only modest clonal interference. For small populations, slow switching reduces the mean number of mutations acquired in a new environment and also increases the probability of reverse evolution at each of these "genetic distances." As the population size increases, slow switching no longer reduces the genetic distance, thus decreasing the evolutionary reversibility. We confirm this effect using both a phenomenological model of clonal interference and also a Wright-Fisher stochastic simulation that incorporates genetic diversity. Our results suggest that the rate of environmental change is a key determinant of the reversibility of evolution, and provides testable hypotheses for experimental evolution. PMID:23025604

  10. THE MOST SLOWLY DECLINING TYPE Ia SUPERNOVA 2001ay

    SciTech Connect

    Krisciunas, Kevin; Gooding, Samuel D.; Li Weidong E-mail: sam.gooding86@gmail.com

    2011-09-15

    We present optical and near-infrared photometry, as well as ground-based optical spectra and Hubble Space Telescope ultraviolet spectra, of the Type Ia supernova (SN) 2001ay. At maximum light the Si II and Mg II lines indicated expansion velocities of 14,000 km s{sup -1}, while Si III and S II showed velocities of 9000 km s{sup -1}. There is also evidence for some unburned carbon at 12,000 km s{sup -1}. SN 2001ay exhibited a decline-rate parameter of {Delta}m{sub 15}(B) = 0.68 {+-} 0.05 mag; this and the B-band photometry at t {approx}> +25 day past maximum make it the most slowly declining Type Ia SN yet discovered. Three of the four super-Chandrasekhar-mass candidates have decline rates almost as slow as this. After correction for Galactic and host-galaxy extinction, SN 2001ay had M{sub B} = -19.19 and M{sub V} = -19.17 mag at maximum light; thus, it was not overluminous in optical bands. In near-infrared bands it was overluminous only at the 2{sigma} level at most. For a rise time of 18 days (explosion to bolometric maximum) the implied {sup 56}Ni yield was (0.58 {+-} 0.15)/{alpha} M{sub sun}, with {alpha} = L{sub max}/E{sub Ni} probably in the range 1.0-1.2. The {sup 56}Ni yield is comparable to that of many Type Ia SNe. The 'normal' {sup 56}Ni yield and the typical peak optical brightness suggest that the very broad optical light curve is explained by the trapping of {gamma} rays in the inner regions.

  11. Fetal programming, epigenetics, and adult onset disease.

    PubMed

    Lane, Robert H

    2014-12-01

    How early life events program adult disease is undergoing a transition from the broad field of maternal malnutrition to the current relevant issues of food deserts and prematurity. Although many adult diseases and morbidities associate with various early life events and programming, the morbidities of insulin resistance, cardiovascular disease, and obesity seem to be common end points of many early life events despite potential confounders. PMID:25459776

  12. Does a slowly varying component of solar irradiance exist?

    NASA Astrophysics Data System (ADS)

    Foukal, P.

    2003-04-01

    Fluctuations of total irradiance, S, caused by sunspots and faculae, are too small (˜0.1%) to force current climate models. Recent reconstructions of S incorporate an additional, slowly varying component, which follows the smoothed spot or group number, or the cycle period. But evidence for this larger (0.2--0.5%) variation, originally based on photometry of sun-like stars, is weakened by recent findings that true solar analog stars are difficult to find. Also, disappearance of the chromospheric network in the early 20th century, implied by these reconstructions, is not observed in archival solar images. I will show some new evidence for an additional component, suggested by the high correlation found between global temperature and the (small-amplitude) variation of S reconstructed using recently digitized facular areas between 1915--1999.The UV irradiance variation modeled from the same data exhibits much lower correlation with global warming, so it is less likely to account for a solar activity signature in 20th century climate. This indirect evidence suggests a mechanism that might amplify the small modulation of S caused specifically by the net effect of bright faculae and dark spots. We now recognize that amplification on multi-decadal time scales could only operate in near- photospheric layers, given the enormous thermal inertia of the deeper solar atmosphere. Also, increasingly tight constraints on such a mechanism are placed by solar photometry and radiometry, by spectro-photometric monitoring of the quiet photospheric effective temperature, and by absence of detectable solar diameter variations. The shrinking set of mechanisms that might satisfy these constraints deserves closer study, and I will discuss some interesting new observational diagnostics, such as bolometric imaging of the photosphere, planned to search for such processes. But at present, little direct evidence exists for a large-amplitude, multi-decadal variation of S (or of UV flux). A

  13. Number of women faculty in the geosciences increasing, but slowly

    NASA Astrophysics Data System (ADS)

    Wolfe, Cecily J.

    Why are there so few women faculty in the geosciences, while there are large numbers of women undergraduate and graduate students? According to National Science Foundation (NSF) estimates [e.g.,NSF, 1996] for 1995 in the Earth, atmospheric, and oceanic sciences, women made up 34% of the bachelor's degrees awarded, 35% of the graduate students enrolled, and 22% of the doctorates granted. Yet progress has been slower in achieving adequate representation of women geoscientists in academia, where women represent only 12% of the faculty. The barriers confronting the advancement of women scientists are complex and difficult to unravel. Proposed factors include cultural stereotypes, childhood socialization, lack of women mentors and role models, lack of critical mass, family responsibilities, dual-career-couple status, isolation from collegial networks, different research and publishing strategy, and less adequate access to institutional resources [c.f., Widnall, 1988; Zuckerman et al., 1991].

  14. Atypical gliosis in Müller cells of the slowly degenerating rds mutant mouse retina.

    PubMed

    Iandiev, Ianors; Biedermann, Bernd; Bringmann, Andreas; Reichel, Martin B; Reichenbach, Andreas; Pannicke, Thomas

    2006-03-01

    Retinal Müller glial cells are known to undergo reactive changes (gliosis) in various retinal diseases. In virtually all cases studied, an upregulation of glial fibrillary acidic protein (GFAP) and a hypertrophy can be observed. Physiological alterations, such as a strong downregulation of inwardly rectifying K+ (Kir) currents, were found after retinal detachment (man, rabbit) and after ischemia/reperfusion (rat) but not in more slowly progressing retinal degenerations (Borna Disease Virus-infected rats, RCS rats). This led us to hypothesize that Müller cells respond with 'typical' reactive gliosis only to rapid but not to slow retinal degeneration. To test this hypothesis, we studied Müller cells from rds mutant mice (PrphRd2), which show a retinal degeneration of early onset and slow progression, resulting in a complete loss of photoreceptors after 9-12 months. In Müller cells of rds mice, we found immunoreactivity for GFAP, a marker of gliosis in Müller cells, from postnatal day 21 on, accompanied by a moderately increased membrane capacitance (taken as an indicator of hypertrophy), whereas no change in the expression of the Kir4.1 protein occurred in adult rds mice. We failed to observe significant changes in the membrane resistance and the membrane potential of cells from rds mice from first week after birth until 1 year of age. Current densities were decreased in cells from 3- and 5-week old rds mice. Furthermore, as in control cells from wildtype animals, these cells displayed dominant Kir currents, voltage-dependent Na+ currents, and glutamate uptake currents. These data support the idea that in mice as well as previously shown in rats, slow retinal degeneration induces an atypical gliosis of Müller cells. PMID:16154566

  15. Stationary axisymmetric and slowly rotating spacetimes in Hořava-Lifshitz gravity.

    PubMed

    Wang, Anzhong

    2013-03-01

    Stationary, axisymmetric, and slowly rotating vacuum spacetimes in the Hořava-Lifshitz (HL) gravity are studied, and it is shown that, for any given spherical static vacuum solution of the HL theory (of any model, including the ones with an additional U(1) symmetry), there always exists a corresponding slowly rotating, stationary, and axisymmetric vacuum solution, which reduces to the former, when the rotation is switched off. The rotation is universal and only implicitly depends on the models of the HL theory and their coupling constants through the spherical seed solution. As a result, all asymptotically flat slowly rotating vacuum solutions are asymptotically identical to the slowly rotating Kerr solution. This is in contrast to the claim of Barausse and Sotiriou [Phys. Rev. Lett. 109, 181101 (2012)], in which slowly rotating black holes were reported (incorrectly) not to exist in the infrared limit of the nonprojectable HL theory. PMID:23496699

  16. Progressive myopathy with circulating autoantibody against giantin in the Golgi apparatus.

    PubMed

    Sahashi, K; Ibi, T; Ohno, K; Sahashi, K; Nakao, N; Kondo, H

    2004-05-25

    A woman aged 59 years with adult-onset progressive myopathy had anti-Golgi (giantin) autoantibody in the serum. Limb-muscle biopsy revealed chronic myopathy with paucity of cellular reactions and reduced immunostaining for alpha-dystroglycan. The similarity of the current patient with cases of hereditary alpha-dystroglycanopathies (Fukuyama-type congenital muscular dystrophy, Walker-Warburg syndrome, muscle-eye-brain disease, congenital muscular dystrophy type 1C, and limb-girdle muscular dystrophy type 2I) suggests that the Golgi apparatus is the target organelle in a subset of myopathies. PMID:15159505

  17. HD 18078: A very slowly rotating Ap star with an unusual magnetic field structure

    NASA Astrophysics Data System (ADS)

    Mathys, G.; Romanyuk, I. I.; Kudryavtsev, D. O.; Landstreet, J. D.; Pyper, D. M.; Adelman, S. J.

    2016-02-01

    Context. The existence of a significant population of Ap stars with very long rotation periods (up to several hundred years) has progressively emerged over the past two decades. However, only lower limits of the periods are known for most of them because their variations have not yet been observed over a sufficient timebase. Aims: We determine the rotation period of the slowly rotating Ap star HD 18078 and we derive constraints on the geometrical structure of its magnetic field. Methods: We combine measurements of the mean magnetic field modulus obtained from 1990 to 1997 with determinations of the mean longitudinal magnetic field spanning the 1999-2007 time interval to derive an unambiguous value of the rotation period. We show that this value is consistent with photometric variations recorded in the Strömgren uvby photometric system between 1995 and 2004. We fit the variations of the two above-mentioned field moments with a simple model to constrain the magnetic structure. Results: The rotation period of HD 18078 is (1358 ± 12) d. The geometrical structure of its magnetic field is consistent to first order with a colinear multipole model whose axis is offset from the centre of the star. Conclusions: HD 18078 is only the fifth Ap star with a rotation period longer than 1000 d for which the exact value of that period (as opposed to a lower limit) could be determined. The strong anharmonicity of the variations of its mean longitudinal magnetic field and the shift between their extrema and those of the mean magnetic field modulus are exceptional and indicative of a very unusual magnetic structure. Based in part on observations made at Observatoire de Haute Provence (CNRS), France; at Kitt Peak National Observatory, National Optical Astronomy Observatory (NOAO Prop. ID: KP2442; PI: T. Lanz), which is operated by the Association of Universities for Research in Astronomy (AURA) under cooperative agreement with the National Science Foundation; at the Canada

  18. Slowly changing potential problems in Quantum Mechanics: Adiabatic theorems, ergodic theorems, and scattering

    NASA Astrophysics Data System (ADS)

    Fishman, S.; Soffer, A.

    2016-07-01

    We employ the recently developed multi-time scale averaging method to study the large time behavior of slowly changing (in time) Hamiltonians. We treat some known cases in a new way, such as the Zener problem, and we give another proof of the adiabatic theorem in the gapless case. We prove a new uniform ergodic theorem for slowly changing unitary operators. This theorem is then used to derive the adiabatic theorem, do the scattering theory for such Hamiltonians, and prove some classical propagation estimates and asymptotic completeness.

  19. Fraction eutectic measurements in slowly cooled Pb - 15 wt percent Sn alloys

    NASA Technical Reports Server (NTRS)

    Studer, Anthony C.; Laxmanan, V.

    1988-01-01

    A space shuttle experiment employing the General Purpose Furnace in its isothermal mode of operation is currently manifested for flight circa 1989. The aim of this experiment was to investigate the role of gravity in a slowly, and isothermally, cooled sample of a binary Pb - 15 wt percent Sn alloy. Ground based work in support of the microgravity experiment is discussed. In particular, it is shown that fraction eutectic measurements using an image analyzer, can be used to satisfactorily describe macrosegregation occurring in these slowly cooled ingots.

  20. Hemispheric Specialization in Normally and Slowly Developing Children: A Tachistoscopic and Dichaptic Evaluation.

    ERIC Educational Resources Information Center

    Williams, H. G.; And Others

    1980-01-01

    Both right-and left-handed normally developing 6-year-olds showed considerable evidence of bilateralization of hemispheric functions for spatial and verbal information processing; the slowly developing children (ages 5-9) exhibited unusual patterns of hemispheric specialization usually opposite those typically expected in children or adults.…

  1. Study of velocities of dissipative Bragg solitons beyond the slowly-varying amplitude approximation

    SciTech Connect

    Rosanov, Nikolai N; Tran, X T

    2007-08-31

    The properties of dissipative solitons propagating in an active nonlinear fibre with a Bragg grating are studied without using the slowly-varying amplitude approximation. It is shown that dissipative solitons with close initial velocities acquire during their propagation certain values from a discrete set of velocities. (selected papers reported at the conference 'laser optics 2006')

  2. A study of bright southern slowly pulsating B stars. II. The intrinsic frequencies

    NASA Astrophysics Data System (ADS)

    De Cat, P.; Aerts, C.

    2002-10-01

    We present the results of detailed frequency analyses of a sample of thirteen confirmed slowly pulsating B stars. Our analysis is based on a combination of elaborate photometric and spectroscopic data-sets. The original sample consists of a mixture of five confirmed slowly pulsating B stars and twelve candidate slowly pulsating B stars discovered thanks to the photometric measurements of the HIPPARCOS satellite. HD 55522 and HD 131120 turn out to be chemically peculiar stars. HD 169978 and HD 69144 are two ellipsoidal variables for which no intrinsic variability is found. At least nine of the thirteen studied slowly pulsating B stars are multi-periodic. For HD 74195, HD 85953, HD 123515 and HD 215573, the observed frequency spacings suggest that we are dealing with frequency multiplets. For the apparent mono-periodic binary HD 24587, it is not clear if the observed variations are induced by stellar pulsation and/or by rotation modulation. We highlight the statistical character of the observed pulsational properties of our sample. Based on observations collected with the CAT Telescope of the European Southern Observatory and with the Swiss Photometric Telescope of the Geneva Observatory, both situated at La Silla in Chile Full Tables 2-4, 6-15 are only available in electronic form at the CDS via anounymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/393/965

  3. Slowly digestible starch diets alter proximal glucosidase activity and glucose absorption

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sucrase-isomaltase (Si) and maltase-glucoamylase (Mgam) are mucosal glucosidases required for digestion of starch to glucose. Ablation of maltase-Mgam reduces in vivo starch digestion. We tested whether slowly digestible starch diets induce changes in glucosidase activities. Rice starch was encaps...

  4. External Electromagnetic Fields of a Slowly Rotating Magnetized Star with Nonvanishing Gravitomagnetic Charge

    NASA Astrophysics Data System (ADS)

    Ahmedov, B. J.; Khugaev, A. V.; Rakhmatov, N. I.

    2008-09-01

    We write Maxwell equations in the external background spacetime of a slowly rotating magnetized NUT star and find analytical solutions after separating them into angular and radial parts. The star is considered isolated and in vacuum, with monopolar configuration model for the stellar magnetic field. The contribution to the external field from the NUT charge and frame-dragging effect are considered in detail.

  5. Characteristics of Quantum Radiation of Slowly Varying Nonstationary Kerr-Newman Black Holes

    NASA Astrophysics Data System (ADS)

    Hua, Jia-Chen; Huang, Yong-Chang

    Quantum radiative characteristics of slowly varying nonstationary Kerr-Newman black holes are investigated by using the method of generalized tortoise coordinate transformation. It is shown that the temperature and the shape of the event horizon of this kind of black holes depend on the time and the angle. Further, we reveal a previously ignored relationship between thermal radiation and nonthermal radiation, which is that the chemical potential in the thermal radiation spectrum is equal to the highest energy of the negative energy state of particles in nonthermal radiation for slowly varying nonstationary Kerr-Newman black holes. Also, we show that the deduced general results can be degenerated to the known conclusion of stationary Kerr-Newman black holes.

  6. Slowly moving test charge in two-electron component non-Maxwellian plasma

    SciTech Connect

    Ali, S.; Eliasson, B.

    2015-08-15

    Potential distributions around a slowly moving test charge are calculated by taking into account the electron-acoustic waves in an unmagnetized plasma. Considering a neutralizing background of static positive ions, the supra-thermal hot and cold electrons are described by the Vlasov equations to account for the Kappa (power-law in velocity space) and Maxwell equilibrium distributions. Fourier analysis further leads to the derivation of electrostatic potential showing the impact of supra-thermal hot electrons. The test charge moves slowly in comparison with the hot and cold electron thermal speeds and is therefore shielded by the electrons. This gives rise to a short-range Debye-Hückel potential decaying exponentially with distance and to a far field potential decaying as inverse third power of the distance from the test charge. The results are relevant for both laboratory and space plasmas, where supra-thermal hot electrons with power-law distributions have been observed.

  7. Electron paramagnetic resonance studies of slowly tumbling vanadyl spin probes in nematic liquid crystals

    NASA Technical Reports Server (NTRS)

    Bruno, G. V.; Harrington, J. K.; Eastman, M. P.

    1978-01-01

    An analysis of EPR line shapes by the method of Polnaszek, Bruno, and Freed is made for slowly tumbling vanadyl spin probes in viscous nematic liquid crystals. The use of typical vanadyl complexes as spin probes for nematic liquid crystals is shown to simplify the theoretical analysis and the subsequent interpretation. Rotational correlation times tau and orientational ordering parameters S sub Z where slow tumbling effects are expected to be observed in vanadyl EPR spectra are indicated in a plot. Analysis of the inertial effects on the probe reorientation, which are induced by slowly fluctuating torque components of the local solvent structure, yield quantitative values for tau and S sub Z. The weakly ordered probe VOAA is in the slow tumbling region and displays these inertial effects throughout the nematic range of BEPC and Phase V. VOAA exhibits different reorientation behavior near the isotropic-nematic transition temperature than that displayed far below this transition temperature.

  8. Equatorial superrotation in a slowly rotating GCM - Implications for Titan and Venus

    NASA Astrophysics Data System (ADS)

    del Genio, A. D.; Zhou, W.; Eichler, T. P.

    1993-01-01

    The GISS GCM is used here to examine the hypothesis that equatorial superrotation on slowly rotating planets is sensitive to the nature of the vertical radiative heating profile and can exist in the absence of diurnally varying forcing. The general circulation, diabatic heating, and thermal structure produced in the experiments are described and the heat and angular momentum budgets and energy cycles are analyzed to understand the factors conducive to equatorial superrotation. The implications of the results for future planetary missions are addressed.

  9. External electromagnetic fields of a slowly rotating magnetized star with gravitomagnetic charge

    NASA Astrophysics Data System (ADS)

    Ahmedov, B. J.; Khugaev, A. V.; Abdujabbarov, A. A.

    2012-02-01

    We study Maxwell equations in the external background spacetime of a slowly rotating magnetized NUT star and find analytical solutions for the exterior electric fields after separating the equations for electric field into angular and radial parts in the lowest order in angular momentum and NUT charge approximation. The star is considered isolated and in vacuum, with dipolar magnetic field aligned with the axis of rotation. The contribution to the external electric field of star from the NUT charge is considered in detail.

  10. A slowly rotating coil system for AC field measurements of Fermilab booster correctors

    SciTech Connect

    Velev, G.; DiMarco, J.; Harding, David J.; Kashikhin, V.; Lamm, Michael J.; Schlabach, P.; Tartaglia, Michael Albert; Tompkins, John C.; /Fermilab

    2007-06-01

    A method for measurement of rapidly changing magnetic fields has been developed and applied to the testing of new room temperature corrector packages designed for the Fermilab Booster Synchrotron. The method is based on fast digitization of a slowly rotating tangential coil probe, with analysis combining the measured coil voltages across a set of successive magnet current cycles. This paper presents results on the field quality measured for the normal and skew dipole, quadrupole, and sextupole elements in several of these corrector packages.

  11. Gaussian beams for surface waves in laterally slowly-varying media

    NASA Technical Reports Server (NTRS)

    Yomogida, K.

    1985-01-01

    Asymptotic ray theory is applied to surface waves in a medium where the lateral variations of structure are very smooth. The elastodynamic equations of motion in ray-centered coordinates are derived, and a laterally slowly-varying approximation for elastodynamic equations is obtained. Parabolic equations for Love and Rayleigh waves are studied and solved, and the properties of Gaussian beams of seismic surface waves are examined.

  12. Slowly rotating neutron and strange stars in R{sup 2} gravity

    SciTech Connect

    Staykov, Kalin V.; Yazadjiev, Stoytcho S.; Doneva, Daniela D.; Kokkotas, Kostas D. E-mail: daniela.doneva@uni-tuebingen.de E-mail: kostas.kokkotas@uni-tuebingen.de

    2014-10-01

    In the present paper we investigate self-consistently slowly rotating neutron and strange stars in R-squared gravity with Lagrangian f(R) = R + aR{sup 2}, where a is a parameter. For this purpose we first derive the equations describing the structure of the slowly rotating compact stars in f(R)-gravity and then simultaneously solve numerically the exterior and the interior problem. The structure of the slowly rotating neutron stars is studied for two different hadronic equations of state and a strange matter equation of state. The moment of inertia and its dependence on the stellar mass and the R-squared gravity parameter a is also examined in details. The numerical results show that the neutron star moment of inertia can be up to 30% larger compared to the corresponding general relativistic models. This is much higher than the change in the maximum mass induced by R-squared gravity and is beyond the EOS uncertainty. In this way the future observations of the moment of inertia of compact stars could allow us to distinguish between general relativity and f(R) gravity, and more generally to test the strong field regime of gravity.

  13. Mycobacterium shottsii sp. nov., a slowly growing species isolated from Chesapeake Bay striped bass (Morone saxatilis)

    USGS Publications Warehouse

    Rhodes, M.W.; Kator, H.; Kotob, S.; van Berkum, P.; Kaattari, I.; Vogelbein, W.; Quinn, F.; Floyd, M.M.; Butler, W.R.; Ottinger, C.A.

    2003-01-01

    Slowly growing, non-pigmented mycobacteria were isolated from striped bass (Morone saxatilis) during an epizootic of mycobacteriosis in the Chesapeake Bay. Growth characteristics, acid-fastness and results of 16S rRNA gene sequencing were consistent with those of the genus Mycobacterium. A unique profile of biochemical reactions was observed among the 21 isolates. A single cluster of eight peaks identified by analysis of mycolic acids (HPLC) resembled those of reference patterns but differed in peak elution times from profiles of reference species of the Mycobacterium tuberculosis complex. One isolate (M175T) was placed within the slowly growing mycobacteria by analysis of aligned 16S rRNA gene sequences and was proximate in phylogeny to Mycobacterium ulcerans and Mycobacterium marinum. However, distinct nucleotide differences were detected in the 16S rRNA gene sequence among M175T, M. ulcerans and M. marinum (99.2% similarity). Isolate M175T could be differentiated from other slowly growing, non-pigmented mycobacteria by its inability to grow at 37??C, production of niacin and urease, absence of nitrate reductase and resistance to isoniazid (1 ??g ml-1), thiacetazone and thiophene-2-carboxylic hydrazide. Based upon these genetic and phenotypic differences, isolate M175T (= ATCC 700981T = NCTC 13215T) is proposed as the type strain of a novel species, Mycobacterium shottsii sp. nov.

  14. Prostate cancer stem-like cells proliferate slowly and resist etoposide-induced cytotoxicity via enhancing DNA damage response

    SciTech Connect

    Yan, Judy; Tang, Damu

    2014-10-15

    Despite the development of chemoresistance as a major concern in prostate cancer therapy, the underlying mechanisms remain elusive. In this report, we demonstrate that DU145-derived prostate cancer stem cells (PCSCs) progress slowly with more cells accumulating in the G1 phase in comparison to DU145 non-PCSCs. Consistent with the important role of the AKT pathway in promoting G1 progression, DU145 PCSCs were less sensitive to growth factor-induced activation of AKT in comparison to non-PCSCs. In response to etoposide (one of the most commonly used chemotherapeutic drugs), DU145 PCSCs survived significantly better than non-PCSCs. In addition to etoposide, PCSCs demonstrated increased resistance to docetaxel, a taxane drug that is commonly used to treat castration-resistant prostate cancer. Etoposide produced elevated levels of γH2AX and triggered a robust G2/M arrest along with a coordinated reduction of the G1 population in PCSCs compared to non-PCSCs, suggesting that elevated γH2AX plays a role in the resistance of PCSCs to etoposide-induced cytotoxicity. We have generated xenograft tumors from DU145 PCSCs and non-PCSCs. Consistent with the knowledge that PCSCs produce xenograft tumors with more advanced features, we were able to demonstrate that PCSC-derived xenograft tumors displayed higher levels of γH2AX and p-CHK1 compared to non-PCSC-produced xenograft tumors. Collectively, our research suggests that the elevation of DNA damage response contributes to PCSC-associated resistance to genotoxic reagents. - Highlights: • Increased survival in DU145 PCSCs following etoposide-induced cytotoxicity. • PCSCs exhibit increased sensitivity to etoposide-induced DDR. • Resistance to cytotoxicity may be due to slower proliferation in PCSCs. • Reduced kinetics to growth factor induced activation of AKT in PCSCs.

  15. Chemical transfers along slowly eroding catenas developed on granitic cratons in southern Africa

    USGS Publications Warehouse

    Khomo, Lesego; Bern, Carleton R.; Hartshorn, Anthony S.; Rogers, Kevin H.; Chadwick, Oliver A.

    2013-01-01

    A catena is a series of distinct but co-evolving soils arrayed along a slope. On low-slope, slowly eroding catenas the redistribution of mass occurs predominantly as plasma, the dissolved and suspended constituents in soil water. We applied mass balance methods to track how redistribution via plasma contributed to physical and geochemical differentiation of nine slowly eroding (~ 5 mm ky− 1) granitic catenas. The catenas were arrayed in a 3 × 3 climate by relief matrix and located in Kruger National Park, South Africa. Most of the catenas contained at least one illuviated soil profile that had undergone more volumetric expansion and less mass loss, and these soils were located in the lower halves of the slopes. By comparison, the majority of slope positions were eluviated. Soils from the wetter climates (550 and 730 mm precipitation yr− 1) generally had undergone greater collapse and lost more mass, while soils in the drier climate (470 mm yr− 1) had undergone expansion and lost less mass. Effects of differences in catena relief were less clear. Within each climate zone, soil horizon mass loss and strain were correlated, as were losses of most major elements, illustrating the predominant influence of primary mineral weathering. Nevertheless, mass loss and volumetric collapse did not become extreme because of the skeleton of resistant primary mineral grains inherited from the granite. Colloidal clay redistribution, as traced by the ratio of Ti to Zr in soil, suggested clay losses via suspension from catena eluvial zones. Thus illuviation of colloidal clays into downslope soils may be crucial to catena development by restricting subsurface flow there. Our analysis provides quantitative support for the conceptual understanding of catenas in cratonic landscapes and provides an endmember reference point in understanding the development of slowly eroding soil landscapes.

  16. Envelope function method for electrons in slowly-varying inhomogeneously deformed crystals.

    PubMed

    Li, Wenbin; Qian, Xiaofeng; Li, Ju

    2014-11-12

    We develop a new envelope-function formalism to describe electrons in slowly-varying inhomogeneously strained semiconductor crystals. A coordinate transformation is used to map a deformed crystal back to a geometrically undeformed structure with deformed crystal potential. The single-particle Schrödinger equation is solved in the undeformed coordinates using envelope function expansion, wherein electronic wavefunctions are written in terms of strain-parametrized Bloch functions modulated by slowly varying envelope functions. Adopting a local approximation of the electronic structure, the unknown crystal potential in the Schrödinger equation can be replaced by the strain-parametrized Bloch functions and the associated strain-parametrized energy eigenvalues, which can be constructed from unit-cell level ab initio or semi-empirical calculations of homogeneously deformed crystals at a chosen crystal momentum. The Schrödinger equation is then transformed into a coupled differential equation for the envelope functions and solved as a generalized matrix eigenvector problem. As the envelope functions are slowly varying, a coarse spatial or Fourier grid can be used to represent the envelope functions, enabling the method to treat relatively large systems. We demonstrate the effectiveness of this method using a one-dimensional model, where we show that the method can achieve high accuracy in the calculation of energy eigenstates with relatively low cost compared to direct diagonalization of the Hamiltonian. We further derive envelope function equations that allow the method to be used empirically, in which case certain parameters in the envelope function equations will be fitted to experimental data. PMID:25336522

  17. Slowly digestible state of starch: mechanism of slow digestion property of gelatinized maize starch.

    PubMed

    Zhang, Genyi; Sofyan, Maghaydah; Hamaker, Bruce R

    2008-06-25

    The mechanism underlying the previously reported parabolic relationship between amylopectin fine structure, represented by the weight ratio of linear short chains [degree of polymerization (DP < 13) to long chains (DP >/= 13], and slowly digestible starch (SDS) content was investigated from the viewpoint of starch retrogradation and substrate susceptibility to enzyme hydrolysis. A maize mutant sample, termed "highest long-chain starch" (HLCS) representing group I samples with a higher proportion of long chains, showed a bell-shaped SDS pattern with retrogradation time, whereas insignificant changes in SDS were found for the sample termed "highest short-chain starch" (HSCS) representing group II samples with a higher proportion of short chains. This corresponded to results from X-ray powder diffraction and differential scanning calorimetry that showed a rapid increase of crystallinity and enthalpy for HLCS during retrogradation, but negligible changes for sample HSCS. Therefore, retrogradation was associated with SDS content for group I samples, but not for group II samples. Analysis of amylopectin fine structure, SDS content, retrogradation enthalpy, SDS material debranching profile, and hydrolysis pattern demonstrated, for group I samples, that linear branched chains of DP 9-30 of amylopectin may act as anchor points to slow the digestion of branced-chain fractions of DP > 30, which constitute the major slowly digestible portion, whereas for group II samples, it is the inherent molecular structure of amylopectin with a higher amount of branches and shorter chains that is not favorable for rapid enzyme digestion. The concept of a slowly digestible starch state (SDS state) that could be a chemical or physical entity is proposed to better describe the mechanistic underpinning of the slow digestion property of starches. PMID:18512933

  18. Fast Solar Wind from Slowly Expanding Magnetic Flux Tubes (P54)

    NASA Astrophysics Data System (ADS)

    Srivastava, A. K.; Dwivedi, B. N.

    2006-11-01

    aks.astro.itbhu@gmail.com We present an empirical model of the fast solar wind, emanating from radially oriented slowly expanding magnetic flux tubes. We consider a single-fluid, steady state model in which the flow is driven by thermal and non-thermal pressure gradients. We apply a non-Alfvénic energy correction at the coronal base and find that specific relations correlate solar wind speed and non-thermal energy flux with the aerial expansion factor. The results are compared with the previously reported ones.

  19. Extended solution space for Chern-Simons gravity: The slowly rotating Kerr black hole

    SciTech Connect

    Cambiaso, Mauro; Urrutia, Luis F.

    2010-11-15

    In the Einstein-Cartan formulation, an iterative procedure to find solutions in nondynamical Chern-Simons gravity in vacuum is proposed. The iterations, in powers of a small parameter {beta} which codifies the Chern-Simons coupling, start from an arbitrary torsionless solution of Einstein equations. With Schwarzschild as the zeroth-order choice, we derive a second-order differential equation for the O({beta}) corrections to the metric, for an arbitrary zeroth-order embedding parameter. In particular, the slowly rotating Kerr metric is an O({beta}) solution in either the canonical or the axial embeddings.

  20. Formation of Slowly Rotating Elliptical Galaxies in Major Mergers. A Resolution Study

    NASA Astrophysics Data System (ADS)

    Bois, M.; Bournaud, F.; Emsellem, E.; Alatalo, K.; Blitz, L.; Bureau, M.; Cappellari, M.; Davies, R. L.; Davis, T. A.; de Zeeuw, P. T.; Falcón-Barroso, J.; Khochfar, S.; Krajnović, D.; Kuntschner, H.; Lablanche, P.-Y.; McDermid, R. M.; Morganti, R.; Naab, T.; Sarzi, M.; Scott, N.; Serra, P.; van den Bosch, R. C. E.; van de Ven, G.; Weijmans, A.; Young, L. M.

    2010-06-01

    We study resolution effects in numerical simulations of gas-rich (20% of the total baryonic mass) major mergers, and show that the formation of slowly-rotating elliptical galaxies requires a resolution that is beyond the present-day standards to be properly modelled. Our findings show that a high-enough resolution is required to accurately model the global properties of merger remnants and the evolution of their angular momentum. The role of wet mergers of spiral galaxies in the formation of slow-rotating ellipticals may therefore have been underestimated.

  1. A search for slowly varying radio continuum emission from UV Ceti stars

    NASA Technical Reports Server (NTRS)

    Spangler, S. R.; Shawhan, S. D.

    1976-01-01

    The paper presents results of a search conducted at the Arecibo Observatory for variable 430-MHz emission from the active flare stars EQ Peg, YZ CMi, and AD Leo. No statistically significant evidence for slowly varying emission is found to a level of 0.05 Jy for AD Leo, 0.018-0.021 Jy for YZ CMi, and 0.009-0.018 Jy for EQ Peg. Upper limits of about 10 trillion K are determined for the brightness temperature of active radio regions on these stars at the time of the observations.

  2. [A Case of Slowly Growing Primary Malignant Lymphoma of the Epididymis].

    PubMed

    Urabe, Fumihiko; Tashiro, Kojiro; Kimura, Shoji; Kimura, Takahiro; Miki, Kenta; Takahashi, Hiroyuki; Egawa, Shin

    2015-12-01

    A 30-year-old man who had a painless mass in the right scrotum since 5 years ago underwent biopsy followed by right high orchiectomy. The tumor originating from the epididymis was histologically diagnosed as a malignant lymphoma (a diffuse large B-cell lymphoma). The tumor grew very slowly even though the MIB-1 index was more than 90%. The patient underwent six courses of R-CHOP chemotherapy, intrathecal administration of methotrexate, and radiation therapy to the contralateral testis. Currently, 10 months after surgery, the patient has shown no clinical evidence of recurrence. PMID:26790768

  3. Reservoir computing with a slowly modulated mask signal for preprocessing using a mutually coupled optoelectronic system

    NASA Astrophysics Data System (ADS)

    Tezuka, Miwa; Kanno, Kazutaka; Bunsen, Masatoshi

    2016-08-01

    Reservoir computing is a machine-learning paradigm based on information processing in the human brain. We numerically demonstrate reservoir computing with a slowly modulated mask signal for preprocessing by using a mutually coupled optoelectronic system. The performance of our system is quantitatively evaluated by a chaotic time series prediction task. Our system can produce comparable performance with reservoir computing with a single feedback system and a fast modulated mask signal. We showed that it is possible to slow down the modulation speed of the mask signal by using the mutually coupled system in reservoir computing.

  4. Slowly Replicating Lytic Viruses: Pseudolysogenic Persistence and Within-Host Competition

    NASA Astrophysics Data System (ADS)

    Zhang, Jingshan; Shakhnovich, Eugene I.

    2009-05-01

    We study the population dynamics of lytic viruses which replicate slowly in dividing host cells within an organism or cell culture, and find a range of viral replication rates that allows viruses to persist, avoiding extinction of host cells or dilution of viruses at too rapid or too slow viral replication. For the within-host competition between viral strains with different replication rates, a strain with a “stable” replication rate in the persistence range could outcompete another strain. However, when strains with higher and lower than the stable value replication rates are both present, competition between strains does not result in the dominance of one strain, but in their coexistence.

  5. Structural analysis of biofilm formation by rapidly and slowly growing nontuberculous mycobacteria.

    PubMed

    Williams, Margaret M; Yakrus, Mitchell A; Arduino, Matthew J; Cooksey, Robert C; Crane, Christina B; Banerjee, Shailen N; Hilborn, Elizabeth D; Donlan, Rodney M

    2009-04-01

    Mycobacterium avium complex (MAC) and rapidly growing mycobacteria (RGM) such as M. abscessus, M. mucogenicum, M. chelonae, and M. fortuitum, implicated in health care-associated infections, are often isolated from potable water supplies as part of the microbial flora. To understand factors that influence growth in their environmental source, clinical RGM and slowly growing MAC isolates were grown as biofilm in a laboratory batch system. High and low nutrient levels were compared, as well as stainless steel and polycarbonate surfaces. Biofilm growth was measured after 72 h of incubation by enumeration of bacteria from disrupted biofilms and by direct quantitative image analysis of biofilm microcolony structure. RGM biofilm development was influenced more by nutrient level than by substrate material, though both affected biofilm growth for most of the isolates tested. Microcolony structure revealed that RGM develop several different biofilm structures under high-nutrient growth conditions, including pillars of various shapes (M. abscessus and M. fortuitum) and extensive cording (M. abscessus and M. chelonae). Although it is a slowly growing species in the laboratory, a clinical isolate of M. avium developed more culturable biofilm in potable water in 72 h than any of the 10 RGM examined. This indicates that M. avium is better adapted for growth in potable water systems than in laboratory incubation conditions and suggests some advantage that MAC has over RGM in low-nutrient environments. PMID:19201956

  6. HERSCHEL AND SPITZER OBSERVATIONS OF SLOWLY ROTATING, NEARBY ISOLATED NEUTRON STARS

    SciTech Connect

    Posselt, B.; Pavlov, G. G.; Popov, S.; Wachter, S.

    2014-11-01

    Supernova fallback disks around neutron stars have been suspected to influence the evolution of the diverse neutron star populations. Slowly rotating neutron stars are the most promising places to find such disks. Searching for the cold and warm debris of old fallback disks, we carried out Herschel PACS (70 μm, 160 mu m) and Spitzer IRAC (3.6 μm, 4.5 μm) observations of eight slowly rotating (P ≈ 3-11 s) nearby (<1 kpc) isolated neutron stars. Herschel detected 160 μm emission (>5σ) at locations consistent with the positions of the neutron stars RX J0806.4-4123 and RX J2143.0+0654. No other significant infrared emission was detected from the eight neutron stars. We estimate probabilities of 63%, 33%, and 3% that, respectively, none, one, or both Herschel PACS 160 μm detections are unrelated excess sources due to background source confusion or an interstellar cirrus. If the 160 μm emission is indeed related to cold (10-22 K) dust around the neutron stars, this dust is absorbing and re-emitting ∼10% to ∼20% of the neutron stars' X-rays. Such high efficiencies would be at least three orders of magnitude larger than the efficiencies of debris disks around nondegenerate stars. While thin dusty disks around the neutron stars can be excluded as counterparts of the 160 μm emission, dusty asteroid belts constitute a viable option.

  7. Position-dependent chemotactic response of slowly migrating cells in sigmoidal concentration profiles

    NASA Astrophysics Data System (ADS)

    Renner, A.; Jaeger, M. S.; Lankenau, A.; Duschl, C.

    2013-09-01

    Characterizing the chemotactic motility of slowly migrating cells as a function of time is still challenging. In this paper, we use a microfluidic device for investigating the chemotactic activity of HFF-1 fibroblasts in a sigmoidal concentration profile of epidermal growth factor (EGF). Sigmoidal concentration profiles are very common in biological systems but, in contrast to linear gradients, are much less studied in microfluidic systems. We monitored cell migration for up to 10 hours and found that chemotaxis is strongest where the absolute EGF concentration is below 25 pM ( K D of EGF is 1 nM). Calculating the fraction of receptor occupancy ( FRO) at the front and rear of the cells showed that the chemotactic activity of HFF-1 cells scaled with the difference in FRO between both ends of the cell normalized by the average FRO av of the cell. Interestingly, the mean chemotactic index of the cells was found to be a function of the gradient at the starting position and did not change when cells were entering into other regions of the highly non-linear concentration profile. Our studies demonstrate the usefulness of stable sigmoidal concentration profiles produced in microfluidic channels for a detailed analysis of the chemotactic response of slowly migrating cells.

  8. Herschel and Spitzer Observations of Slowly Rotating, Nearby Isolated Neutron Stars

    NASA Astrophysics Data System (ADS)

    Posselt, B.; Pavlov, G. G.; Popov, S.; Wachter, S.

    2014-11-01

    Supernova fallback disks around neutron stars have been suspected to influence the evolution of the diverse neutron star populations. Slowly rotating neutron stars are the most promising places to find such disks. Searching for the cold and warm debris of old fallback disks, we carried out Herschel PACS (70 μm, 160 μm) and Spitzer IRAC (3.6 μm, 4.5 μm) observations of eight slowly rotating (P ≈ 3-11 s) nearby (<1 kpc) isolated neutron stars. Herschel detected 160 μm emission (>5σ) at locations consistent with the positions of the neutron stars RX J0806.4-4123 and RX J2143.0+0654. No other significant infrared emission was detected from the eight neutron stars. We estimate probabilities of 63%, 33%, and 3% that, respectively, none, one, or both Herschel PACS 160 μm detections are unrelated excess sources due to background source confusion or an interstellar cirrus. If the 160 μm emission is indeed related to cold (10-22 K) dust around the neutron stars, this dust is absorbing and re-emitting ~10% to ~20% of the neutron stars' X-rays. Such high efficiencies would be at least three orders of magnitude larger than the efficiencies of debris disks around nondegenerate stars. While thin dusty disks around the neutron stars can be excluded as counterparts of the 160 μm emission, dusty asteroid belts constitute a viable option.

  9. Characteristics of sarcoplasmic reticulum from slowly glycolysing and from rapidly glycolysing pig skeletal muscle post mortem

    PubMed Central

    McIntosh, David B.; Berman, Mervyn C.; Kench, James E.

    1977-01-01

    The composition and function of fragmented sarcoplasmic reticulum from pig skeletal muscle was examined in the period immediately post mortem. Muscle was defined as being either slowly glycolysing or rapidly glycolysing on the basis of colour, pH and concentrations of glycogen and lactate. The microsomal fraction was separated on a discontinuous gradient of 35, 40 and 45% (w/v) sucrose into heavy and intermediate fractions which sedimented to the interfaces, and a light fraction which remained on the surface of the 35%-sucrose layer. The sarcoplasmic reticulum from rapidly glycolysing muscle had a lower buoyant density than had that from slowly glycolysing muscle. This was reflected in the consistent lack of material in the heavy fraction and a greater proportion in the light fraction. The latter material had significantly lower ratios (w/w) of protein to phospholipid (2.3:1 versus 3.8:1) and of protein to cholesterol (10.4:1 versus 15.6:1). There were no gross differences in phospholipid content or in fatty acid composition of individual phospholipid classes in the membranes from the two types of muscle. Analysis of membrane proteins by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis showed that ATPase (adenosine triphosphatase) was a major component of each fraction and that its contribution to the total protein content of the membrane was greater in rapidly glycolysing muscle, suggesting a loss of non-ATPase proteins. The two fractions of sarcoplasmic reticulum prepared from rapidly glycolysing muscle had approximately one-third the normal activities of Ca2+ binding and Ca2+ uptake in the presence of ATP and one-half the passive Ca2+-binding capacity in the absence of ATP of the fractions from slowly glycolysing muscle. However, the (Ca2++Mg2+)-stimulated ATPase activities were similar. Efflux from actively loaded vesicles, after the addition of EDTA, consisted of a rapid and a slow phase. Vesicles from rapidly glycolysing muscle lost 60% of

  10. Piperidinyl thiazole isoxazolines: A new series of highly potent, slowly reversible FAAH inhibitors with analgesic properties.

    PubMed

    Pember, Stephen O; Mejia, Galo L; Price, Theodore J; Pasteris, Robert J

    2016-06-15

    Fatty acid amide hydrolase (FAAH) is a membrane anchored serine hydrolase that has a principle role in the metabolism of the endogenous cannabinoid anandamide. Docking studies using representative FAAH crystal structures revealed that compounds containing a novel piperidinyl thiazole isoxazoline core fit within the ligand binding domains. New potential FAAH inhibitors were designed and synthesized incorporating urea, carbamate, alkyldione and thiourea reactive centers as potential pharmacophores. A small library of candidate compounds (75) was then screened against human FAAH leading to the identification of new carbamate and urea based inhibitors (Ki=pM and nM, respectively). Representative carbamate and urea based chemotypes displayed slow, time dependent inhibition kinetics leading to enzyme inactivation which was slowly reversible. However, evidence indicated that features of the mechanism of inactivation differ between the two pharmacophore types. Selected compounds were also evaluated for analgesic activity in the mouse-tail flick test. PMID:27130358

  11. Monodisperse, polymeric microspheres produced by irradiation of slowly thawing frozen drops

    NASA Technical Reports Server (NTRS)

    Rhim, Won-Kyu (Inventor); Hyson, Michael T. (Inventor); Chung, Sang-Kun (Inventor); Colvin, Michael S. (Inventor); Chang, Manchium (Inventor)

    1991-01-01

    Monodisperse, polymeric microspheres are formed by injecting uniformly shaped droplets of radiation polymerizable monomers, preferably a biocompatible monomer, having covalent binding sites such as hydroxyethylmethacrylate, into a zone, impressing a like charge on the droplet so that they mutually repel each other, spheroidizing the droplets within the zone and collecting the droplets in a pool of cryogenic liquid. As the droplets enter the liquid, they freeze into solid, glassy microspheres, which vaporizes a portion of the cryogenic liquid to form a layer. The like-charged microspheres, suspended within the layer, move to the edge of the vessel holding the pool, are discharged, fall and are collected. The collected microspheres are irradiated while frozen in the cryogenic liquid to form latent free radicals. The frozen microspheres are then slowly thawed to activate the free radicals which polymerize the monomer to form evenly-sized, evenly-shaped, monodisperse polymeric microspheres.

  12. The slowly varying corona from DEMs with the EVE data set

    NASA Astrophysics Data System (ADS)

    Schonfeld, Samuel J.; White, Stephen M.; Hock, Rachel A.; McAteer, James

    2016-05-01

    We present a differential emission measure (DEM) analysis of the slowly varying corona during the first half of solar cycle 24. Using the Extreme ultraviolet Variability Experiment (EVE) and the CHIANTI atomic line database we identify strong isolated iron emission lines present in the non-flaring spectrum with peak emissions covering the coronal temperature range of 5.7 < log(T) < 6.5. These lines are used to generate daily DEMs from EVE spectra to observe the long term variability of global coronal thermal properties. We discuss the choice of emission lines and the implications of this data set for the relationship between EUV and the F10.7 radio flux.

  13. Power law statistics of force and acoustic emission from a slowly penetrated granular bed

    NASA Astrophysics Data System (ADS)

    Matsuyama, K.; Katsuragi, H.

    2014-01-01

    Penetration-resistant force and acoustic emission (AE) from a plunged granular bed are experimentally investigated through their power law distribution forms. An AE sensor is buried in a glass bead bed. Then, the bed is slowly penetrated by a solid sphere. During the penetration, the resistant force exerted on the sphere and the AE signal are measured. The resistant force shows power law relation to the penetration depth. The power law exponent is independent of the penetration speed, while it seems to depend on the container's size. For the AE signal, we find that the size distribution of AE events obeys power laws. The power law exponent depends on grain size. Using the energy scaling, the experimentally observed power law exponents are discussed and compared to the Gutenberg-Richter (GR) law.

  14. On-Line Modal State Monitoring of Slowly Time-Varying Structures

    NASA Technical Reports Server (NTRS)

    Johnson, Erik A.; Bergman, Lawrence A.; Voulgaris, Petros G.

    1997-01-01

    Monitoring the dynamic response of structures is often performed for a variety of reasons. These reasons include condition-based maintenance, health monitoring, performance improvements, and control. In many cases the data analysis that is performed is part of a repetitive decision-making process, and in these cases the development of effective on-line monitoring schemes help to speed the decision-making process and reduce the risk of erroneous decisions. This report investigates the use of spatial modal filters for tracking the dynamics of slowly time-varying linear structures. The report includes an overview of modal filter theory followed by an overview of several structural system identification methods. Included in this discussion and comparison are H-infinity, eigensystem realization, and several time-domain least squares approaches. Finally, a two-stage adaptive on-line monitoring scheme is developed and evaluated.

  15. Entropy of Non-stationary and Slowly Changing Reissner-Nordström Black Hole

    NASA Astrophysics Data System (ADS)

    Yan, Han

    2014-01-01

    Simplifying Dirac equation near the horizon, Hawking temperature is obtained by applying a new tortoise coordinate transformation. Using the improved thin film brick-wall model and WKB approximation, the entropy of Dirac field in the non-stationary and slowly changing Reissner-Nordström black hole is calculated. The result shows that the entropy of the black hole is still proportional to the horizon area, and black hole entropy is just identical to the entropy of the quantum state at the horizon. In addition, the new tortoise coordinate transformation can make the cut-off parameter introduced in solving the entropy of non-stationary black hole simplified to the same as that in the static and stationary cases.

  16. Aerodynamics of the knuckleball pitch: Experimental measurements on slowly rotating baseballs

    NASA Astrophysics Data System (ADS)

    Borg, John P.; Morrissey, Michael P.

    2014-10-01

    In this work, we characterize the lift and lateral forces on a two-seam versus four-seam knuckleball and measure the viscous shear stress. We believe these measurements to be the first reported for slowly rotating baseballs. Our findings indicate the seam acts to either delay or advance separation depending upon the ball angle; these results are supported with flow visualization. The combined effect produces significant lift and lateral forces that can rapidly change as the ball rotates. Furthermore, we found the shear stress to be asymmetric which can result in significant in-flight torque. Together, asymmetries in force and shear stress produce the complicated flight trajectories that can confound the hapless batter.

  17. Estimating the hydraulic conductivity of slowly permeable and swelling materials from single-ring experiments

    NASA Astrophysics Data System (ADS)

    GéRard-Marchant, P.; Angulo-Jaramillo, R.; Haverkamp, R.; Vauclin, M.; Groenevelt, P.; Elrick, D. E.

    1997-06-01

    The in situ determination of the field-saturated hydraulic conductivity of low-permeability porous materials is a major concern for both geotechnics and soil physics with regards to environmental protection or water resources management. Recent early-time single-ring infiltration experiments, involving sequential constant head and falling head conditions, allow its efficient estimation. Nevertheless, the theory on which the interpretation was based was still strictly valid to nondeformable soils and implicity relied on a particular form of the hydraulic conductivity-soil water pressure head relationship. This theory is now extended to deformable materials, without any restrictive hypothesis. A new concept, bulk sorptivity, which characterizes the solid phase movement, is introduced. Field experiments, conducted on two liners of swelling and slowly permeable materials, revealed that neglecting the soil deformation induces an underestimation of the actual coefficient of permeability of the soil.

  18. Hydrothermal Solidification of Titanium-containing Slowly-cooled Slag with Hydrogarnet Formation

    NASA Astrophysics Data System (ADS)

    Pan, X.; Jing, Z.; Shan, C.; Lu, L.; Zhou, L.

    2010-11-01

    In this study, titanium-containing slowly-cooled slag (TSS) has been solidified hydrothermally under saturated steam pressure at 200° C for 0-24 h. The experimental results showed that additions of NaOH solution and slaked lime could improve the hydraulic activity of TSS effectively, and in turn resulted in a higher strength development. A longer curing time was also found to be favorable to the strength development. The strength enhancement was believed to be due primarily to the formation of hydrogarnet. At 10 mass% slaked lime, 2 M NaOH solution introductions and 12 h curing, the flexural strength of specimens reached 15 MPa, which could be used as construction building materials. Thus, the hydrothermal solidification method may provide a high potential for recycling TSS on a large scale.

  19. Isolated, slowly evolving, and dynamical trapping horizons: Geometry and mechanics from surface deformations

    SciTech Connect

    Booth, Ivan; Fairhurst, Stephen

    2007-04-15

    We study the geometry and dynamics of both isolated and dynamical trapping horizons by considering the allowed variations of their foliating two-surfaces. This provides a common framework that may be used to consider both their possible evolutions and their deformations as well as derive the well-known flux laws. Using this framework, we unify much of what is already known about these objects as well as derive some new results. In particular we characterize and study the 'almost isolated' trapping horizons known as slowly evolving horizons. It is for these horizons that a dynamical first law holds and this is analogous and closely related to the Hawking-Hartle formula for event horizons.

  20. Glucose and cortisol concentrations in cows treated with a slowly-absorbed betamethasone suspension.

    PubMed

    MacDiarmid, S C; Cooper, B S

    1983-01-01

    A slowly-absorbed aqueous suspension of betamethasone, intended for use in the induction;of parturition, was administered to 10 cows. Each cow received 2ml (mean individual dose, 44.4 +/- 0.5microg/kg) by subcutaneous injection. Plasma samples were collected on six occasions over a seven-day period before treatment and on 21 occasions over a 29 day period after treatment. The mean concentration of betamethasone in plasma, as measured by radioimmunoassay, peaked at 0.6ng/ml24 hours after injection and was detectable for four days. Depression of the endogenous cortisol levels, as recorded with other long-acting synthetic glucocorticoids, was observed with this preparation of betamethasone. Plasma glucose was significantly elevated for eight days after betamethasone administration. PMID:16030908

  1. A Nine Month Photometric Study of the Very Slowly Rotating Asteroid 288 Glauke

    NASA Astrophysics Data System (ADS)

    Pilcher, Frederick; Franco, Lorenzo; Pravec, Petr

    2015-01-01

    Fifteen images of the extremely slowly rotating 288 Glauke were obtained every clear night except when the target was very close to the Moon in the interval 2013 Nov. 5 - 2014 July 27 during which the object was more than 60 degrees from the Sun, a total of 187 nights. Tumbling behavior was found, with possible periods near 1170 hours and 740 hours, respectively, and uncertainties probably no larger than 2%. The reliability of tumbling behavior was assessed as PAR=-2. The color index was also determined as V-R=0.48. Magnitude parameters in the V photometric system H=9.99 ± 0.04 and G=0.24 ± 0.02 were found.

  2. First Magnetic Field Models for Recently Discovered Magnetic β Cephei and Slowly Pulsating B Stars

    NASA Astrophysics Data System (ADS)

    Hubrig, S.; Schöller, M.; Ilyin, I.; Briquet, M.; Morel, T.; De Cat, P.

    2012-09-01

    Despite of the importance of magnetic fields for the full understanding of the properties of pulsating β Cephei and slowly pulsating B (SPB) stars, these fields have scarcely been studied over the rotation cycle until now. During the past two years we have obtained multi-epoch polarimetric spectra of several β Cephei and SPB stars with FORS 2 at the Very Large Telescope and SOFIN at the Nordic Optical Telescope to search for a rotation period and to constrain the geometry of the magnetic field. The rotation periods and magnetic field geometries were determined for three β Cephei stars, ℰ1 CMa, 15 CMa, and V1449 Aql, the candidate β Cephei star α Pyx, and the SPB star 33 Eri.

  3. Flow of an elastico-viscous liquid in a curved pipe of slowly varying curvature.

    PubMed

    Sarin, V B

    1993-03-01

    Curvature forms an important feature of thoracic aorta and this paper deals with the flow of an idealized elastico-viscous liquid in a curved pipe of circular cross-section and slowly varying curvature, under a pressure gradient. The flow is assumed to be steady and at low Reynolds numbers. By using the series expansion method of Dean (Phil Mag 4 (1927) 208-223; Phil Mag 5 (1928) 673-693) in powers of a parameter L, which can be considered as the square of ratio of the centrifugal force induced by the circular motion of the fluid to the viscous force, it is shown that in a tube of increasing curvature, there will be delay in setting up of the secondary motion. The wall shear stress, an important parameter in physiological flows, is calculated. The flow of Newtonian fluid in a tube of circular cross section is discussed, as a particular case. PMID:8449591

  4. Creutzfeldt-Jakob Disease Presenting as Progressive Aphasia

    PubMed Central

    Shuttleworth, Edwin C.; Yates, Allan J.; Paltan-Ortiz, Jose D.

    1985-01-01

    The syndrome of slowly progressive aphasia usually has been associated with Pick's disease, Alzheimer's disease, or an isolated focal degenerative disorder of unknown etiology involving the left perisylvian cortex. This report is of a patient with progressive aphasia due to Creutzfeldt-Jakob disease. ImagesFigure 1 PMID:3900429

  5. The tortoise and the hare: slowly evolving T-cell responses take hastily evolving KIR

    PubMed Central

    van Bergen, Jeroen; Koning, Frits

    2010-01-01

    The killer cell immunoglobulin-like receptor (KIR) locus comprises a variable and rapidly evolving set of genes encoding multiple inhibitory and activating receptors. The activating receptors recently evolved from the inhibitory receptors and both bind HLA class I and probably also class I-like structures induced by viral infection. Although generally considered natural killer (NK) cell receptors, KIR are also expressed by a large fraction of effector memory T cells, which slowly accumulate during human life. These effector memory cells are functionally similar to NK cells, as they are immediate effector cells that are cytotoxic and produce IFN-γ. However, different rules apply to NK and T cells with respect to KIR expression and function. For example, KIR tend to modulate signals driven by the T-cell receptor (TCR) rather than to act independently, and use different signal transduction pathways to modulate only a subset of effector functions. The most important difference may lie in the rules governing tolerance: while NK cells with activating KIR binding self-HLA are hyporesponsive, the same is unlikely to apply to T cells. We argue that the expression of activating KIR on virus-specific T cells carrying TCR that weakly cross-react with autoantigens can unleash the autoreactive potential of these cells. This may be the case in rheumatoid arthritis, where cytomegalovirus-specific KIR2DS2+ T cells might cause vasculitis. Thus, the rapid evolution of activating KIR may have allowed for efficient NK-cell control of viruses, but may also have increased the risk that slowly evolving T-cell responses to persistent pathogens derail into autoimmunity. PMID:20722764

  6. Performance of personal inhalable aerosol samplers in very slowly moving air when facing the aerosol source.

    PubMed

    Witschger, O; Grinshpun, S A; Fauvel, S; Basso, G

    2004-06-01

    While personal aerosol samplers have been characterized primarily based on wind tunnel tests conducted at relatively high wind speeds, modern indoor occupational environments are usually represented by very slow moving air. Recent surveys suggest that elevated levels of occupational exposure to inhalable airborne particles are typically observed when the worker, operating in the vicinity of the dust source, faces the source. Thus, the first objective of this study was to design and test a new, low cost experimental protocol for measuring the sampling efficiency of personal inhalable aerosol samplers in the vicinity of the aerosol source when the samplers operate in very slowly moving air. In this system, an aerosol generator, which is located in the centre of a room-sized non-ventilated chamber, continuously rotates and omnidirectionally disperses test particles of a specific size. The test and reference samplers are equally distributed around the source at the same distance from the centre and operate in parallel (in most of our experiments, the total number of simultaneously operating samplers was 15). Radial aerosol transport is driven by turbulent diffusion and some natural convection. For each specific particle size and the sampler, the aerosol mass concentration is measured by weighing the collection filter. The second objective was to utilize the new protocol to evaluate three widely used aerosol samplers: the IOM Personal Inhalable Sampler, the Button Personal Inhalable Aerosol Sampler and the 25 mm Millipore filter holder (closed-face C25 cassette). The sampling efficiencies of each instrument were measured with six particle fractions, ranging from 6.9 to 76.9 micro m in their mass median aerodynamic diameter. The Button Sampler efficiency data demonstrated a good agreement with the standard inhalable convention and especially with the low air movement inhalabilty curve. The 25 mm filter holder was found to considerably under-sample the particles larger

  7. Formation of slowly rotating early-type galaxies via major mergers: a resolution study

    NASA Astrophysics Data System (ADS)

    Bois, M.; Bournaud, F.; Emsellem, E.; Alatalo, K.; Blitz, L.; Bureau, M.; Cappellari, M.; Davies, R. L.; Davis, T. A.; de Zeeuw, P. T.; Duc, P.-A.; Khochfar, S.; Krajnović, D.; Kuntschner, H.; Lablanche, P.-Y.; McDermid, R. M.; Morganti, R.; Naab, T.; Oosterloo, T.; Sarzi, M.; Scott, N.; Serra, P.; Weijmans, A.; Young, L. M.

    2010-08-01

    We study resolution effects in numerical simulations of gas-rich and gas-poor major mergers, and show that the formation of slowly rotating elliptical galaxies often requires a resolution that is beyond the present-day standards to be properly modelled. Our sample of equal-mass merger models encompasses various masses and spatial resolutions, ranging from about 200 pc and 105 particles per component (stars, gas and dark matter), i.e. a gas mass resolution of ~105Msolar, typical of some recently published major merger simulations, to up to 32 pc and ~103Msolar in simulations using 2.4 × 107 collisionless particles and 1.2 × 107 gas particles, among the highest resolutions reached so far for gas-rich major merger of massive disc galaxies. We find that the formation of fast-rotating early-type galaxies, that are flattened by a significant residual rotation, is overall correctly reproduced at all such resolutions. However, the formation of slow-rotating early-type galaxies, which have a low-residual angular momentum and are supported mostly by anisotropic velocity dispersions, is strongly resolution-dependent. The evacuation of angular momentum from the main stellar body is largely missed at standard resolution, and systems that should be slow rotators are then found to be fast rotators. The effect is most important for gas-rich mergers, but is also witnessed in mergers with an absent or modest gas component (0-10 per cent in mass). The effect is robust with respect to our initial conditions and interaction orbits, and originates in the physical treatment of the relaxation process during the coalescence of the galaxies. Our findings show that a high-enough resolution is required to accurately model the global properties of merger remnants and the evolution of their angular momentum. The role of gas-rich mergers of spiral galaxies in the formation of slow-rotating ellipticals may therefore have been underestimated. Moreover, the effect of gas in a galaxy merger is not

  8. Vortex breakdown in a slowly varying tube impulsively rotated about its axis with constant angular velocity

    NASA Astrophysics Data System (ADS)

    MacDonald, D. A.

    2003-11-01

    For time t¯<0 viscous fluid is in slow flow through a long straight axially symmetric tube whose radius, ā(x¯), varies slowly with axial distance, x¯. When t¯=0 the tube is impulsively rotated about its axis with angular velocity, Ω¯, at which angular speed it is thereafter maintained. When Re=Wa/ν=O(1) and ɛ=W¯ā02/νL¯→0, λ=Ωa/W→∞ with Γ=ɛλ2 finite, MacDonald [Phys. Fluids 12, 3168 (2000)] has shown that during the transition from zero angular velocity to solid body rotation the flow in the tube is strikingly different for a diverging and a converging tube, when Γ is sufficiently large. Here, ɛ is the Blasius parameter for slowly varying tubes and ā0 and W denote a reference radius and velocity, respectively. When the tube is diverging, a bubble of recirculating fluid, centered on the axis can occur. This bubble satisfies the definitions of vortex breakdown. When the tube is converging, a toroid of recirculating fluid can occur adjacent to the wall of the tube. Streamlines for each of these cases have been presented [D. A. MacDonald, Phys. Fluids 12, 3168 (2000)]. In this article we shall determine Γ0, the lowest value of Γ for which the toroid will occur, and t¯0, the corresponding instant of time at which it first appears in converging tubes. The wall shear stress is shown to become of large magnitude and graphs of its behavior with x¯/L, where L is a representative length in the axial direction, are presented, when νt¯/ā02=0.1, for representative wall profiles. It is found that incipient flow reversal at the walls of the converging tube ā=(ā0/2)[3-tanh(x¯/L)] occurs at x¯/L=-0.5750, and the critical swirl and the time of occurrence are determined. A figure showing the wall stress against axial distance is also presented for a typical diverging tube when t≡t¯ν/ā02=0.1.

  9. Adult-Onset Asthma to Coronary Heart Disease and Stroke

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Asthma has been associated with atherosclerotic disease in several studies with some evidence that this association may be limited to women. However, most previous studies have failed to account for the heterogeneity of asthma subtypes. We previously reported increased carotid intima medial thickne...

  10. Childhood adversities and adult-onset asthma: a cohort study

    PubMed Central

    Korkeila, Jyrki; Lietzen, Raija; Sillanmäki, Lauri H; Rautava, Päivi; Korkeila, Katariina; Kivimäki, Mika; Koskenvuo, Markku; Vahtera, Jussi

    2012-01-01

    Objectives Childhood adversities may be important determinants of later illnesses and poor health behaviour. However, large-scale prospective studies on the associations between childhood adversities and the onset of asthma in adulthood are lacking. Design Prospective cohort study with 7-year follow-up. Setting Nationally representative study. Data were collected from the Health and Social Support (HeSSup) survey and national registers. Participants The participants represent the Finnish population from the following age groups: 20–24, 30–34, 40–44, and 50–54 years at baseline in 1998 (24 057 survey participants formed the final cohort of this study). The occurrence of childhood adversities was assessed at baseline with a six-item survey scale. The analyses were adjusted for sociodemographic characteristics, behavioural health risks and common mental disorders. Primary and secondary outcomes The survey data were linked to data from national health registers on incident asthma during a 7-year follow-up to define new-onset asthma cases with verified diagnoses. Results A total of 12 126 (59%) participants reported that they encountered a childhood adversity. Of them 3677 (18% of all) endured three to six adversities. During a follow-up of 7 years, 593 (2.9%) participants were diagnosed with incident asthma. Those who reported three or more childhood adversities had a 1.6-fold (95% CI 1.31 to 2.01) greater risk of asthma compared to those without childhood adversities. This hazard attenuated but remained statistically significant after adjustment for conventional risk factors (HR 1.33; 95% CI 1.06 to 1.67). Conclusions Adults who report having encountered adversities in childhood may have an increased risk of developing asthma. PMID:23069774

  11. Adult onset folliculocentric langerhans cell histiocytosis confined to the scalp.

    PubMed

    Hancox, John G; James, Asha Pardasani; Madden, Christopher; Wallace, Christopher A; McMichael, Amy J

    2004-04-01

    Langerhans cell histiocytosis (LCH) is a pleomorphic disease entity characterized by local or disseminated atypical Langerhans cells found most commonly in bone, lungs, mucocutaneous structures, and endocrine organs. Cutaneous disease occurs in approximately one quarter of all cases. Cutaneous findings include soft-tissue swelling, eczematous changes, a seborrheic dermatitis-like appearance, and ulceration. We report a rare case of LCH confined to the scalp with folliculocentric infiltrates. This 32-year-old male patient presented with follicularly based erythema, scale, and pustules unresponsive to topicals and oral antibiotics. The patient's lesions mimicked lichen planopilaris and folliculitis decalvans during the disease process. On hematoxylin and eosin stain, scalp biopsy showed a perivascular interstitial patchy lichenoid mononuclear cell infiltrate that focally abutted follicular infundibula. Prominent mononuclear cells having reniform nuclei were present, and immunoperoxidase stains for CD1a confirmed Langerhans cell differentiation. Serological and imaging workup failed to display systemic involvement. PMID:15024194

  12. Late adult onset of Langerhans cell histiocytosis mimicking glioblastoma multiforme.

    PubMed

    Perren, F; Fankhauser, L; Thiévent, B; Pache, J-C; Delavelle, J; Rochat, T; Landis, T; Chizzolini, C

    2011-02-15

    Langerhans cell histiocytosis (LCH) with multiple organ involvement is a rare disorder in adults. Extrapituitary involvement of the central nervous system (CNS) is uncommon. We report the unusual case of a 55-year-old woman presenting with a left-sided hemiataxia-hemiparesis, left hemisensory loss and short-lasting episodes of an alien left hand due to lesions of the internal capsule and the right thalamus, extending into the mesencephalon associated with extensive surrounding edema, without pituitary involvement. The neuroradiological image suggested glioblastoma multiforme. Brain biopsy revealed inflammatory tissue and "pseudotumoral" multiple sclerosis was suspected. Biopsy of concomitant lung and bone lesions disclosed Langerhans cell histiocytosis. The treatment with pulsed steroids in association with mycophenolate mofetil led to a sustained, clinical neurological remission. PMID:21131007

  13. Clinical analysis of adult-onset spinocerebellar ataxias in Thailand

    PubMed Central

    2014-01-01

    Background Non-ataxic symptoms of spinocerebellar ataxias (SCAs) vary widely and often overlap with various types of SCAs. Duration and severity of the disease and genetic background may play a role in such phenotypic diversity. We conducted the study in order to study clinical characteristics of common SCAs in Thailand and the factors that may influence their phenotypes. Methods 131 (49.43%) out of 265 Thai ataxia families with cerebellar degeneration had positive tests for SCA1, SCA2, Machado-Joseph disease (MJD) or SCA6. The study evaluated 83 available families including SCA1 (21 patients), SCA2 (15), MJD (39) and SCA6 (8). Comparisons of frequency of each non-ataxic sign among different SCA subtypes were analysed. Multivariate logistic regression analyses were undertaken to analyze parameters in association with disease severity and size of CAG repeat. Results Mean ages at onset were not different among patients with different SCAs (40.31 ± 11.33 years, mean ± SD). Surprisingly, SCA6 patients often had age at onset and phenotypes indistinguishable from SCA1, SCA2 and MJD. Frequencies of ophthalmoparesis, nystagmus, hyperreflexia and areflexia were significantly different among the common SCAs, whilst frequency of slow saccade was not. In contrast to Caucasian patients, parkinsonism, dystonia, dementia, and facial fasciculation were uncommon in Thai patients. Multivariate logistic regression analysis demonstrated that ophthalmoparesis (p < 0.001) and sensory impairment (p = 0.025) were associated with the severity of the disease. Conclusions We described clinical characteristics of the 4 most common SCAs in Thailand accounting for almost 90% of familial spinocerebellar ataxias. There were some different observations compared to Caucasian patients including earlier age at onset of SCA6 and the paucity of extrapyramidal features, cognitive impairment and facial fasciculation. Severity of the disease, size of the pathological CAG repeat allele, genetic background and somatic heterogeneity of pathological alleles may influence clinical expressions of these common SCAs. PMID:24708620

  14. Adult-Onset Asthma Might Raise Heart Risks

    MedlinePlus

    ... Heart Risks But shared risk factors, such as air pollution, might explain the connection, researchers say To use ... is often caused by different factors -- such as air pollution -- and often results in a more rapid decline ...

  15. Adult Onset of Xanthelasmoid Mastocytosis: Report of a Rare Entity

    PubMed Central

    Nabavi, Nafiseh Sadat; Nejad, Masumeh Hosseini; Feli, Shahab; Bakhshoodeh, Behnoosh; Layegh, Pouran

    2016-01-01

    Xanthelasmoid or pseudoxanthomatous mastocytosis is an extremely rare variant of diffuse cutaneous mastocytosis. Herein, we describe an adult male with cutaneous mastocytosis showing multiple widespread yellowish ovoid papules like eruptive xanthoma. A 60-year-old male visited our outpatient clinic with a 1-year history of generalized yellowish, ovoid, and skin color papular eruption located on the trunk, groin, extremities, with the modest pruritus. Vital signs were stable, and Darier's sign was negative. No other subjective and objective signs were detected during the examination. No abnormality was detected in his diagnostic laboratory tests. Skin biopsy was taken, and histopathologic examination revealed proliferation of mast cells with ovoid and spindle nuclei with distinct cytoplasm borders around the capillaries, which was compatible with mastocytosis. Antihistamine was prescribed for pruritus control which was successful, but eruptions were persistent, and even 1-year phototherapy was not useful. PMID:27512209

  16. Recurrent adult onset Henoch-Schonlein Purpura: a case report.

    PubMed

    Gaskill, Neil; Guido, Bruce; Mago, Cynthia

    2016-01-01

    Henoch-Schonlein purpura is an immunoglobulin A (IgA)-immune complex mediated leukocytoclastic vasculitis that classically manifests with palpable purpura, abdominal pain, arthritis, and hematuria or proteinuria. The condition is much more predominant in children (90% of cases) and commonly follows an upper respiratory infection. We present a case of recurrent Henoch-Schonlein purpura (HSP) complicated by nephritis in an adult female initially categorized as IgA nephropathy (IgAN). We review the pathophysiologic basis of HSP nephritis as the variant of HSP accompanied by renal involvement and its pathogenetic commonality with IgA nephropathy. PMID:27617937

  17. Nonexponential decay of room-temperature phosphorescence: evidence for several slowly interconverting or static protein conformers

    NASA Astrophysics Data System (ADS)

    Schlyer, Bruce D.; Schauerte, Joseph A.; Steel, Duncan G.; Gafni, Ari

    1994-08-01

    The phosphorescence decays of horse liver alcohol dehydrogenase (LADH) Trp314, E. coli alkaline phosphatase (AP) Trp109, and B. stearothermophilus phosphofructokinase (PFK) Trp179 are decidedly nonexponential at room temperature. When the data is analyzed using the maximum entropy method (MEM) the AP phosphorescence decay is dominated by a single gaussian distribution while for LADH and PFK the data reveals at least two amplitude packets. The MEM lifetime-normalized widths for these proteins are significantly larger than obtained for the model monoexponential chromophore terbium suggesting that the complex kinetics is intrinsic to the protein. Since the phosphorescence lifetime of a tryptophan residue is related to its microviscosity, the nonexponential decay behavior may imply that the phosphorescing tryptophan residue in each of these samples is best described as existing in at least two states of different local rigidity which interconvert more slowly than the time scale of the phosphorescence decay (0.1 to 1.0 sec). The existence of multiple, long-lived, conformers is further supported by the observation that the phosphorescence lifetime in the LADH sample is excitation wavelength dependent.

  18. Slowly rotating neutron stars in scalar-tensor theories with a massive scalar field

    NASA Astrophysics Data System (ADS)

    Yazadjiev, Stoytcho S.; Doneva, Daniela D.; Popchev, Dimitar

    2016-04-01

    In the scalar-tensor theories with a massive scalar field, the coupling constants, and the coupling functions in general, which are observationally allowed, can differ significantly from those in the massless case. This fact naturally implies that the scalar-tensor neutron stars with a massive scalar field can have rather different structure and properties in comparison with their counterparts in the massless case and in general relativity. In the present paper, we study slowly rotating neutron stars in scalar-tensor theories with a massive gravitational scalar. Two examples of scalar-tensor theories are examined—the first example is the massive Brans-Dicke theory and the second one is a massive scalar-tensor theory indistinguishable from general relativity in the weak-field limit. In the latter case, we study the effect of the scalar field mass on the spontaneous scalarization of neutron stars. Our numerical results show that the inclusion of a mass term for the scalar field indeed changes the picture drastically compared to the massless case. It turns out that mass, radius, and moment of inertia for neutron stars in massive scalar-tensor theories can differ drastically from the pure general relativistic solutions if sufficiently large masses of the scalar field are considered.

  19. A cyclostrophic transformed Eulerian zonal mean model for the middle atmosphere of slowly rotating planets

    NASA Astrophysics Data System (ADS)

    Li, King-Fai; Yao, Kaixuan; Taketa, Cameron; Zhang, Xi; Liang, Mao-Chang; Jiang, Xun; Newman, Claire; Tung, Ka-Kit; Yung, Yuk L.

    2016-04-01

    With the advance of modern computers, studies of planetary atmospheres have heavily relied on general circulation models (GCMs). Because these GCMs are usually very complicated, the simulations are sometimes difficult to understand. Here we develop a semi-analytic zonally averaged, cyclostrophic residual Eulerian model to illustrate how some of the large-scale structures of the middle atmospheric circulation can be explained qualitatively in terms of simple thermal (e.g. solar heating) and mechanical (the Eliassen-Palm flux divergence) forcings. This model is a generalization of that for fast rotating planets such as the Earth, where geostrophy dominates (Andrews and McIntyre 1987). The solution to this semi-analytic model consists of a set of modified Hough functions of the generalized Laplace's tidal equation with the cyclostrohpic terms. As an example, we apply this model to Titan. We show that the seasonal variations of the temperature and the circulation of these slowly-rotating planets can be well reproduced by adjusting only three parameters in the model: the Brunt-Väisälä bouyancy frequency, the Newtonian radiative cooling rate, and the Rayleigh friction damping rate. We will also discuss an application of this model to study the meridional transport of photochemically produced tracers that can be observed by space instruments.

  20. Asteroseismic Fingerprints of Rotation and Mixing in the Slowly Pulsating B8 V Star KIC 7760680

    NASA Astrophysics Data System (ADS)

    Pápics, P. I.; Tkachenko, A.; Aerts, C.; Van Reeth, T.; De Smedt, K.; Hillen, M.; Østensen, R.; Moravveji, E.

    2015-04-01

    We present the first detection of a rotationally affected series consisting of 36 consecutive high-order sectoral dipole gravity modes in a slowly pulsating B (SPB) star. The results are based on the analysis of four years of virtually uninterrupted photometric data assembled with the Kepler Mission, and high-resolution spectra acquired using the HERMES spectrograph at the 1.2 m Mercator Telescope. The specroscopic measurements place KIC 7760680 inside the SPB instability strip, near the cool edge, given its fundamental parameters of {{T}eff}=11650+/- 210 K, log g=3.97+/- 0.08 dex, microturbulent velocity {{ξ }t}=0.0-0.0+0.6 km {{s}-1}, vsin i=61.5+/- 5.0 km {{s}-1}, and [M/H]=0.14+/- 0.09 dex. The photometric analysis reveals the longest unambiguous series of gravity modes of the same degree \\ell with consecutive radial order n, which carries clear signatures of chemical mixing and rotation. With such exceptional observational constraints, this star should be considered as the Rosetta stone of SPBs for future modeling, and brings us a step closer to the much-needed seismic calibration of stellar structure models of massive stars.

  1. Designed amphiphilic peptide forms stable nanoweb, slowly releases encapsulated hydrophobic drug, and accelerates animal hemostasis

    PubMed Central

    Ruan, Liping; Zhang, Hangyu; Luo, Hanlin; Liu, Jingping; Tang, Fushan; Shi, Ying-Kang; Zhao, Xiaojun

    2009-01-01

    How do you design a peptide building block to make 2-dimentional nanowebs and 3-dimensional fibrous mats? This question has not been addressed with peptide self-assembling nanomaterials. This article describes a designed 9-residue peptide, N-Pro-Ser-Phe-Cys-Phe-Lys-Phe-Glu-Pro-C, which creates a strong fishnet-like nanostructure depending on the peptide concentrations and mechanical disruptions. This peptide is intramolecularly amphiphilic because of a single pair of ionic residues, Lys and Glu, at one end and nonionic residues, Phe, Cys, and Phe, at the other end. Circular dichroism and Fourier transform infrared spectroscopy analysis demonstrated that this peptide adopts stable β-turn and β-sheet structures and self-assembles into hierarchically arranged supramolecular aggregates in a concentration-dependent fashion, demonstrated by atomic force microscopy and electron microscopy. At high concentrations, the peptide dominantly self-assembled into globular aggregates that were extensively connected with each other to form “beads-on-a-thread” type nanofibers. These long nanofibers were extensively branched and overlapped to form a self-healing peptide hydrogel consisting of >99% water. This peptide can encapsulate the hydrophobic model drug pyrene and slowly release pyrene from coated microcrystals to liposomes. It can effectively stop animal bleeding within 30 s. We proposed a plausible model to interpret the intramolecular amphiphilic self-assembly process and suggest its importance for the future development of new biomaterials for drug delivery and regenerative medicine. PMID:19289834

  2. Computation identifies structural features that govern neuronal firing properties in slowly adapting touch receptors

    PubMed Central

    Lesniak, Daine R; Marshall, Kara L; Wellnitz, Scott A; Jenkins, Blair A; Baba, Yoshichika; Rasband, Matthew N; Gerling, Gregory J; Lumpkin, Ellen A

    2014-01-01

    Touch is encoded by cutaneous sensory neurons with diverse morphologies and physiological outputs. How neuronal architecture influences response properties is unknown. To elucidate the origin of firing patterns in branched mechanoreceptors, we combined neuroanatomy, electrophysiology and computation to analyze mouse slowly adapting type I (SAI) afferents. These vertebrate touch receptors, which innervate Merkel cells, encode shape and texture. SAI afferents displayed a high degree of variability in touch-evoked firing and peripheral anatomy. The functional consequence of differences in anatomical architecture was tested by constructing network models representing sequential steps of mechanosensory encoding: skin displacement at touch receptors, mechanotransduction and action-potential initiation. A systematic survey of arbor configurations predicted that the arrangement of mechanotransduction sites at heminodes is a key structural feature that accounts in part for an afferent’s firing properties. These findings identify an anatomical correlate and plausible mechanism to explain the driver effect first described by Adrian and Zotterman. DOI: http://dx.doi.org/10.7554/eLife.01488.001 PMID:24448409

  3. Preparation of slowly digestible sweet potato Daeyumi starch by dual enzyme modification.

    PubMed

    Jo, A Ra; Kim, Ha Ram; Choi, Seung Jun; Lee, Joon Seol; Chung, Mi Nam; Han, Seon Kyeong; Park, Cheon-Seok; Moon, Tae Wha

    2016-06-01

    Sweet potato Daeyumi starch was dually modified using glycogen branching enzyme (BE) from Streptococcus mutans and amylosucrase (AS) from Neisseria polysaccharea to prepare slowly digestible starch (SDS). Dually modified starches had higher SDS and resistant starch (RS) contents than control starch. The branched chain length distributions of the BE-modified starches indicated an increase in short side-chains [degree of polymerization (DP)≤12] compared with native starch. AS treatment of the BE-modified starches decreased the proportion of short side-chains and increased the proportion of long side-chains (DP≥25) and molecular mass. It also resulted in a B-type X-ray diffraction pattern and an increased relative crystallinity. Regarding thermal properties, the BE-modified starches showed no endothermic peak, whereas the BEAS-modified starches had a broader melting temperature range and lower melting enthalpy compared to native starch. The combined enzymatic treatment resulted in novel glucan polymers with slow digestion properties. PMID:27083356

  4. Effect of electron temperature fluctuations on slowly swept Langmuir probe measurements

    SciTech Connect

    Rudakov, D.L.; Boedo, J.A.; Moyer, R.A.; Stangeby, P.C.; McLean, A.; Watkins, J.G.

    2004-10-01

    Swept Langmuir probes are widely used to measure electron temperature (T{sub e}) in laboratory plasmas by performing an exponential fit to the measured volt-ampere (I-V) characteristic. Often the probe voltage sweep frequency is much lower than the characteristic frequencies of the plasma fluctuations and a time-averaged I-V characteristic is used for the fit. We show by numerical modeling that in the presence of T{sub e} fluctuations with frequencies well above the voltage sweep frequency this standard technique applied to a swept single probe tends to read higher than the actual time-averaged T{sub e} provided no correlated plasma potential (V{sub p}) fluctuations are present. In the presence of coupled T{sub e} and V{sub p} fluctuations a slowly swept single probe may read either higher or lower than the average T{sub e}, depending on the relative amplitude and phase of the temperature and potential fluctuations. In contrast, swept double probe measurements of T{sub e} are virtually unaffected by either T{sub e} or V{sub p} fluctuations.

  5. Magnetic field geometries of two slowly rotating Ap/Bp stars: HD 12288 and HD 14437

    NASA Astrophysics Data System (ADS)

    Wade, G. A.; Kudryavtsev, D.; Romanyuk, I. I.; Landstreet, J. D.; Mathys, G.

    2000-03-01

    In this paper we report magnetic field models and basic physical parameters for the slowly rotating Ap/Bp stars HD 12288 and HD 14437. Using new and previously published mean longitudinal magnetic field, mean magnetic field modulus, and hipparcos photometric measurements, we have inferred the rotational periods of both stars (HD 12288: P_rot=34.9d +/- 0.2d HD 14437: P_rot=26.87d +/- 0.02d). From the magnetic measurements we have determined the best-fit decentred magnetic dipole configurations. For HD 12288, we find that the field geometry is consistent with a centred dipole, while for HD 14437 a large decentring parameter (a=0.23 R_*) is inferred. Both stars show one angle in the ambiguous (i,beta ) couplet which is smaller than about 20degr . This is consistent with the observation of Landstreet & Mathys (2000), who point out that almost all magnetic Ap stars with periods longer than about 30 days exhibit magnetic fields aligned with their rotational axis.

  6. Transport of Brownian particles in a narrow, slowly varying serpentine channel

    NASA Astrophysics Data System (ADS)

    Wang, Xinli; Drazer, German

    2015-04-01

    We study the transport of Brownian particles under a constant driving force and moving in channels that present a varying centerline but have constant aperture width (serpentine channels). We investigate two types of channels, solid channels, in which the particles are geometrically confined between solid walls and soft channels, in which the particles are confined by the potential energy landscape. We consider the limit of narrow, slowly varying channels, i.e., when the aperture and the variation in the position of the centerline are small compared to the length of a unit cell in the channel (wavelength). We use the method of asymptotic expansions to determine both the average velocity (or mobility) and the effective dispersion coefficient of the particles. We show that both solid and soft-channels have the same effects on the transport properties up to leading order correction. Including the next order correction, we obtain that the mobility in a solid-channel is smaller than that in a soft-channel. However, we discuss an alternative definition of the effective width of a soft channel that leads to equal mobilities up to second order terms. Interestingly, in both cases, the corrections to the mobility of the particles are independent of the Péclet number, and the Einstein-Smoluchowski relation is satisfied.

  7. Identification of pulsational modes in rotating slowly pulsating B-type stars

    NASA Astrophysics Data System (ADS)

    Szewczuk, W.; Daszyńska-Daszkiewicz, J.

    2015-06-01

    Knowledge of the geometry of pulsational modes is a prerequisite for seismic modelling of stars. In the case of slowly pulsating B-type (SPB) pulsators, the simple zero-rotation approach so far used for mode identification is usually not valid because pulsational frequencies are often of the order of the rotational frequency. Moreover, this approach allows us to determine only the spherical harmonic degree, ℓ, while the azimuthal order, m, is beyond its reach. On the other hand, because of the density of oscillation spectra of SPB stars, knowledge of m is indispensable if one wants to assign the radial order, n, to the observed frequency peaks. Including the effects of rotation via the traditional approximation, we perform identification of the mode angular numbers (ℓ, m) for 31 SPB stars with available multicolour time series photometry. Simultaneously, constraints on the rotational velocity, Vrot, and the inclination angle, i, are determined assuming uniform rotation and a constant value of Vrot sin i. Dependence of the results on the adopted model is tested using HD 21071 as an example. Despite some model uncertainties and limitations of the method, our studies show the correct approach to identifying the low-frequency oscillation modes.

  8. Work statistics of charged noninteracting fermions in slowly changing magnetic fields.

    PubMed

    Yi, Juyeon; Talkner, Peter

    2011-04-01

    We consider N fermionic particles in a harmonic trap initially prepared in a thermal equilibrium state at temperature β^{-1} and examine the probability density function (pdf) of the work done by a magnetic field slowly varying in time. The behavior of the pdf crucially depends on the number of particles N but also on the temperature. At high temperatures (β≪1) the pdf is given by an asymmetric Laplace distribution for a single particle, and for many particles it approaches a Gaussian distribution with variance proportional to N/β(2). At low temperatures the pdf becomes strongly peaked at the center with a variance that still linearly increases with N but exponentially decreases with the temperature. We point out the consequences of these findings for the experimental confirmation of the Jarzynski equality such as the low probability issue at high temperatures and its solution at low temperatures, together with a discussion of the crossover behavior between the two temperature regimes. PMID:21599127

  9. Evidence for a slowly exchangeable pool of calcium in the pancreatic beta cell plasma membrane.

    PubMed Central

    Gylfe, E; Hellman, B

    1982-01-01

    1. Exposure to media deprived of Ca2+ resulted in prompt and transient stimulation of 45Ca efflux from beta cell-rich pancreatic islets microdissected from ob/ob-mice and to some extent also from the isolated neurohypophysis. 2. Particular high efflux rates were reached when the Ca2+-deficient medium contained EGTA, but there was no effect of the chelator on the total amount of radioactivity mobilized from the islets. 3. The removal of extracellular Ca2+ was less effective in promoting the 45Ca efflux in the absence of Na+ and no stimulatory response was seen in the presence of 1 mM-La3+. 4. The 45Ca washout was stimulated whether or not the media used for the loading or subsequent perifusion of the islets were supplemented with 20 mM-D-glucose. However, there was no response to a second exposure to a Ca2+-deficient medium even subsequent to redistribution of intracellular calcium induced by temporary lowering of the temperature. 5. It is suggested that the islet 45Ca released by the removal of extracellular Ca2+ originates from a distinct plasma membrane pool which is exchanged slowly compared to most of the calcium at the beta cell periphery. PMID:6752376

  10. Computation identifies structural features that govern neuronal firing properties in slowly adapting touch receptors.

    PubMed

    Lesniak, Daine R; Marshall, Kara L; Wellnitz, Scott A; Jenkins, Blair A; Baba, Yoshichika; Rasband, Matthew N; Gerling, Gregory J; Lumpkin, Ellen A

    2014-01-01

    Touch is encoded by cutaneous sensory neurons with diverse morphologies and physiological outputs. How neuronal architecture influences response properties is unknown. To elucidate the origin of firing patterns in branched mechanoreceptors, we combined neuroanatomy, electrophysiology and computation to analyze mouse slowly adapting type I (SAI) afferents. These vertebrate touch receptors, which innervate Merkel cells, encode shape and texture. SAI afferents displayed a high degree of variability in touch-evoked firing and peripheral anatomy. The functional consequence of differences in anatomical architecture was tested by constructing network models representing sequential steps of mechanosensory encoding: skin displacement at touch receptors, mechanotransduction and action-potential initiation. A systematic survey of arbor configurations predicted that the arrangement of mechanotransduction sites at heminodes is a key structural feature that accounts in part for an afferent's firing properties. These findings identify an anatomical correlate and plausible mechanism to explain the driver effect first described by Adrian and Zotterman. DOI: http://dx.doi.org/10.7554/eLife.01488.001. PMID:24448409

  11. Slowly rotating anisotropic neutron stars in general relativity and scalar-tensor theory

    NASA Astrophysics Data System (ADS)

    Silva, Hector O.; Macedo, Caio F. B.; Berti, Emanuele; Crispino, Luís C. B.

    2015-07-01

    Some models (such as the Skyrme model, a low-energy effective field theory for quantum chromodynamics) suggest that the high-density matter prevailing in neutron star (NS) interiors may be significantly anisotropic. Anisotropy is known to affect the bulk properties of nonrotating NSs in general relativity (GR). In this paper we study the effects of anisotropy on slowly rotating stars in GR. We also consider one of the most popular extensions of Einstein’s theory, namely scalar-tensor theories allowing for spontaneous scalarization (a phase transition similar to spontaneous magnetization in ferromagnetic materials). Anisotropy affects the moment of inertia of NSs (a quantity that could potentially be measured in binary pulsar systems) in both theories. We find that the effects of scalarization increase (decrease) when the tangential pressure is bigger (smaller) than the radial pressure, and we present a simple criterion to determine the onset of scalarization by linearizing the scalar-field equation. Our calculations suggest that binary pulsar observations may constrain the degree of anisotropy or even, more optimistically, provide evidence for anisotropy in NS cores.

  12. Conditions for the formation of nongyrotropic current sheets in slowly evolving plasmas

    NASA Astrophysics Data System (ADS)

    Schindler, Karl; Hesse, Michael

    2010-08-01

    This paper addresses the formation of nongyrotropic current sheets resulting from slow external driving. The medium is a collisionless plasma with one spatial dimension and a three-dimensional velocity space. The study is based on particle simulation and an analytical approach. Earlier results that apply to compression of an initial Harris sheet are generalized in several ways. In a first step a general sufficient criterion for the presence of extra ion and electron currents due to nongyrotropic plasma conditions is derived. Then cases with antisymmetric magnetic and electric fields are considered. After establishing consistency of the criterion with the earlier case, the usefulness of this concept is illustrated in detail by two further particle simulations. The results indicate that the formation of nongyrotropic current sheets is a ubiquitous phenomenon for plasmas with antisymmetric fields that have evolved slowly from initial gyrotropic states. A fourth case concerns a plasma with a unidirectional magnetic field. Consistent with the general criterion, the observed final state is fluidlike in that it is approximately gyrotropic. Momentum balance is shown to include a contribution that results from accumulation of an off-diagonal pressure tensor component during the evolution. Heat flux also plays an important role.

  13. Adaptive compression of slowly varying images transmitted over Wireless Sensor Networks.

    PubMed

    Nikolakopoulos, George; Kandris, Dionisis; Tzes, Anthony

    2010-01-01

    In this article a scheme for image transmission over Wireless Sensor Networks (WSN) with an adaptive compression factor is introduced. The proposed control architecture affects the quality of the transmitted images according to: (a) the traffic load within the network and (b) the level of details contained in an image frame. Given an approximate transmission period, the adaptive compression mechanism applies Quad Tree Decomposition (QTD) with a varying decomposition compression factor based on a gradient adaptive approach. For the initialization of the proposed control scheme, the desired a priori maximum bound for the transmission time delay is being set, while a tradeoff among the quality of the decomposed image frame and the time needed for completing the transmission of the frame should be taken under consideration. Based on the proposed control mechanism, the quality of the slowly varying transmitted image frames is adaptively deviated based on the measured time delay in the transmission. The efficacy of the adaptive compression control scheme is validated through extended experimental results. PMID:22163598

  14. The structure and function of a slowly adapting touch corpuscle in hairy skin

    PubMed Central

    Iggo, A.; Muir, A. R.

    1969-01-01

    1. Slowly adapting cutaneous mechanoreceptors, in the cat and primates, have been studied by histological and neurophysiological methods. 2. Each touch corpuscle is a dome-shaped elevation of the epidermis, whose deepest layer contains up to fifty specialized tactile cells. 3. Nerve plates, enclosed by the tactile cell (Merkel cells), are connected to a single myelinated axon in the dense collagenous core of the corpuscle. 4. The corpuscle generated > 1000 impulses/sec when excited by vertical surface pressure. The response was highly localized and showed a low mechanical threshold, the frequency being dependent upon the velocity and amplitude of the displacement. There was a period of rapid adaptation before a sustained response which might continue for > 30 min. 5. A quantitative analysis of the responses to excitation by displacements of differing amplitude, velocity and duration is included. 6. The discharge of touch corpuscle units evoked by a mechanical stimulus was temperature-sensitive, and was enhanced by a fall in skin temperature. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11 PMID:4974746

  15. DISCOVERY OF 14 NEW SLOWLY PULSATING B STARS IN THE OPEN CLUSTER NGC 7654

    SciTech Connect

    Luo, Y. P.; Han, Z. W.

    2012-02-10

    We carried out time-series BV CCD photometric observations of the open cluster NGC 7654 (Messier 52) to search for variable stars. Eighteen slowly pulsating B (SPB) stars have been detected, among which 14 candidates are newly discovered, three known ones are confirmed, and a previously found {delta} Scuti star is also identified as an SPB candidate. Twelve SPBs are probable cluster members based on membership analysis. This makes NGC 7654 the richest galactic open cluster in terms of SPB star content. It is also a new discovery that NGC 7654 hosts three {gamma} Dor star candidates. We found that all these stars (18 SPB and 3 {gamma} Dor stars) have periods longer than their corresponding fundamental radial mode. With such a big sample of g-mode pulsators in a single cluster, it is clear that multi-mode pulsation is more common in the upper part of the main sequence than in the lower part. All the stars span a narrow strip on the period-luminosity plane, which also includes the {gamma} Dor stars at the low-luminosity extension. This result implies that there may be a single period-luminosity relation applicable to all g-mode main-sequence pulsators. As a by-product, three EA-type eclipsing binaries and an EW-type eclipsing binary are also discovered.

  16. Slowly varying function method applied to quartz crystal oscillator transient calculation.

    PubMed

    Brendel, R; Ratier, N; Couteleau, L; Marianneau, G; Guillemot, P

    1998-01-01

    By using an approach based on the full nonlinear Barkhausen criterion, it is possible to describe oscillator behavior under the form of a nonlinear characteristic polynomial whose coefficients are functions of the circuit components and of the oscillation amplitude. Solving the polynomial in the frequency domain leads to the steady state oscillation amplitude and frequency. In the time domain, the characteristic polynomial represents a nonlinear differential equation whose solution gives the oscillator signal transient. It is shown how symbolic manipulation capabilities of commercially available softwares can be used to automatically generate the coding of the oscillator characteristic polynomial from the SPICE description netlist. The numerical processing of such an equation in the time domain leads to unacceptable computer time because of the high quality factor of the oscillator circuits involved. Nevertheless, by using the slowly varying amplitude and phase method, it is possible to transform the initial nonlinear differential equation into a nonlinear first order differential equation system in the amplitude and phase variables. The solution of this system directly gives the designer the most relevant features of the oscillation; that is, the amplitude, phase, or frequency transients which can be accurately obtained within a short computer time by using classical numerical algorithms. PMID:18244202

  17. Augmented brain function by coordinated reset stimulation with slowly varying sequences

    PubMed Central

    Zeitler, Magteld; Tass, Peter A.

    2015-01-01

    Several brain disorders are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR) stimulation was developed to selectively counteract abnormal neuronal synchrony by desynchronization. For this, phase resetting stimuli are delivered to different subpopulations in a timely coordinated way. In neural networks with spike timing-dependent plasticity CR stimulation may eventually lead to an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and abnormal synchrony. The spatiotemporal sequence by which all stimulation sites are stimulated exactly once is called the stimulation site sequence, or briefly sequence. So far, in simulations, pre-clinical and clinical applications CR was applied either with fixed sequences or rapidly varying sequences (RVS). In this computational study we show that appropriate repetition of the sequence with occasional random switching to the next sequence may significantly improve the anti-kindling effect of CR. To this end, a sequence is applied many times before randomly switching to the next sequence. This new method is called SVS CR stimulation, i.e., CR with slowly varying sequences. In a neuronal network with strong short-range excitatory and weak long-range inhibitory dynamic couplings SVS CR stimulation turns out to be superior to CR stimulation with fixed sequences or RVS. PMID:25873867

  18. Mean apical concentration and duration in the comparative bioavailability of slowly absorbed and eliminated drug preparations.

    PubMed

    Pollak, P T; Freeman, D J; Carruthers, S G

    1988-06-01

    Present criteria for comparing bioavailability are inadequate when the Cmax and tmax cannot be reliably identified in individual subjects. Drug formulations which are slowly absorbed and eliminated have concentration-time profiles with a broad apex, increasing the likelihood that samples taken at the apical region of the curve will have statistically indistinguishable concentrations. Using data from a study of three dosage forms of piroxicam, we propose an alternative approach which decreases the influence of sampling bias and analytical error on the identification of the apex of the concentration-time curve and provides a simple tool for describing the shape of the curve around the apex. An adequate frequency of sampling around the expected apex of the concentration-time curve and consideration of the coefficient of variation (CV) of the analytical assay when assessing the observed Cmax are used in defining new parameters. This approach may be useful for studying the relationship of onset and duration of maximal plasma concentration to the efficacy and toxicity of drugs and in developing standards for comparing the bioavailability of slow-release preparations, which is of increasing interest to pharmaceutical companies and regulatory agencies. PMID:3171924

  19. The Bayesian Decoding of Force Stimuli from Slowly Adapting Type I Fibers in Humans

    PubMed Central

    Wright, James; Khamis, Heba; Birznieks, Ingvars; van Schaik, André

    2016-01-01

    It is well known that signals encoded by mechanoreceptors facilitate precise object manipulation in humans. It is therefore of interest to study signals encoded by the mechanoreceptors because this will contribute further towards the understanding of fundamental sensory mechanisms that are responsible for coordinating force components during object manipulation. From a practical point of view, this may suggest strategies for designing sensory-controlled biomedical devices and robotic manipulators. We use a two-stage nonlinear decoding paradigm to reconstruct the force stimulus given signals from slowly adapting type one (SA-I) tactile afferents. First, we describe a nonhomogeneous Poisson encoding model which is a function of the force stimulus and the force’s rate of change. In the decoding phase, we use a recursive nonlinear Bayesian filter to reconstruct the force profile, given the SA-I spike patterns and parameters described by the encoding model. Under the current encoding model, the mode ratio of force to its derivative is: 1.26 to 1.02. This indicates that the force derivative contributes significantly to the rate of change to the SA-I afferent spike modulation. Furthermore, using recursive Bayesian decoding algorithms is advantageous because it can incorporate past and current information in order to make predictions—consistent with neural systems—with little computational resources. This makes it suitable for interfacing with prostheses. PMID:27077750

  20. Asymptotic analysis of the density of states in random matrix models associated with a slowly decaying weight

    NASA Astrophysics Data System (ADS)

    Kuijlaars, A. B. J.

    2001-08-01

    The asymptotic behavior of polynomials that are orthogonal with respect to a slowly decaying weight is very different from the asymptotic behavior of polynomials that are orthogonal with respect to a Freud-type weight. While the latter has been extensively studied, much less is known about the former. Following an earlier investigation into the zero behavior, we study here the asymptotics of the density of states in a unitary ensemble of random matrices with a slowly decaying weight. This measure is also naturally connected with the orthogonal polynomials. It is shown that, after suitable rescaling, the weak limit is the same as the weak limit of the rescaled zeros.

  1. Progressive bilateral thinning of the parietal bones

    SciTech Connect

    Cederlund, C.G.; Andren, L.; Olivecrona, H.

    1982-03-01

    Observation of a case of progressive bilateral parietal thinning within a period of 14 years induced us to study skull films of 3 636 consecutive patients. Parietal thinning was found in 86 patients (2.37%). It was more common in women, with a sex ratio of 1:1.9. The mean age of the females was 72 years, and that of the males 63 years. Previous skull films of 25 of these patients were available and showed progression in 10. It is concluded that parietal thinning is a slowly progressive disease of middle-aged and old patients and is not an anatomical variant or congenital dysplasia of the dipole.

  2. Slowly fading super-luminous supernovae that are not pair-instability explosions.

    PubMed

    Nicholl, M; Smartt, S J; Jerkstrand, A; Inserra, C; McCrum, M; Kotak, R; Fraser, M; Wright, D; Chen, T-W; Smith, K; Young, D R; Sim, S A; Valenti, S; Howell, D A; Bresolin, F; Kudritzki, R P; Tonry, J L; Huber, M E; Rest, A; Pastorello, A; Tomasella, L; Cappellaro, E; Benetti, S; Mattila, S; Kankare, E; Kangas, T; Leloudas, G; Sollerman, J; Taddia, F; Berger, E; Chornock, R; Narayan, G; Stubbs, C W; Foley, R J; Lunnan, R; Soderberg, A; Sanders, N; Milisavljevic, D; Margutti, R; Kirshner, R P; Elias-Rosa, N; Morales-Garoffolo, A; Taubenberger, S; Botticella, M T; Gezari, S; Urata, Y; Rodney, S; Riess, A G; Scolnic, D; Wood-Vasey, W M; Burgett, W S; Chambers, K; Flewelling, H A; Magnier, E A; Kaiser, N; Metcalfe, N; Morgan, J; Price, P A; Sweeney, W; Waters, C

    2013-10-17

    Super-luminous supernovae that radiate more than 10(44) ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae. Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of (56)Ni are synthesized; this isotope decays to (56)Fe via (56)Co, powering bright light curves. Such massive progenitors are expected to have formed from metal-poor gas in the early Universe. Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova. Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae, which are not powered by radioactivity. Modelling our observations with 10-16 solar masses of magnetar-energized ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 × 10(-6) times that of the core-collapse rate. PMID:24132291

  3. Optimizing Electrospray Interfaces Using Slowly Diverging Conical Duct (ConDuct) Electrodes

    PubMed Central

    Krutchinsky, Andrew N.; Padovan, Júlio C.; Cohen, Herbert; Chait, Brian T.

    2015-01-01

    We demonstrate that the efficiency of ion transmission from atmosphere to vacuum through stainless steel electrodes that contain slowly divergent conical duct (ConDuct) channels can be close to 100%. Here, we explore the properties of 2.5 cm long electrodes with angles of divergence of 0°, 1°, 2°, 3°, 5°, 8°, 13°, and 21°, respectively. The ion transmission efficiency was observed to jump from 10–20% for the 0° (straight) channels to 90–95% for channels with an angle of divergence as small as 1°. Furthermore, the 2–3° ConDuct electrodes produced extraordinarily low divergence ion beams that propagated in a laser-like fashion over long distances in vacuum. To take advantage of these newly discovered properties, we constructed a novel atmosphere-to-vacuum ion interface utilizing a 2° ConDuct as an inlet electrode and compared its ion transmission efficiency with that of the interface used in the commercial (Thermo) Velos Orbitrap and Q Exactive mass spectrometers. We observed that the ConDuct interface transmitted up to 17 times more ions than the commercial reference interface and also yielded improved signal-to-noise mass spectra of peptides. We infer from these results that the performance of many current atmosphere-tovacuum interfaces utilizing metal capillaries can be substantially improved by replacing them with 1° or 2° metal ConDuct electrodes, which should preserve the convenience of supplying ion desolvation energy by heating the electrode while greatly increasing the efficiency of ion transmission into the mass spectrometer. PMID:25667060

  4. Slowly emerging glycinergic transmission enhances inhibition in the sound localization pathway of the avian auditory system

    PubMed Central

    Fischl, Matthew J.; Weimann, Sonia R.; Kearse, Michael G.

    2013-01-01

    Localization of low-frequency acoustic stimuli is processed in dedicated neural pathways where coincidence-detecting neurons compare the arrival time of sound stimuli at the two ears, or interaural time disparity (ITD). ITDs occur in the submillisecond range, and vertebrates have evolved specialized excitatory and inhibitory circuitry to compute these differences. Glycinergic inhibition is a computationally significant and prominent component of the mammalian ITD pathway. However, evidence for glycinergic transmission is limited in birds, where GABAergic inhibition has been thought to be the dominant or exclusive inhibitory transmitter. Indeed, previous work showed that GABA antagonists completely eliminate inhibition in avian nuclei specialized for processing temporal features of sound, nucleus magnocellularis (NM) and nucleus laminaris (NL). However, more recent work shows that glycine is coexpressed with GABA in synaptic terminals apposed to neurons in both nuclei (Coleman WL, Fischl MJ, Weimann SR, Burger RM. J Neurophysiol 105: 2405–2420, 2011; Kuo SP, Bradley LA, Trussell LO. J Neurosci 29: 9625–9634, 2009). Here we show complementary evidence of functional glycine receptor (GlyR) expression in NM and NL. Additionally, we show that glycinergic input can be evoked under particular stimulus conditions. Stimulation at high but physiologically relevant rates evokes a slowly emerging glycinergic response in NM and NL that builds over the course of the stimulus. Glycinergic response magnitude was stimulus rate dependent, representing 18% and 7% of the total inhibitory current in NM and NL, respectively, at the end of the 50-pulse, 200-Hz stimulus. Finally, we show that the glycinergic component is functionally relevant, as its elimination reduced inhibition of discharges evoked by current injection into NM neurons. PMID:24198323

  5. Argon retentivity of hornblendes: A field experiment in a slowly cooled metamorphic terrane

    SciTech Connect

    Onstott, T.C.; Peacock, M.W. )

    1987-11-01

    Hornblende from samples of amphibolite and granitic gneiss, collected within a single outcrop in the central Adirondacks, yield significantly different {sup 40}Ar*/{sup 39}Ark{sub K} dates of 948 {plus minus} 5 and 907 {plus minus} 5 Ma. Assuming that this terrane cooled slowly following high-grade metamorphism and that the samples have experienced the same thermal history, the difference in dates apparently reflects a corresponding difference in blocking temperature for diffusion of radiogenic argon in these hornblende samples. The Fe/(Fe + Mg + Mn) of the hornblende samples are 0.8 and 0.6, the higher ratio corresponding to the younger {sup 40}Ar*/{sup 39}Ar{sub k} date. Transmission electron microscopy observations indicate that both hornblende samples are homogeneous and devoid of any exsolution, but contain zones of fibrous phyllosilicates {approximately} 0.1 to 2 {mu}m wide parallelling (100) and (110). These alteration zones probably formed during post-metamorphic cooling as a result of the migration of fluids through the hornblendes, and are obvious pathways for argon escape from hornblende. As these features are more abundant in the hornblende sample with the younger {sup 40}Ar/{sup 39}Ar date and higher Fe/(Fe + Mg + Mn), they may influence the argon blocking temperature by effectively partitioning the hornblende grains into diffusion domains of varying size. Biotite from the granitic gneiss yields an {sup 40}Ar*/{sup 39}Ar{sub k} date of 853 {plus minus} 2 Ma, with a mildly discordant step-heating spectrum that in part reflects the degassing of submicroscopic inclusions precipitated during alteration of the host biotite. Plagioclase from the amphibolite yields a {sup 40}Ar/{sup 39}Ar{sub k} integrated date of 734 {plus minus} 3 Ma.

  6. Argon retentivity of hornblendes: A field experiment in a slowly cooled metamorphic terrane

    NASA Astrophysics Data System (ADS)

    Onstott, T. C.; Peacock, M. W.

    1987-11-01

    Hornblende from samples of amphibolite and granitic gneiss, collected within a single outcrop in the central Adirondacks, yield significantly different 40Ar ∗/39Ar k dates of 948 ± 5 and 907 ± 5 Ma. Assuming that this terrane cooled slowly following high-grade metamorphism and that the samples have experienced the same thermal history, the difference in dates apparently reflects a corresponding difference in blocking temperature for diffusion of radiogenic argon in these hornblende samples. The Fe/(Fe + Mg + Mn) of the hornblende samples are 0.8 and 0.6, the higher ratio corresponding to the younger 40Ar ∗/39Ar k date. Transmission electron microscopy observations indicate that both hornblende samples are homogeneous and devoid of any exsolution, but contain zones of fibrous phyllosilicates ~0.1 to 2 μm wide parallelling (100) and (110). These alteration zones probably formed during post-metamorphic cooling as a result of the migration of fluids through the hornblendes, and are obvious pathways for argon escape from hornblende. As these features are more abundant in the hornblende sample with the younger 40Ar /39Ar date and higher Fe/(Fe + Mg + Mn), they may influence the argon blocking temperature by effectively partitioning the hornblende grains into diffusion domains of varying size. Biotite from the granitic gneiss yields an 40Ar ∗/39Ar k date of 853 ± 2 Ma, with a mildly discordant stepheating spectrum that in part reflects the degassing of submicroscopic inclusions precipitated during alteration of the host biotite. Plagioclase from the amphibolite yields a 40Ar ∗/39Ar k integrated date of 734 ± 3 Ma. All the 40Ar /39Ar data are consistent with postmetamorphic cooling rates of 1° to 5°C/Ma.

  7. The slowly pulsating B-star 18 Pegasi: A testbed for upper main sequence stellar evolution

    NASA Astrophysics Data System (ADS)

    Irrgang, A.; Desphande, A.; Moehler, S.; Mugrauer, M.; Janousch, D.

    2016-06-01

    The predicted width of the upper main sequence in stellar evolution models depends on the empirical calibration of the convective overshooting parameter. Despite decades of discussions, its precise value is still unknown and further observational constraints are required to gauge it. Based on a photometric and preliminary asteroseismic analysis, we show that the mid B-type giant 18 Peg is one of the most evolved members of the rare class of slowly pulsating B-stars and, thus, bears tremendous potential to derive a tight lower limit for the width of the upper main sequence. In addition, 18 Peg turns out to be part of a single-lined spectroscopic binary system with an eccentric orbit that is greater than 6 years. Further spectroscopic and photometric monitoring and a sophisticated asteroseismic investigation are required to exploit the full potential of this star as a benchmark object for stellar evolution theory. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programmes 265.C-5038(A), 069.C-0263(A), and 073.D-0024(A). Based on observations collected at the Centro Astronómico Hispano Alemán (CAHA) at Calar Alto, operated jointly by the Max-Planck Institut für Astronomie and the Instituto de Astrofísica de Andalucía (CSIC), proposals H2005-2.2-016 and H2015-3.5-008. Based on observations made with the William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias, proposal W15BN015. Based on observations obtained with telescopes of the University Observatory Jena, which is operated by the Astrophysical Institute of the Friedrich-Schiller-University.

  8. Simple expressions of the nuclear relaxation rate enhancement due to quadrupole nuclei in slowly tumbling molecules

    NASA Astrophysics Data System (ADS)

    Fries, Pascal H.; Belorizky, Elie

    2015-07-01

    For slowly tumbling entities or quasi-rigid lattices, we derive very simple analytical expressions of the quadrupole relaxation enhancement (QRE) of the longitudinal relaxation rate R1 of nuclear spins I due to their intramolecular magnetic dipolar coupling with quadrupole nuclei of arbitrary spins S ≥ 1. These expressions are obtained by using the adiabatic approximation for evaluating the time evolution operator of the quantum states of the quadrupole nuclei S. They are valid when the gyromagnetic ratio of the spin S is much smaller than that of the spin I. The theory predicts quadrupole resonant peaks in the dispersion curve of R1 vs magnetic field. The number, positions, relative intensities, Lorentzian shapes, and widths of these peaks are explained in terms of the following properties: the magnitude of the quadrupole Hamiltonian and the asymmetry parameter of the electric field gradient (EFG) acting on the spin S, the S-I inter-spin orientation with respect to the EFG principal axes, the rotational correlation time of the entity carrying the S-I pair, and/or the proper relaxation time of the spin S. The theory is first applied to protein amide protons undergoing dipolar coupling with fast-relaxing quadrupole 14N nuclei and mediating the QRE to the observed bulk water protons. The theoretical QRE agrees well with its experimental counterpart for various systems such as bovine pancreatic trypsin inhibitor and cartilages. The anomalous behaviour of the relaxation rate of protons in synthetic aluminium silicate imogolite nano-tubes due to the QRE of 27Al (S = 5/2) nuclei is also explained.

  9. Simple expressions of the nuclear relaxation rate enhancement due to quadrupole nuclei in slowly tumbling molecules

    SciTech Connect

    Fries, Pascal H.; Belorizky, Elie

    2015-07-28

    For slowly tumbling entities or quasi-rigid lattices, we derive very simple analytical expressions of the quadrupole relaxation enhancement (QRE) of the longitudinal relaxation rate R{sub 1} of nuclear spins I due to their intramolecular magnetic dipolar coupling with quadrupole nuclei of arbitrary spins S ≥ 1. These expressions are obtained by using the adiabatic approximation for evaluating the time evolution operator of the quantum states of the quadrupole nuclei S. They are valid when the gyromagnetic ratio of the spin S is much smaller than that of the spin I. The theory predicts quadrupole resonant peaks in the dispersion curve of R{sub 1} vs magnetic field. The number, positions, relative intensities, Lorentzian shapes, and widths of these peaks are explained in terms of the following properties: the magnitude of the quadrupole Hamiltonian and the asymmetry parameter of the electric field gradient (EFG) acting on the spin S, the S-I inter-spin orientation with respect to the EFG principal axes, the rotational correlation time of the entity carrying the S–I pair, and/or the proper relaxation time of the spin S. The theory is first applied to protein amide protons undergoing dipolar coupling with fast-relaxing quadrupole {sup 14}N nuclei and mediating the QRE to the observed bulk water protons. The theoretical QRE agrees well with its experimental counterpart for various systems such as bovine pancreatic trypsin inhibitor and cartilages. The anomalous behaviour of the relaxation rate of protons in synthetic aluminium silicate imogolite nano-tubes due to the QRE of {sup 27}Al (S = 5/2) nuclei is also explained.

  10. A comparative study of rapidly and slowly rotating dynamical regimes in a terrestrial general circulation model

    NASA Technical Reports Server (NTRS)

    Del Genio, Anthony D.; Suozzo, Robert J.

    1987-01-01

    As a preliminary step in the development of a general circulation model for general planetary use, a simplified vesion of thef GISS Model I GCM has been run at various rotation periods to investigate differences between the dynamical regimes of rapidly and slowly rotating planets. To isolate the dynamical processes, the hydrologic cycle is suppressed and the atmosphere is forced with perpetual annual mean solar heating. All other parameters except the rotation period remain fixed at their terrestrial values. Experiments were conducted for rotation periods of 2/3, 1, 2, 4, 8, 16, 64 and 256 days. The results are in qualitative agreement with similar experiments carried out previously with other GCMs and with certain aspects of one Venus GCM simulation. As rotation rate decreases, the energetics shifts from baroclinc to quasi-barotropic when the Rossby radius of deformation reaches planetary scale. The Hadley cell expands poleward and replaces eddies as the primary mode of large-scale heat transport. Associated with this is a poleward shift of the baroclinic zone and jet stream and a reduction of the equator-pole temperature contrast. Midlatitude jet strength peaks at 8 days period, as does the weak positive equatorial zonal wind which occurs at upper levels at all rotation periods. Eddy momentum transport switches from poleward to equatorward at the same period. Tropospheric mean static stability generally increases in the tropics and decreases in midlatitudes as rotation rate decreases, but the global mean static stability is independent of rotation rate. The peak in the eddy kinetic energy spectrum shifts toward lower wavenumbers, reaching wavenumber 1 at a period of 8 days. Implications of these results for the dynamics of Venus and Titan are discussed. Specifically, it is suggested that the extent of low-level convection determines whether the Gierasch mechanism contributes significantly to equatorial superrotation on these planets.

  11. Identification of vagal sensory receptors in the rat lung: are there subtypes of slowly adapting receptors?

    PubMed Central

    Bergren, D R; Peterson, D F

    1993-01-01

    1. We studied the characteristics of pulmonary sensory receptors whose afferent fibres are in the left vagus nerve of opened-chest rats. The activity of these receptors was recorded during mechanical ventilation approximating eupnoea, as well as during deflation, stepwise inflations and constant-pressure inflations of the lungs. Data were also collected from closed-chest rats and analysed separately. 2. Ninety-four per cent of receptors were located in the ipsilateral lung or airways with the remainder in the contralateral lung. 3. Not only were slowly adapting receptors (SARs) the most abundant pulmonary receptors but 21% of them were either exclusively or predominantly active during the deflationary phase of the ventilatory cycle. Deflationary units were found in opened- and closed-chest rats. The average conduction velocity for all fibres innervating SARs averaged 29.7 m s-1. 4. We found rapidly adapting receptors (RARs) to be extremely rare in the rat. Their activity was sparse and irregular. The conduction velocities of fibres innervating RARs averaged 12.3 m s-1. 5. Far more abundant than RARs in the remaining population of pulmonary fibres were C fibres. They were observed to have an average conduction velocity of 2.1 m s-1, base-level activity which was irregular and a high pressure threshold of activation and were stimulated by intravenous capsaicin injection. 6. Notable differences exist between pulmonary receptors in rats and those reported in other species. The variations include the abundant existence of intrapulmonary SARs with exclusively deflationary modulation and the rarity of RARs. We also encountered C fibres which have not previously been described systematically in the rat. PMID:8229824

  12. Response of Simulated Mixed-Phase Arctic Stratus Clouds to Slowly Activated Ice Nuclei

    NASA Astrophysics Data System (ADS)

    Fridlind, A. M.; Avramov, A.; Ackerman, A. S.; Alpert, P. A.; Knopf, D. A.

    2014-12-01

    Supercooled mixed-phase cloud decks are common in the Arctic, often persisting for days. Individual ice crystals in such clouds have relatively short lifetimes, typically an hour or less. Thus new ice crystals must be generated continuously in such long-lived cloud layers. Field campaigns investigating the microphysics of the simplest such clouds—unseeded single-layer cases in coupled or decoupled boundary layers—have aimed to measure the background ice nuclei (IN) required to initiate ice formation processes, specifically by measuring the concentration of IN above cloud top that are active at water saturation at cloud-top temperature. In previous detailed simulations of observed case studies, we demonstrated that if all ambient IN are assumed to be activated rapidly, and if there is no surface source of IN over pack ice or efficient multiplication process in the absence of riming, as commonly assumed, then overlying IN concentrations must exceed those of in-cloud ice crystals by a factor of order 10-100 or more, generally much higher than measured. However, under such conditions, entrainment and rapid activation quickly achieve a long-lived quasi-steady cloud microphysical state in simulations that seems consistent with that commonly observed. These previous studies made the assumption that all relevant IN have a lifetime of roughly one second at water saturation under cloud-top conditions, using a singular ice nucleation scheme. Here we investigate the behavior of the same cloud systems in the presence of IN with longer activation time scales, including those only available in the contact mode and those with a wider range of lifetimes under in-cloud conditions. We make a range of assumptions about IN properties to constrain ice nucleation schemes to the degree possible using field data. When ice crystals are primarily sustained by slowly activated IN, we find that the relative depletion rate of the boundary-layer reservoir of IN impacts the degree of quasi

  13. Testing the Completeness of the SDSS Colour Selection for Ultramassive, Slowly Spinning Black Holes

    NASA Astrophysics Data System (ADS)

    Bertemes, Caroline; Trakhtenbrot, Benny; Schawinski, Kevin; Done, Chris; Elvis, Martin

    2016-09-01

    We investigate the sensitivity of the colour-based quasar selection algorithm of the Sloan Digital Sky Survey to several key physical parameters of supermassive black holes (SMBHs), focusing on BH spin (a★) at the high BH-mass regime (MBH ≥ 109 M⊙). We use a large grid of model spectral energy distribution, assuming geometrically-thin, optically-thick accretion discs, and spanning a wide range of five physical parameters: BH mass MBH, BH spin a★, Eddington ratio L/LEdd, redshift z, and inclination angle inc. Based on the expected fluxes in the SDSS imaging ugriz bands, we find that ˜99.8% of our models with MBH ≤ 109.5 M⊙ are selected as quasar candidates and thus would have been targeted for spectroscopic follow-up. However, in the extremely high-mass regime, ≥1010M⊙, we identify a bias against slowly/retrograde spinning SMBHs. The fraction of SEDs that would have been selected as quasar candidates drops below ˜50% for a★ < 0 across 0.5 < z < 2. For particularly massive BHs, with MBH ≃ 3 × 1010 M⊙, this rate drops below ˜20%, and can be yet lower for specific redshifts. We further find that the chances of identifying any hypothetical sources with MBH = 1011 M⊙ by colour selection would be extremely low at the level of ˜3%. Our findings, along with several recent theoretical arguments and empirical findings, demonstrate that the current understanding of the SMBH population at the high-MBH, and particularly the low- or retrograde-spinning regime, is highly incomplete.

  14. Slowly fading super-luminous supernovae that are not pair-instability explosions

    NASA Astrophysics Data System (ADS)

    Nicholl, M.; Smartt, S. J.; Jerkstrand, A.; Inserra, C.; McCrum, M.; Kotak, R.; Fraser, M.; Wright, D.; Chen, T.-W.; Smith, K.; Young, D. R.; Sim, S. A.; Valenti, S.; Howell, D. A.; Bresolin, F.; Kudritzki, R. P.; Tonry, J. L.; Huber, M. E.; Rest, A.; Pastorello, A.; Tomasella, L.; Cappellaro, E.; Benetti, S.; Mattila, S.; Kankare, E.; Kangas, T.; Leloudas, G.; Sollerman, J.; Taddia, F.; Berger, E.; Chornock, R.; Narayan, G.; Stubbs, C. W.; Foley, R. J.; Lunnan, R.; Soderberg, A.; Sanders, N.; Milisavljevic, D.; Margutti, R.; Kirshner, R. P.; Elias-Rosa, N.; Morales-Garoffolo, A.; Taubenberger, S.; Botticella, M. T.; Gezari, S.; Urata, Y.; Rodney, S.; Riess, A. G.; Scolnic, D.; Wood-Vasey, W. M.; Burgett, W. S.; Chambers, K.; Flewelling, H. A.; Magnier, E. A.; Kaiser, N.; Metcalfe, N.; Morgan, J.; Price, P. A.; Sweeney, W.; Waters, C.

    2013-10-01

    Super-luminous supernovae that radiate more than 1044 ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of `pair-instability' supernovae. Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of 56Ni are synthesized; this isotope decays to 56Fe via 56Co, powering bright light curves. Such massive progenitors are expected to have formed from metal-poor gas in the early Universe. Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova. Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae, which are not powered by radioactivity. Modelling our observations with 10-16 solar masses of magnetar-energized ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 × 10-6 times that of the core-collapse rate.

  15. Struck by lightning or slowly suffocating – gendered trajectories into depression

    PubMed Central

    Danielsson, Ulla; Bengs, Carita; Lehti, Arja; Hammarström, Anne; Johansson, Eva E

    2009-01-01

    Background In family practice depression is a common mental health problem and one with marked gender differences; women are diagnosed as depressed twice as often as men. A more comprehensive explanatory model of depression that can give an understanding of, and tools for changing, this gender difference is called for. This study explores how primary care patients experience, understand and explain their depression. Methods Twenty men and women of varying ages and socioeconomic backgrounds diagnosed with depression according to ICD-10 were interviewed in-depth. Data were assessed and analyzed using Grounded Theory. Results The core category that emerged from analysis was "Gendered trajectories into depression". Thereto, four categories were identified – "Struck by lightning", "Nagging darkness", "Blackout" and "Slowly suffocating" – and presented as symbolic illness narratives that showed gendered patterns. Most of the men in our study considered that their bodies were suddenly "struck" by external circumstances beyond their control. The stories of study women were more diverse, reflecting all four illness narratives. However, the dominant pattern was that women thought that their depression emanated from internal factors, from their own personality or ways of handling life. The women were more preoccupied with shame and guilt, and conveyed a greater sense of personal responsibility and concern with relationships. Conclusion Recognizing gendered narratives of illness in clinical consultation may have a salutary potential, making more visible depression among men while relieving self-blame among women, and thereby encouraging the development of healthier practices of how to be a man or a woman. PMID:19671133

  16. Slowly contracting muscles power the rapid jumping of planthopper insects (Hemiptera, Issidae).

    PubMed

    Burrows, M; Meinertzhagen, I A; Bräunig, P

    2014-01-01

    The planthopper insect Issus produces one of the fastest and most powerful jumps of any insect. The jump is powered by large muscles that are found in its thorax and that, in other insects, contribute to both flying and walking movements. These muscles were therefore analysed by transmission electron microscopy to determine whether they have the properties of fast-acting muscle used in flying or those of more slowly acting muscle used in walking. The muscle fibres are arranged in a parallel bundle that inserts onto an umbrella-shaped tendon. The individual fibres have a diameter of about 70 μm and are subdivided into myofibrils a few micrometres in diameter. No variation in ultrastructure was observed in various fibres taken from different parts of the muscle. The sarcomeres are about 15 μm long and the A bands about 10 μm long. The Z lines are poorly aligned within a myofibril. Mitochondrial profiles are sparse and are close to the Z lines. Each thick filament is surrounded by 10-12 thin filaments and the registration of these arrays of filaments is irregular. Synaptic boutons from the two excitatory motor neurons to the muscle fibres are characterised by accumulations of ~60 translucent 40-nm-diameter vesicle profiles per section, corresponding to an estimated 220 vesicles, within a 0.5-μm hemisphere at a presynaptic density. All ultrastructural features conform to those of slow muscle and thus suggest that the muscle is capable of slow sustained contractions in keeping with its known actions during jumping. A fast and powerful movement is thus generated by a slow muscle. PMID:24135974

  17. Inelastic Character of Solitons of Slowly Varying gKdV Equations

    NASA Astrophysics Data System (ADS)

    Muñoz, Claudio

    2012-09-01

    In this paper we study soliton-like solutions of the variable coefficients, the subcritical gKdV equation u_t + (u_{xx} -λ u + a(\\varepsilon x) u^m )_x =0,quad in quad {R}_t×{R}_x, quad m=2,3 { and } 4, with {λ≥ 0, a(\\cdot ) in (1,2)} a strictly increasing, positive and asymptotically flat potential, and {\\varepsilon} small enough. In previous works (Muñoz in Anal PDE 4:573-638, 2011; On the soliton dynamics under slowly varying medium for generalized KdV equations: refraction vs. reflection, SIAM J. Math. Anal. 44(1):1-60, 2012) the existence of a pure, global in time, soliton u( t) of the above equation was proved, satisfying lim_{tto -infty}\\|u(t) - Q_1(\\cdot -(1-λ)t) \\|_{H^1({R})} =0,quad 0≤ λ<1, provided {\\varepsilon} is small enough. Here R( t, x) := Q c ( x - ( c - λ) t) is the soliton of R t + ( R xx - λ R + R m ) x = 0. In addition, there exists {tilde λ in (0,1)} such that, for all 0 < λ < 1 with {λneq tilde λ} , the solution u( t) satisfies sup_{t≫ 1/\\varepsilon}\\|u(t) - kappa(λ)Q_{c_infty}(\\cdot-ρ(t)) \\|_{H^1({R})}lesssim \\varepsilon^{1/2}. Here {{ρ'(t) ˜ (c_infty(λ) -λ)}} , with {{kappa(λ)=2^{-1/(m-1)}}} and {{c_infty(λ)>λ}} in the case {0<λrsim \\varepsilon^{1 +δ}, for any {{δ>0}} fixed. This bound clarifies the existence of a dispersive tail and the difference with the standard solitons of the constant coefficients, gKdV equation.

  18. KIC 10526294: a slowly rotating B star with rotationally split, quasi-equally spaced gravity modes

    NASA Astrophysics Data System (ADS)

    Pápics, P. I.; Moravveji, E.; Aerts, C.; Tkachenko, A.; Triana, S. A.; Bloemen, S.; Southworth, J.

    2014-10-01

    Context. Massive stars are important for the chemical enrichment of the universe. Since internal mixing processes influence their lives, it is very important to place constraints on the corresponding physical parameters, such as core overshooting and the internal rotation profile, so as to calibrate their stellar structure and evolution models. Although asteroseismology has been shown to be able to deliver the most precise constraints so far, the number of detailed seismic studies delivering quantitative results is limited. Aims: Our goal is to extend this limited sample with an in-depth case study and provide a well-constrained set of asteroseismic parameters, contributing to the ongoing mapping efforts of the instability strips of the β Cep and slowly pulsating B (SPB) stars. Methods: We derived fundamental parameters from high-resolution spectra using spectral synthesis techniques. We used custom masks to obtain optimal light curves from the original pixel level data from the Kepler satellite. We used standard time-series analysis tools to construct a set of significant pulsation modes that provide the basis for the seismic analysis carried out afterwards. Results: We find that KIC 10526294 is a cool SPB star, one of the slowest rotators ever found. Despite this, the length of Kepler observations is sufficient to resolve narrow rotationally split multiplets for each of its nineteen quasi-equally spaced dipole modes. The number of detected consecutive (in radial order) dipole modes in this series is higher than ever before. The observed amount of splitting shows an increasing trend towards longer periods, which - largely independent of the seismically calibrated stellar models - points towards a non-rigid internal rotation profile. From the average splitting we deduce a rotation period of ~188 days. From seismic modelling, we find that the star is young with a central hydrogen mass fraction Xc> 0.64; it has a core overshooting αov ≤ 0.15. Based on

  19. Earthquakes in western Iberia: improving the understanding of lithospheric deformation in a slowly deforming region

    NASA Astrophysics Data System (ADS)

    Custódio, S.; Dias, N. A.; Carrilho, F.; Góngora, E.; Rio, I.; Marreiros, C.; Morais, I.; Alves, P.; Matias, L.

    2015-10-01

    of western Iberia presented in this article opens important questions concerning the regional seismotectonics. This work shows that the study of low-magnitude earthquakes using dense seismic deployments is a powerful tool to study lithospheric deformation in slowly deforming regions, such as western Iberia, where high-magnitude earthquakes occur with long recurrence intervals.

  20. Jupiter's winds and Arnol'd's second stability theorem: Slowly moving waves and neutral stability

    NASA Technical Reports Server (NTRS)

    Stamp, Andrew P.; Dowling, Timothy E.

    1993-01-01

    Since the Voyager encounters in 1979, it has been known that Jupiter's cloud-top zonal winds violate the barotropic stability criterion. A vortex-tube stretching analysis of the Voyager wind data indicates that the more general Charney-Stern stability criterion is also violated. On the other hand, the zonal winds determined by tracking cloud features in Hubble Space Telescope images taken in 1991 precisely match the zonal winds determined by tracking cloud features in Voyager images, and it is hard to understand how a complicated zonal wind profile like Jupiter's could be unstable and yet not change at all in 12 years. In fact, there are at least two unknown ways to violate the Charney-Stern stability criterion and still have a stable flow. The better known of these is called Fjortoft's theorem, or Arnol'd's 1st theorem for the case of large-amplitude perturbations. Although the Fjortoft-Arnol'd theorem has been extended from the quasi-geostrophic equations to the primitive equations, the basic requirement that the potential vorticity be an increasing function of streamfunction is opposite to the case found in Jupiter, where the Voyager data indicate that the potential vorticity is a decreasing function of streamfunction. But this second case is precisely that which is covered by Arnol'd's 2nd stability theorem. In fact, the Voyager data suggest that Jupiter's zonal winds are neutrally stable with respect to Arnol'd's 2nd stability theorem. Here, we analyze the linear stability problem of a one-parameter family of sinusoidal zonal wind profiles that are close to neutral stability with respect to Arnol'd's 2nd stability theorem. We find numerically that the most unstable mode is always stationary, which may help to explain the slowly moving mode 10 waves observed on Jupiter. We find that violation of Arnol'd's 2nd stability theorem is both necessary and sufficient for instability of sinusoidal profiles. However, there appears to be no simple extension of Arnol'd's 2

  1. Isotopic disequilibrium and lower crustal contamination in slowly ascending magmas: Insights from Proterozoic anorthosites

    NASA Astrophysics Data System (ADS)

    Bybee, G. M.; Ashwal, L. D.

    2015-10-01

    disequilibrium geometries cannot be explained by melting of the lower crust. Assimilation of crust with distinctive Sr, Nd and Pb isotopic compositions does, however, explain the origin of decoupling in internal mineral isotopic compositions. We also find unexpected patterns of internal isotopic disequilibrium, such as isotopically radiogenic orthopyroxene relative to plagioclase and differences in plagioclase isotopic disequilibrium between orthopyroxene- and olivine-bearing samples. These various lines of evidence provide strong support for the generation of crustal isotopic signatures through assimilation, and not anatexis, of the lower crust. These isotopic data show that anorthosite petrogenesis likely involves significant differentiation and solidification at lower crustal depths, followed by ascent of high-crystallinity bodies (⩾50% crystallinity) to mid- or upper crustal levels. We show that protracted lower crustal differentiation imparts a clear chemical and isotopic signature on mantle-derived magmas of Proterozoic anorthosites and that this process is central in the development of such slowly ascending, plagioclase-rich magmas.

  2. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.

    2016-01-01

    Purpose of Review This article presents a practical and informative approach to the evaluation of a patient with a rapidly progressive dementia (RPD). Recent Findings Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. Aside from prion diseases, the most common causes of RPD are atypical presentations of other neurodegenerative disorders, curable disorders including autoimmune encephalopathies, as well as some infections, and neoplasms. Numerous recent case reports suggest dural arterial venous fistulas sometimes cause RPDs. Summary RPDs, in which patients typically develop dementia over weeks to months, require an alternative differential than the slowly progressive dementias that occur over a few years. Because of their rapid decline, patients with RPDs necessitate urgent evaluation and often require an extensive workup, typically with multiple tests being sent or performed concurrently. Jakob-Creutzfeldt disease, perhaps the prototypical RPD, is often the first diagnosis many neurologists consider when treating a patient with rapid cognitive decline. Many conditions other than prion disease, however, including numerous reversible or curable conditions, can present as an RPD. This chapter discusses some of the major etiologies for RPDs and offers an algorithm for diagnosis. PMID:27042906

  3. Early-branching or fast-evolving eukaryotes? An answer based on slowly evolving positions.

    PubMed

    Philippe, H; Lopez, P; Brinkmann, H; Budin, K; Germot, A; Laurent, J; Moreira, D; Müller, M; Le Guyader, H

    2000-06-22

    The current paradigm of eukaryotic evolution is based primarily on comparative analysis of ribosomal RNA sequences. It shows several early-emerging lineages, mostly amitochondriate, which might be living relics of a progressive assembly of the eukaryotic cell. However, the analysis of slow-evolving positions, carried out with the newly developed slow-fast method, reveals that these lineages are, in terms of nucleotide substitution, fast-evolving ones, misplaced at the base of the tree by a long branch attraction artefact. Since the fast-evolving groups are not always the same, depending on which macromolecule is used as a marker, this explains most of the observed incongruent phylogenies. The current paradigm of eukaryotic evolution thus has to be seriously re-examined as the eukaryotic phylogeny is presently best summarized by a multifurcation. This is consistent with the Big Bang hypothesis that all extant eukaryotic lineages are the result of multiple cladogeneses within a relatively brief period, although insufficiency of data is also a possible explanation for the lack of resolution. For further resolution, rare evolutionary events such as shared insertions and/or deletions or gene fusions might be helpful. PMID:10902687

  4. Phylogenetic clades of ovine progressive pneumonia virus (OPPV) associate with sheep TMEM154 genotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovine progressive pneumonia virus (OPPV) is a lentivirus within the Retroviridae family that infects sheep. OPPV-induced clinical disease progresses slowly over time and manifests primarily in the lungs and central nervous system. Symptoms include weight loss, respiratory distress, and inevitably ...

  5. [Recent advance in research of benign adult familial myoclonus epilepsy (BAFME): is BAFME a progressive disorder?].

    PubMed

    Hitomi, Takefumi; Takahashi, Ryosuke; Ikeda, Akio

    2014-01-01

    Benign adult familial myoclonus epilepsy (BAFME) is an adult onset, autosomal dominant disease characterized by cortical tremor and infrequent generalized seizures. BAFME was considered as non-progressive, but cortical tremor worsened in some of the aged patients. We investigated the disease progression of BAFME. Cortical tremor significantly worsened and amplitudes of giant somatosensory evoked potential significantly increased with age in BAFME. These findings suggest that a progressive increase of cortical hyperexcitability causes exaggeration of cortical tremor. The clinical anticipation, defined as earlier onset age of either cortical tremor or generalized seizures or new appearance of those symptoms in the next generation, was observed in all studied BAFME families. In addition, a higher degree of clinical anticipation was associated with maternal transmission than with paternal transmission. Despite a unknown causative gene for BAFME, our finding suggests that BAFME and diseases with unstable expanding repeats including those in non-coding regions, might share a similar molecular mechanism because such diseases often show clinical anticipation with maternal transmission. As mentioned above, at least some part of the symptoms and pathophysiology progress with aging or over generation in BAFME. PMID:25672731

  6. Use of HμREL Human Coculture System for Prediction of Intrinsic Clearance and Metabolite Formation for Slowly Metabolized Compounds.

    PubMed

    Hultman, Ia; Vedin, Charlotta; Abrahamsson, Anna; Winiwarter, Susanne; Darnell, Malin

    2016-08-01

    Design of slowly metabolized compounds is an important goal in many drug discovery projects. Standard hepatocyte suspension intrinsic clearance (CLint) methods can only provide reliable CLint values above 2.5 μL/min/million cells. A method that permits extended incubation time with maintained performance and metabolic activity of the in vitro system is warranted to allow in vivo clearance predictions and metabolite identification of slowly metabolized drugs. The aim of this study was to evaluate the static HμREL coculture of human hepatocytes with stromal cells to be set up in-house as a standard method for in vivo clearance prediction and metabolite identification of slowly metabolized drugs. Fourteen low CLint compounds were incubated for 3 days, and seven intermediate to high CLint compounds and a cocktail of cytochrome P450 (P450) marker substrates were incubated for 3 h. In vivo clearance was predicted for 20 compounds applying the regression line approach, and HμREL coculture predicted the human intrinsic clearance for 45% of the drugs within 2-fold and 70% of the drugs within 3-fold of the clinical values. CLint values as low as 0.3 μL/min/million hepatocytes were robustly produced, giving 8-fold improved sensitivity of robust low CLint determination, over the cutoff in hepatocyte suspension CLint methods. The CLint values of intermediate to high CLint compounds were at similar levels both in HμREL coculture and in freshly thawed hepatocytes. In the HμREL coculture formation rates for five P450-isoform marker reactions, paracetamol (CYP1A2), 1-OH-bupropion (CYP2B6), 4-OH-diclofenac (CYP2C9), and 1-OH-midazolam (3A4) were within the range of literature values for freshly thawed hepatocytes, whereas 1-OH-bufuralol (CYP2D6) formation rate was lower. Further, both phase I and phase II metabolites were detected and an increased number of metabolites were observed in the HμREL coculture compared to hepatocyte suspension. In conclusion, HμREL coculture can

  7. Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein.

    PubMed

    Chaurasiya, Kathy R; McCauley, Micah J; Wang, Wei; Qualley, Dominic F; Wu, Tiyun; Kitamura, Shingo; Geertsema, Hylkje; Chan, Denise S B; Hertz, Amber; Iwatani, Yasumasa; Levin, Judith G; Musier-Forsyth, Karin; Rouzina, Ioulia; Williams, Mark C

    2014-01-01

    The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalysed DNA elongation. Here, we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription. PMID:24345943

  8. Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein

    PubMed Central

    Chaurasiya, Kathy R.; McCauley, Micah J.; Wang, Wei; Qualley, Dominic F.; Wu, Tiyun; Kitamura, Shingo; Geertsema, Hylkje; Chan, Denise S.B.; Hertz, Amber; Iwatani, Yasumasa; Levin, Judith G.; Musier-Forsyth, Karin; Rouzina, Ioulia; Williams, Mark C.

    2014-01-01

    The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response and have broad activity against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalyzed DNA elongation. Here we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription. PMID:24345943

  9. Road-Aided Ground Slowly Moving Target 2D Motion Estimation for Single-Channel Synthetic Aperture Radar

    PubMed Central

    Wang, Zhirui; Xu, Jia; Huang, Zuzhen; Zhang, Xudong; Xia, Xiang-Gen; Long, Teng; Bao, Qian

    2016-01-01

    To detect and estimate ground slowly moving targets in airborne single-channel synthetic aperture radar (SAR), a road-aided ground moving target indication (GMTI) algorithm is proposed in this paper. First, the road area is extracted from a focused SAR image based on radar vision. Second, after stationary clutter suppression in the range-Doppler domain, a moving target is detected and located in the image domain via the watershed method. The target’s position on the road as well as its radial velocity can be determined according to the target’s offset distance and traffic rules. Furthermore, the target’s azimuth velocity is estimated based on the road slope obtained via polynomial fitting. Compared with the traditional algorithms, the proposed method can effectively cope with slowly moving targets partly submerged in a stationary clutter spectrum. In addition, the proposed method can be easily extended to a multi-channel system to further improve the performance of clutter suppression and motion estimation. Finally, the results of numerical experiments are provided to demonstrate the effectiveness of the proposed algorithm. PMID:26999140

  10. Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein

    NASA Astrophysics Data System (ADS)

    Chaurasiya, Kathy R.; McCauley, Micah J.; Wang, Wei; Qualley, Dominic F.; Wu, Tiyun; Kitamura, Shingo; Geertsema, Hylkje; Chan, Denise S. B.; Hertz, Amber; Iwatani, Yasumasa; Levin, Judith G.; Musier-Forsyth, Karin; Rouzina, Ioulia; Williams, Mark C.

    2014-01-01

    The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalysed DNA elongation. Here, we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription.

  11. Mycobacterium pseudoshottsii sp. nov., a slowly growing chromogenic species isolated from Chesapeake Bay striped bass (Morone saxatilis)

    USGS Publications Warehouse

    Rhodes, M.W.; Kator, H.; McNabb, A.; Deshayes, C.; Reyrat, J.-M.; Brown-Elliott, B. A.; Wallace, R., Jr.; Trott, K.A.; Parker, J.M.; Lifland, B.; Osterhout, G.; Kaattari, I.; Reece, K.; Vogelbein, W.; Ottinger, C.A.

    2005-01-01

    A group of slowly growing photochromogenic mycobacteria was isolated from Chesapeake Bay striped bass (Morone saxatilis) during an epizootic of mycobacteriosis. Growth characteristics, acid-fastness and 16S rRNA gene sequencing results were consistent with those of the genus Mycobacterium. Biochemical reactions, growth characteristics and mycolic acid profiles (HPLC) resembled those of Mycobacterium shottsii, a non-pigmented mycobacterium also isolated during the same epizootic. Sequencing of the 16S rRNA genes, the gene encoding the exported repeated protein (erp) and the gene encoding the 65 kDa heat-shock protein (hsp65) and restriction enzyme analysis of the hsp65 gene demonstrated that this group of isolates is unique. Insertion sequences associated with Mycobacterium ulcerans, IS2404 and IS2606, were detected by PCR. These isolates could be differentiated from other slowly growing pigmented mycobacteria by their inability to grow at 37 ??C, production of niacin and urease, absence of nitrate reductase, negative Tween 80 hydrolysis and resistance to isoniazid (1 ??g ml-1), p-nitrobenzoic acid, thiacetazone and thiophene-2-carboxylic hydrazide. On the basis of this polyphasic study, it is proposed that these isolates represent a novel species, Mycobacterium pseudoshottsii sp. nov. The type strain, L15T, has been deposited in the American Type Culture Collection as ATCC BAA-883T and the National Collection of Type Cultures (UK) as NCTC 13318T. ?? 2005 IUMS.

  12. Road-Aided Ground Slowly Moving Target 2D Motion Estimation for Single-Channel Synthetic Aperture Radar.

    PubMed

    Wang, Zhirui; Xu, Jia; Huang, Zuzhen; Zhang, Xudong; Xia, Xiang-Gen; Long, Teng; Bao, Qian

    2016-01-01

    To detect and estimate ground slowly moving targets in airborne single-channel synthetic aperture radar (SAR), a road-aided ground moving target indication (GMTI) algorithm is proposed in this paper. First, the road area is extracted from a focused SAR image based on radar vision. Second, after stationary clutter suppression in the range-Doppler domain, a moving target is detected and located in the image domain via the watershed method. The target's position on the road as well as its radial velocity can be determined according to the target's offset distance and traffic rules. Furthermore, the target's azimuth velocity is estimated based on the road slope obtained via polynomial fitting. Compared with the traditional algorithms, the proposed method can effectively cope with slowly moving targets partly submerged in a stationary clutter spectrum. In addition, the proposed method can be easily extended to a multi-channel system to further improve the performance of clutter suppression and motion estimation. Finally, the results of numerical experiments are provided to demonstrate the effectiveness of the proposed algorithm. PMID:26999140

  13. Contributions of unfrozen fraction and of salt concentration to the survival of slowly frozen human erythrocytes: influence of warming rate

    SciTech Connect

    Mazur, P.; Rigopoulos, N.

    1983-01-01

    The general belief is that slow freezing injury is either the result of exposure to high salt concentrations or the result of excessive cell shrinkage. Ordinarily, salt concentration and the amount of liquid in the unfrozen channels are reciprocally related; but they can be separated within limits by varying the total concentration of solutes in the suspending medium while holding the mass ratio of additive to salt constant, and by then slowly freezing samples to various subzero temperatures. The authors have recently reported that when human red cells are frozen under these conditions and thawed rapidly, survival is more dependent on the unfrozen water fraction than it is on the salt concentration in that fraction. The present work compares these results with those obtained with slow thawing. While the general conclusion remains unaltered, slowly thawed cells were able to survive the freezing of a higher fraction of extracellular water than were rapidly thawed cells. Calculations were made of the changes in cell volume during the equilibration with glycerol and the subsequent freezing involved in these experiments.

  14. Superior Mesenteric Artery Syndrome Complicated by Diabetic Ketoacidosis and Graves' Disease in Slowly Progressive Insulin Dependent Diabetes Mellitus (SPIDDM): A Case Report and a Review of the Literature.

    PubMed

    Hirai, Hiroyuki; Fukushima, Naotaro; Hasegawa, Koji; Watanabe, Tsuyoshi; Hasegawa, Osamu; Satoh, Hiroaki

    2016-01-01

    A 48-year-old woman with a history of diabetes was admitted for nausea and vomiting with body weight loss. A blood examination revealed high plasma glucose and thyroid hormone levels and metabolic acidosis. She was therefore diagnosed with both diabetic ketoacidosis (DKA) and hyperthyroidism. Nausea and vomiting continued intermittently despite the administration of saline and insulin. The patient was further diagnosed with superior mesenteric artery syndrome (SMAS) after abdominal computed tomography revealed that a horizontal portion of the duodenum was sandwiched between the aorta and the superior mesenteric artery. Clinicians should be vigilant for SMAS in patients with both DKA and hyperthyroidism who present body weight loss. PMID:27477411

  15. Transformation and utilization of slowly biodegradable organic matters in biological sewage treatment of anaerobic anoxic oxic systems.

    PubMed

    Zhang, Q H; Jin, P K; Ngo, H H; Shi, X; Guo, W S; Yang, S J; Wang, X C; Wang, X; Dzakpasu, M; Yang, W N; Yang, L

    2016-10-01

    This study examined the distribution of carbon sources in two anaerobic anoxic oxic (AAO) sewage treatment plants in Xi'an and investigated the transformation characteristics and utilization potential of slowly biodegradable organic matters (SBOM). Results indicated under anaerobic and aerobic conditions, SBOM could be transformed at a rate of 65% in 8h into more readily biologically utilizable substrates such as volatile fatty acids (VFAs), polysaccharides and proteins. Additionally, non-biodegradable humus-type substances which are difficult to biodegrade and readily accumulate, were also generated. These products could be further hydrolyzed to aldehyde and ketone compounds and then transformed into substances with significant oxygen-containing functional groups and utilized subsequently. The molecular weights of proteinoid substances had a wide distribution and tended to decrease over time. Long hours of microbial reaction increased the proportion of micromolecular substances. This particular increase generated significant bioavailability, which can greatly improve the efficiency of nitrogen removal. PMID:27347798

  16. Isolation and characterization of a unique group of slowly growing mycobacteria: description of Mycobacterium lentiflavum sp. nov.

    PubMed Central

    Springer, B; Wu, W K; Bodmer, T; Haase, G; Pfyffer, G E; Kroppenstedt, R M; Schröder, K H; Emler, S; Kilburn, J O; Kirschner, P; Telenti, A; Coyle, M B; Böttger, E C

    1996-01-01

    A distinct group of slowly growing mycobacteria was identified on the basis of growth characteristics, biochemical and lipid profiles, and nucleic acid analyses. The isolates showed growth at 22 to 37 degrees C, yellow pigmentation, and negative tests for Tween 80 hydrolysis, nicotinic acid, nitrate reductase, and urease; tests for arylsulfatase, pyrazinamidase, and heat-stable catalase were variable. Analysis of cellular fatty acids by gas-liquid chromatography and mycolic acids by thin-layer chromatography and high-performance liquid chromatography indicated a distinctive pattern which was unlike those of other species. Determination of the 16S rRNA gene sequence showed a unique sequence closely related to Mycobacterium simiae and M. genavense. On the basis of DNA homology studies, we suggest that these organisms are representatives of a novel species, for which the name M. lentiflavum sp. nov. is proposed. PMID:8727884

  17. A slowly rotating hollow sphere in a magnetic field: First steps to de-spin a space object

    NASA Astrophysics Data System (ADS)

    Youngquist, Robert C.; Nurge, Mark A.; Starr, Stanley O.; Leve, Frederick A.; Peck, Mason

    2016-03-01

    Modeling the interaction of a slowly rotating hollow conducting sphere in a magnetic field provided an understanding of the dynamics of orbiting space objects moving through the Earth's magnetic field. This analysis, performed in the late 1950s and limited to uniform magnetic fields, was innovative and acknowledged the pioneers who first observed rotary magnetism, in particular, the seminal work of Hertz in 1880. Now, there is interest in using a magnetic field produced by one space object to stop the spin of a second object so that docking can occur. In this paper, we consider, yet again, the interaction of a rotating hollow sphere in a magnetic field. We show that the predicted results can be tested experimentally, making this an interesting advanced student project. This analysis also sheds light on a rich set of previously unaddressed behaviors involving eddy currents.

  18. Effective control of Listeria monocytogenes by combination of nisin formulated and slowly released into a broth system.

    PubMed

    Chi-Zhang, Yundong; Yam, Kit L; Chikindas, Michael L

    2004-01-01

    In order to identify conditions for efficient food preservation by nisin, the sensitivity of Listeria monocytogenes to this preservative was studied under the following three model conditions: (1) the instantaneous addition of nisin into broth medium to simulate the formation of nisin in foods, (2) the slow delivery of nisin solution into broth medium using a pump to simulate the slow release of nisin from packaging materials to foods, (3) a combination of the two delivery methods. Based on the following results, we conclude that the antimicrobial effectiveness of nisin strongly depends on its mode of delivery. The instantaneous and slow methods for adding nisin inhibited L. monocytogenes, but over time of exposure, L. monocytogenes developed tolerance to nisin. Our data indicate that cells treated with instantaneously added nisin developed resistance to higher concentrations of nisin (200 IU/ml), compared to cells treated with slowly added nisin at the same total amount of the antimicrobial. Further studies indicated that nisin-tolerant cells recovered from treatments in which 200 IU/ml nisin was added instantaneously were likely to be mutants, which became resistant to the bacteriocin. In contrast, when 200 IU/ml of the antimicrobial was added slowly to the cells, only a temporary tolerance was developed; these cells became nisin-sensitive after passage through nisin-free medium. Due to the development of nisin-resistant cells, excessive amounts of nisin in the model system did not further inhibit L. monocytogenes. These results signify that excess nisin in foods does not necessarily improve the efficiency of controlling L. monocytogenes. Our data suggest that the combination of packaging material containing nisin used in conjunction with nisin-containing foods will provide the most effective means of preventing L. monocytogenes growth. PMID:14672827

  19. Bioavailability of slowly cycling soil phosphorus: major restructuring of soil P fractions over four decades in an aggrading forest.

    PubMed

    Richter, Daniel D; Allen, H Lee; Li, Jianwei; Markewitz, Daniel; Raikes, Jane

    2006-11-01

    Although low solubility and slow cycling control P circulation in a wide range of ecosystems, most studies that evaluate bioavailability of soil P use only indices of short-term supply. The objective here is to quantify changes in P fractions in an Ultisol during the growth of an old-field pine forest from 1957 to 2005, specifically changes with organic P (Po) and with inorganic P (Pi) associated with Fe and Al oxides as well as Ca compounds. Changes in soil P were estimated from archived mineral soil samples collected in 1962 shortly after pine seedlings were planted, and on six subsequent occasions (1968, 1977, 1982, 1990, 1997, and 2005) from eight permanent plots and four mineral soil layers (0-7.5, 7.5-15, 15-35, and 35-60 cm). Despite the net transfer of 82.5 kg ha(-1) of P from mineral soil into tree biomass and O horizons, labile soil P was not diminished, as indexed by anion exchange resins, and NaHCO(3) and Mehlich III extractants. An absence of depletion in most labile P fractions masks major restructuring of soil P chemistry driven by ecosystem development. During 28 years of forest growth, decreases were significant and substantial in slowly cycling Po and Pi associated with Fe and Al oxides and Ca compounds, and these accounted for most of the P supplied to biomass and O horizons, and for buffering labile soil fractions as well. Changes in soil P are attributed to the P sink strength of the aggrading forest (at 2.9 kg ha(-1) year(-1) over 28 years); legacies of fertilization, which enriched slowly cycling fractions of Po and Pi; and the changing biogeochemistry of the soil itself. PMID:16896767

  20. Slowly digestible waxy maize starch prepared by octenyl succinic anhydride esterification and heat-moisture treatment: glycemic response and mechanism.

    PubMed

    He, Jinhua; Liu, Jie; Zhang, Genyi

    2008-01-01

    The mechanism and molecular structure of the slowly digestible waxy maize starch prepared by octenyl succinic anhydride (OSA) esterification and heat-moisture treatment were investigated. The in vitro Englyst test showed a proportion of 28.3% slowly digestible starch (SDS) when waxy maize starch was esterified with 3% OSA (starch weight based, and it is named OSA-starch), and a highest SDS content of 42.8% was obtained after OSA-starch (10% moisture) was further heated at 120 degrees C for 4 h (named HOSA-starch). The in vivo glycemic response of HOSA-starch, which showed a delayed appearance of blood glucose peak and a significant reduction (32.2%) of the peak glucose concentration, further confirmed its slow digestion property. Amylopectin debranching analysis revealed HOSA-starch had the highest resistance to debranching enzymes of isoamylase and pullulanase, and a simultaneous decrease of K m and V m (enzyme kinetics) was also shown when HOSA-starch was digested by either alpha-amylase or amyloglucosidase, indicating that the slow digestion of HOSA-starch resulted from an uncompetitive inhibition of enzyme activity during digestion. Size exclusion chromatography analysis of HOSA-starch showed fragmented amylopectin molecules with more nonreducing ends that are favorable for RS conversion to SDS by the action of amyloglucosidase in the Englyst test. Further solubility analysis indicates that the water-insolubility of HOSA-starch is caused by OSA-mediated cross-linking of amylopectin and the hydrophobic interaction between OSA-modified starch molecules. The water-insolubility of HOSA-starch would decrease its enzyme accessibility, and the digestion products with attached OSA molecules might also directly act as the uncompetitive inhibitor to reduce the enzyme activity leading to a slow digestion of HOSA-starch. PMID:18067261

  1. Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system.

    PubMed Central

    Brown, B A; Wallace, R J; Onyi, G O

    1992-01-01

    MICs of clarithromycin against 324 clinical isolates belonging to eight species of slowly growing nontuberculous mycobacteria were determined by using a broth microdilution system. Isolates were inoculated into twofold drug dilutions in Middlebrook 7H9 broth (pH corrected to 7.4) and then incubated at 30 degrees C for 7 days for Mycobacterium marinum and for 14 days for all other species. The MIC for 90% of the strains (MIC90) was less than or equal to 0.5 micrograms/ml for isolates of Mycobacterium gordonae (6 strains), Mycobacterium scrofulaceum (5 strains), Mycobacterium szulgai (6 strains), and Mycobacterium kansasii (35 strains). MICs for M. marinum (25 strains) and Mycobacterium avium complex (237 strains) were higher, but 100% and 89% of the strains, respectively, were susceptible to less than or equal to 4 micrograms/ml. In contrast, MICs for five of six M. simiae strains were greater than 8 micrograms/ml, and the range of MICs for Mycobacterium nonchromogenicum varied from less than or equal to 0.125 to 8 micrograms/ml. For the 237 isolates of M. avium complex, the MIC50 was 2 micrograms/ml and the MIC90 was 8 micrograms/ml. MICs for most isolates (77%) were in the 1- to 4-micrograms/ml range. For the 80 isolates in this group known to be from AIDS patients, the MIC50 was 4 micrograms/ml and the MIC90 was 8 micrograms/ml. These MIC studies combined with preliminary clinical trials suggest that clarithromycin may be useful for drug therapy of most species of the slowly growing nontuberculous mycobacteria except M. simiae. PMID:1416891

  2. Slowly but surely.

    PubMed

    1997-06-01

    Oxfam UK/I in Chad has been building the capacity of women's income-generating activities through a strategy of long-term small-scale support over a period of many years to the Said Al Awine program. In the new Chad strategic four-year plan, gender is central to the development of a new phase of increasing the capacity of such organizations to network, lobby, and conduct policy research. The key to Oxfam's success in Chad has been long-term commitment and close work with poor, illiterate women. Oxfam UK/I began targeting urban women in 1988 in the informal sector of N'djamena to increase food security and improve living standards by encouraging small groups of women traders of basic foodstuffs to establish savings plans. Each group and each member held their own savings with the women investing 33%, Oxfam giving 33% as a subsidy, and Oxfam providing another 33% as a loan to be repaid. Many groups took out and repaid loans. The 16 groups in N'djamena came together in 1995 to form a union, with a representative from each group co-managing the joint fund for the union. More than 100 applications have been received to join the scheme. PMID:12320969

  3. Slowly balding black holes

    SciTech Connect

    Lyutikov, Maxim; McKinney, Jonathan C.

    2011-10-15

    The 'no-hair' theorem, a key result in general relativity, states that an isolated black hole is defined by only three parameters: mass, angular momentum, and electric charge; this asymptotic state is reached on a light-crossing time scale. We find that the no-hair theorem is not formally applicable for black holes formed from the collapse of a rotating neutron star. Rotating neutron stars can self-produce particles via vacuum breakdown forming a highly conducting plasma magnetosphere such that magnetic field lines are effectively ''frozen in'' the star both before and during collapse. In the limit of no resistivity, this introduces a topological constraint which prohibits the magnetic field from sliding off the newly-formed event horizon. As a result, during collapse of a neutron star into a black hole, the latter conserves the number of magnetic flux tubes N{sub B}=e{Phi}{sub {infinity}}/({pi}c({h_bar}/2{pi})), where {Phi}{sub {infinity}}{approx_equal}2{pi}{sup 2}B{sub NS}R{sub NS}{sup 3}/(P{sub NS}c) is the initial magnetic flux through the hemispheres of the progenitor and out to infinity. We test this theoretical result via 3-dimensional general relativistic plasma simulations of rotating black holes that start with a neutron star dipole magnetic field with no currents initially present outside the event horizon. The black hole's magnetosphere subsequently relaxes to the split-monopole magnetic field geometry with self-generated currents outside the event horizon. The dissipation of the resulting equatorial current sheet leads to a slow loss of the anchored flux tubes, a process that balds the black hole on long resistive time scales rather than the short light-crossing time scales expected from the vacuum no-hair theorem.

  4. Slowly balding black holes

    NASA Astrophysics Data System (ADS)

    Lyutikov, Maxim; McKinney, Jonathan C.

    2011-10-01

    The “no-hair” theorem, a key result in general relativity, states that an isolated black hole is defined by only three parameters: mass, angular momentum, and electric charge; this asymptotic state is reached on a light-crossing time scale. We find that the no-hair theorem is not formally applicable for black holes formed from the collapse of a rotating neutron star. Rotating neutron stars can self-produce particles via vacuum breakdown forming a highly conducting plasma magnetosphere such that magnetic field lines are effectively “frozen in” the star both before and during collapse. In the limit of no resistivity, this introduces a topological constraint which prohibits the magnetic field from sliding off the newly-formed event horizon. As a result, during collapse of a neutron star into a black hole, the latter conserves the number of magnetic flux tubes NB=eΦ∞/(πcℏ), where Φ∞≈2π2BNSRNS3/(PNSc) is the initial magnetic flux through the hemispheres of the progenitor and out to infinity. We test this theoretical result via 3-dimensional general relativistic plasma simulations of rotating black holes that start with a neutron star dipole magnetic field with no currents initially present outside the event horizon. The black hole’s magnetosphere subsequently relaxes to the split-monopole magnetic field geometry with self-generated currents outside the event horizon. The dissipation of the resulting equatorial current sheet leads to a slow loss of the anchored flux tubes, a process that balds the black hole on long resistive time scales rather than the short light-crossing time scales expected from the vacuum no-hair theorem.

  5. Congenital Hereditary Endothelial Dystrophy Caused by SLC4A11 Mutations Progresses to Harboyan Syndrome

    PubMed Central

    Siddiqui, Salina; Zenteno, Juan Carlos; Rice, Aine; Chacón-Camacho, Oscar; Naylor, Steven G.; Rivera-de la Parra, David; Spokes, David M.; James, Nigel; Toomes, Carmel; Inglehearn, Chris F.

    2013-01-01

    Purpose: Homozygous mutations in SLC4A11 cause 2 rare recessive conditions: congenital hereditary endothelial dystrophy (CHED), affecting the cornea alone, and Harboyan syndrome consisting of corneal dystrophy and sensorineural hearing loss. In addition, adult-onset Fuchs endothelial corneal dystrophy (FECD) is associated with dominant mutations in SLC4A11. In this report, we investigate whether patients with CHED go on to develop hearing loss and whether their parents, who are carriers of an SLC4A11 mutation, show signs of having FECD. Methods: Patients with CHED were screened for mutations in the SLC4A11 gene and underwent audiometric testing. The patients and their parents underwent a clinical examination and specular microscopy. Results: Molecular analyses confirmed SLC4A11 mutations in 4 affected individuals from 3 families. All the patients were found to have varying degrees of sensorineural hearing loss at a higher frequency range. Guttate lesions were seen in 2 of the 4 parents who were available for examination. Conclusions: Our observations suggest that CHED caused by homozygous SLC4A11 mutations progresses to Harboyan syndrome, but the severity of this may vary considerably. Patients with CHED should therefore be monitored for progressive hearing loss. We could not determine conclusively whether the parents of the patients with CHED were at increased risk of developing late-onset FECD. PMID:24351571

  6. Active translocon complexes labeled with GFP-Dad1 diffuse slowly as large polysome arrays in the endoplasmic reticulum.

    PubMed

    Nikonov, Andrei V; Snapp, Erik; Lippincott-Schwartz, Jennifer; Kreibich, Gert

    2002-08-01

    In the ER, the translocon complex (TC) functions in the translocation and cotranslational modification of proteins made on membrane-bound ribosomes. The oligosaccharyltransferase (OST) complex is associated with the TC, and performs the cotranslational N-glycosylation of nascent polypeptide chains. Here we use a GFP-tagged subunit of the OST complex (GFP-Dad1) that rescues the temperature-sensitive (ts) phenotype of tsBN7 cells, where Dad1 is degraded and N-glycosylation is inhibited, to study the lateral mobility of the TC by FRAP. GFP-Dad1 that is functionally incorporated into TCs diffuses extremely slow, exhibiting an effective diffusion constant (Deff) about seven times lower than that of GFP-tagged ER membrane proteins unhindered in their lateral mobility. Termination of protein synthesis significantly increases the lateral mobility of GFP-Dad1 in the ER membranes, but to a level that is still lower than that of free GFP-Dad1. This suggests that GFP-Dad1 as part of the OST remains associated with inactive TCs. Our findings that TCs assembled into membrane-bound polysomes diffuse slowly within the ER have mechanistic implications for the segregation of the ER into smooth and rough domains. PMID:12163472

  7. Toward a novel membrane process for organic carbon removal-fate of slowly biodegradable substrate in super fast membrane bioreactor.

    PubMed

    Sözen, S; Teksoy Başaran, S; Akarsubaşı, A; Ergal, I; Insel, G; Karaca, C; Orhon, D

    2016-08-01

    The study tested the performance of super fast membrane bioreactor (SFMBR) using starch as a slowly biodegradable substrate, exploring the fate of starch, and the response of the microbial community. SFMBR was operated at extremely low sludge ages of 0.5-2.0 days, with a hydraulic retention time of 1.0 h. Average values for permeate chemical oxygen demand (COD) always remained in the narrow range between 14 and 18 mg/L, regardless of the selected mode of MBR operation at different sludge ages. Soluble COD levels in the reactor were consistently higher than the corresponding permeate COD. Parameters defining process kinetics, determined by model calibration of oxygen uptake rate (OUR) profiles, varied as a function of sludge age. Model simulation of SFMBR performance indicated total removal of hydrolysis products so that permeate COD consisted of residual microbial products. PCR-DGGE experiments revealed significant shifts in the composition of the microbial community imposed by variations in the sludge age, reflecting on corresponding process kinetics. PMID:27154840

  8. Mimicking the End Organ Architecture of Slowly Adapting Type I Afferents May Increase the Durability of Artificial Touch Sensors

    PubMed Central

    Lesniak, Daine R.; Gerling, Gregory J.

    2015-01-01

    In effort to mimic the sensitivity and efficient information transfer of natural tactile afferents, recent work has combined force transducers and computational models of mechanosensitive afferents. Sensor durability, another feature important to sensor design, might similarly capitalize upon biological rules. In particular, gains in sensor durability might leverage insight from the compound end organ of the slowly adapting type I afferent, especially its multiple sites of spike initiation that reset each other. This work develops models of compound spiking sensors using a computational network of transduction functions and leaky integrate and fire models (together a spike encoder, the software element of a compound spiking sensor), informed by the output of an existing force transducer (hardware sensing elements of a compound spiking sensor). Individual force transducer failures are simulated with and without resetting between spike encoders to test the importance of both resetting and configuration on system durability. The results indicate that the resetting of adjacent spike encoders, upon the firing of a spike by any one, is an essential mechanism to maintain a stable overall response in the midst of transducer failure. Furthermore, results suggest that when resetting is enabled, the durability of a compound sensor is maximized when individual transducers are paired with spike encoders and multiple, paired units are employed. To explore these ideas more fully, use cases examine the design of a compound sensor to either reach a target lifetime with a set probability or determine how often to schedule maintenance to control the probability of failure. PMID:25705703

  9. Generation mechanism of the slowly drifting narrowband structure in the type IV solar radio bursts observed by AMATERAS

    SciTech Connect

    Katoh, Y.; Nishimura, Y.; Kumamoto, A.; Ono, T.; Iwai, K.; Misawa, H.; Tsuchiya, F.

    2014-05-20

    We investigate the type IV burst event observed by AMATERAS on 2011 June 7, and reveal that the main component of the burst was emitted from the plasmoid eruption identified in the EUV images of the Solar Dynamics Observatory (SDO)/AIA. We show that a slowly drifting narrowband structure (SDNS) appeared in the burst's spectra. Using statistical analysis, we reveal that the SDNS appeared for a duration of tens to hundreds of milliseconds and had a typical bandwidth of 3 MHz. To explain the mechanism generating the SDNS, we propose wave-wave coupling between Langmuir waves and whistler-mode chorus emissions generated in a post-flare loop, which were inferred from the similarities in the plasma environments of a post-flare loop and the equatorial region of Earth's inner magnetosphere. We assume that a chorus element with a rising tone is generated at the top of a post-flare loop. Using the magnetic field and plasma density models, we quantitatively estimate the expected duration of radio emissions generated from coupling between Langmuir waves and chorus emissions during their propagation in the post-flare loop, and we find that the observed duration and bandwidth properties of the SDNS are consistently explained by the proposed generation mechanism. While observations in the terrestrial magnetosphere show that the chorus emissions are a group of large-amplitude wave elements generated naturally and intermittently, the mechanism proposed in the present study can explain both the intermittency and the frequency drift in the observed spectra.

  10. The world's largest parafoil slowly deflates after carrying the X-38, V-131R, to a safe landing

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Looking like a giant air mattress, the world's largest parafoil slowly deflates seconds after it carried the latest version of the X-38, V-131R, to a landing on Rogers Dry Lake adjacent to NASA's Dryden Flight Research Center at Edwards, California, at the end of its first free flight, November 2, 2000. The X-38 prototypes are intended to perfect technology for a planned Crew Return Vehicle (CRV) 'lifeboat' to carry a crew to safety in the event of an emergency on the International Space Station. Free-flight tests of X-38 V-131R are evaluating upgraded avionics and control systems and the aerodynamics of the modified upper body, which is more representative of the final design of the CRV than the two earlier X-38 test craft, including a simulated hatch atop the body. The huge 7,500 square-foot parafoil will enable the CRV to land in the length of a football field after returning from space. The first three X-38's are air-launched from NASA's venerable NB-52B mother ship, while the last version, V-201, will be carried into space by a Space Shuttle and make a fully autonomous re-entry and landing.

  11. Structural characteristics of slowly digestible starch and resistant starch isolated from heat-moisture treated waxy potato starch.

    PubMed

    Lee, Chang Joo; Moon, Tae Wha

    2015-07-10

    The objective of this study was to investigate the structural characteristics of slowly digestible starch (SDS) and resistant starch (RS) fractions isolated from heat-moisture treated waxy potato starch. The waxy potato starch with 25.7% moisture content was heated at 120°C for 5.3h. Scanning electron micrographs of the cross sections of RS and SDS+RS fractions revealed a growth ring structure. The branch chain-length distribution of debranched amylopectin from the RS fraction had a higher proportion of long chains (DP ≥ 37) than the SDS+RS fraction. The X-ray diffraction intensities of RS and SDS+RS fractions were increased compared to the control. The SDS+RS fraction showed a lower gelatinization enthalpy than the control while the RS fraction had a higher value than the SDS+RS fraction. In this study we showed the RS fraction is composed mainly of crystalline structure and the SDS fraction consists of weak crystallites and amorphous regions. PMID:25857975

  12. Experimental Study of Homogeneous Isotropic Slowly-Decaying Turbulence in Giant Grid-Wind Tunnel Set Up

    NASA Astrophysics Data System (ADS)

    Aliseda, Alberto; Bourgoin, Mickael; Eswirp Collaboration

    2014-11-01

    We present preliminary results from a recent grid turbulence experiment conducted at the ONERA wind tunnel in Modane, France. The ESWIRP Collaboration was conceived to probe the smallest scales of a canonical turbulent flow with very high Reynolds numbers. To achieve this, the largest scales of the turbulence need to be extremely big so that, even with the large separation of scales, the smallest scales would be well above the spatial and temporal resolution of the instruments. The ONERA wind tunnel in Modane (8 m -diameter test section) was chosen as a limit of the biggest large scales achievable in a laboratory setting. A giant inflatable grid (M = 0.8 m) was conceived to induce slowly-decaying homogeneous isotropic turbulence in a large region of the test section, with minimal structural risk. An international team or researchers collected hot wire anemometry, ultrasound anemometry, resonant cantilever anemometry, fast pitot tube anemometry, cold wire thermometry and high-speed particle tracking data of this canonical turbulent flow. While analysis of this large database, which will become publicly available over the next 2 years, has only started, the Taylor-scale Reynolds number is estimated to be between 400 and 800, with Kolmogorov scales as large as a few mm . The ESWIRP Collaboration is formed by an international team of scientists to investigate experimentally the smallest scales of turbulence. It was funded by the European Union to take advantage of the largest wind tunnel in Europe for fundamental research.

  13. Ion Density and Temperature Measured by CINDI from the C/NOFS Spacecraft During a Slowly Rising Solar Cycle

    NASA Astrophysics Data System (ADS)

    Coley, W. R.; Heelis, R. A.

    2011-12-01

    The Ion Velocity Meter (IVM), a part of the CINDI instrument package on the C/NOFS spacecraft, has made over three years of in-situ measurements of plasma temperature, composition, density, and velocity in the 400-850 km altitude range of the equatorial ionosphere. The C/NOFS launch in April 2008 coincided with a period of unusually low solar activity with F10.7 cm radio fluxes consistently around 70 sfu. This resulted in a cold (~600 K in the pre-dawn region) low-density ionosphere near the spacecraft's 400 km perigee altitude and an unusually low O+/H+ transition height varying from 450 km at night to over 700 km during the day. Toward the end of 2009 solar activity began to slowly increase with F10.7 occasionally reaching 150 sfu. The variations of ion density, ion temperature, and the transition height are presented as a function of solar activity as well as their dependence on magnetic and geographic latitude, longitude, and altitude. Preliminary results indicate a relatively prompt response of ion density to F10.7 variations with a time scale of 1-3 days.

  14. MRI/MRS as a surrogate marker for clinical progression in GM1 gangliosidosis.

    PubMed

    Regier, Debra S; Kwon, Hyuk Joon; Johnston, Jean; Golas, Gretchen; Yang, Sandra; Wiggs, Edythe; Latour, Yvonne; Thomas, Sarah; Portner, Cindy; Adams, David; Vezina, Gilbert; Baker, Eva H; Tifft, Cynthia J

    2016-03-01

    Background GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in GLB1, encoding β-galactosidase. The range of severity is from type I infantile disease, lethal in early childhood, to type III adult onset, resulting in gradually progressive neurological symtpoms in adulthood. The intermediate group of patients has been recently classified as having type II late infantile subtype with onset of symptoms at one to three years of age or type II juvenile subtype with symptom onset at 2-10 years. To characterize disease severity and progression, six Late infantile and nine juvenile patients were evaluated using magnetic resonance imaging (MRI), and MR spectroscopy (MRS). Since difficulties with ambulation (gross motor function) and speech (expressive language) are often the first reported symptoms in type II GM1, patients were also scored in these domains. Deterioration of expressive language and ambulation was more rapid in the late infantile patients. Fourteen MRI scans in six Late infantile patients identified progressive atrophy in the cerebrum and cerebellum. Twenty-six MRI scans in nine juvenile patients revealed greater variability in extent and progression of atrophy. Quantitative MRS demonstrated a deficit of N-acetylaspartate in both the late infantile and juvenile patients with greater in the late infantile patients. This correlates with clinical measures of ambulation and expressive language. The two subtypes of type II GM1 gangliosidosis have different clinical trajectories. MRI scoring, quantitative MRS and brain volume correlate with clinical disease progression and may serve as important minimally-invasive outcome measures for clinical trials. © 2015 Wiley Periodicals, Inc. PMID:26646981

  15. Modeling of plasma processes in the slowly diverging magnetic fields at the exit of an applied-field magnetoplasmadynamic thruster

    SciTech Connect

    Li, Min; Tang, Hai-Bin; Ren, Jun-Xue; York, Thomas M.

    2013-10-15

    The performance of plasma thrusters with applied electric and magnetic fields can be enhanced by increasing the magnetic field strength, which is applied in the thrust chamber and the exit region propulsive plume. The ejected plasma which passes through a slowly diverging magnetic field will expand but can be restricted within the magnetic nozzle fields. To examine in detail the processes that occur, a new method with Particle-in-cell calculations is applied here. A two-dimensional axisymmetric particle dynamic code is used to model an AF-MPDT (Applied-field Magnetoplasmadynamic Thruster) for which extensive experimental data are available; it used Ar propellant and had applied magnetic coils of 101.5 mm radius and 153 mm length. From the results of the simulation study, it is found that total thrust increases linearly with magnetic field strength in the range of 0–0.1 T, but it decreases with increasing applied magnetic field up to 0.6 T. Thrust efficiency is found to increase to a maximum of 8.4% when B = 0.1 T; further, the peak value of nozzle efficiency reaches 91% at a moderate magnetic field (0.3 T). In detail, it is found that distributions of plasma density (10{sup 14}–10{sup 15} m{sup −3}) that form in the magnetic nozzle demonstrate a significant pattern of concentration up to fields of B = 0.3 T where ions begin to be magnetized. However, azimuthal velocities of ions behave differently with different degrees of magnetization, i.e., weakly magnetized ions follow rotating electrons in a right-handed direction, while fully magnetized ions revolve in left-handed direction due to electromagnetic forces. Notably, a feedback effect on total magnetic field due to plasma motion identified in other studies is not found to be present in the working conditions of the AF-MPDT examined here.

  16. Modeling of plasma processes in the slowly diverging magnetic fields at the exit of an applied-field magnetoplasmadynamic thruster

    NASA Astrophysics Data System (ADS)

    Li, Min; Tang, Hai-Bin; Ren, Jun-Xue; York, Thomas M.

    2013-10-01

    The performance of plasma thrusters with applied electric and magnetic fields can be enhanced by increasing the magnetic field strength, which is applied in the thrust chamber and the exit region propulsive plume. The ejected plasma which passes through a slowly diverging magnetic field will expand but can be restricted within the magnetic nozzle fields. To examine in detail the processes that occur, a new method with Particle-in-cell calculations is applied here. A two-dimensional axisymmetric particle dynamic code is used to model an AF-MPDT (Applied-field Magnetoplasmadynamic Thruster) for which extensive experimental data are available; it used Ar propellant and had applied magnetic coils of 101.5 mm radius and 153 mm length. From the results of the simulation study, it is found that total thrust increases linearly with magnetic field strength in the range of 0-0.1 T, but it decreases with increasing applied magnetic field up to 0.6 T. Thrust efficiency is found to increase to a maximum of 8.4% when B = 0.1 T; further, the peak value of nozzle efficiency reaches 91% at a moderate magnetic field (0.3 T). In detail, it is found that distributions of plasma density (1014-1015 m-3) that form in the magnetic nozzle demonstrate a significant pattern of concentration up to fields of B = 0.3 T where ions begin to be magnetized. However, azimuthal velocities of ions behave differently with different degrees of magnetization, i.e., weakly magnetized ions follow rotating electrons in a right-handed direction, while fully magnetized ions revolve in left-handed direction due to electromagnetic forces. Notably, a feedback effect on total magnetic field due to plasma motion identified in other studies is not found to be present in the working conditions of the AF-MPDT examined here.

  17. Can small earthquakes help understand lithospheric deformation in slowly deforming regions? A case study from Portugal, western Europe.

    NASA Astrophysics Data System (ADS)

    Custódio, Susana; Carrilho, Fernando; Gongóra, Eva; Marreiros, Célia; Rio, Inês; Silveira, Graça; Arroucau, Pierre; Dias, Nuno

    2015-04-01

    tools to study lithospheric deformation in slowly deforming regions, such as western Iberia.

  18. Splanchnic slowly adapting mechanoreceptors with punctate receptive fields in the mesentery and gastrointestinal tract of the cat

    PubMed Central

    Morrison, J. F. B.

    1973-01-01

    1. A class of slowly adapting mechanoreceptors with A-delta and C fibres running in the splanchnic nerves of cats is described. 2. The mechanoreceptors have punctate regions of mechanical sensitivity at macroscopic vascular branching points and have been found in the lesser omentum, the mesentery of the gall-bladder, porta hepatis, portal vein, pancreas, spleen and the duodenum, jejunum, ileum, colon and their mesenteries. 3. The receptive fields of these mechanoreceptors vary considerably in size in the different regions. The largest receptive fields were found in the small intestinal mesentery and consisted of up to seven points of mechanical sensitivity at vascular divisions, each separated by distances of a few up to about 40 mm. The smallest receptive fields were single or double points of mechanical sensitivity which were most commonly found in relation to the portal vein in the root of the mesentery. 4. Maintained stretch of the receptive field elicited a train of impulses which had phasic and tonic components. The tonic discharge was sometimes maintained for more than 1 min. 5. Distension of a neighbouring viscus often caused a discharge which had a phasic component and a variable tonic component. The occurrence of the latter appeared to depend on the relative positions of the bowel and mesentery, and was probably associated with a change in tension on the mesentery. 6. Occlusion of the portal vein resulted in some units in a discharge which began soon after the start of the occlusion. 7. The receptors do not appear to be affected by acid, hypoxia or hypercapnia. PMID:4747231

  19. On the possible existence of a self-regulating hydrodynamical process in slowly rotating stars. I. Setting the stage

    NASA Astrophysics Data System (ADS)

    Vauclair, Sylvie

    1999-11-01

    It has been known for a long time (Mestel 1953) that the meridional circulation velocity in stars, in the presence of displaystyle mu -gradients, is the sum of two terms, one due to the classical thermal imbalance (displaystyle Omega -currents) and the other one due to the induced horizontal displaystyle mu -gradients (displaystyle mu -induced currents, or displaystyle mu -currents in short). In the most general cases, displaystyle mu -currents are opposite to displaystyle Omega -currents. Simple expressions for these currents are derived under some simplifying physical assumptions presented in the text, and their physical interpretations are discussed. Computations of the displaystyle Omega and displaystyle mu -currents in a 0.8 Mdisplaystyle sun halo stellar model including classical element settling show that the displaystyle mu -currents are larger (in absolute values) than the displaystyle Omega -currents in all the star: some new physics has thus to be invoked in this case. We show here how such processes could possibly lead to a quasi-equilibrium stage in which both the circulation and the helium settling could be cancelled out. As lithium diffuses in the same way as helium, we expect a very small lithium concentration gradient below the convective zone in ``plateau stars'' (main-sequence Pop II stars), much smaller than the one expected for pure element settling. This could possibly account for the very small dispersion observed for the lithium abundances at the surface of these stars. This should also have important consequences in other contexts which will be discussed in forthcoming papers. The present computations show that element settling in slowly rotating stars leads to surface abundances which depend on the competition between displaystyle mu -currents and displaystyle Omega -currents, in a way which had not been taken into account in previous computations. This may change our general understanding of the diffusion processes of chemical species in

  20. Slowly ascending magmas in long-lived accretionary orogens: unraveling temporal variations in the Cordilleran-style Sveconorwegian Orogeny

    NASA Astrophysics Data System (ADS)

    Bybee, G. M.; Slagstad, T.; Roberts, N. M. W.; Coint, N.; Ashwal, L. D.

    2015-12-01

    Southwestern Norway is host to spatially associated magmatic provinces that have been interpreted as magmatic products of the Sveconorwegian Orogeny. The Sirdal Magmatic Belt (SMB) and the Hornblende-Biotite Granite (HBG) Suite were emplaced between 1050-1020 Ma and 980-930 Ma, respectively. Geochronology of the Rogaland Anorthosite Province (RAP) indicates that magmatism began at 1041 Ma (high pressure, cogenetic megacrysts) and culminated in anorthosite emplacement at ±930 Ma. Decompression exsolution ages for these high-P megacrysts indicate that decompression during anorthosite ascent took place ±80-100 m.y. after crystallization at the Moho. The contact aureole of the RAP shows concordant arrays of zircon ages between 1050-930 Ma, recording continuous, long-lived high temperature magmatic events in southwestern Norway. Zircon ages from outside the contact aureole show a metamorphic event at ±1035 Ma, but show no younger concordant arrays. Metapelites from the contact aureole of the RAP also show a spread of monazite ages, where monazite inclusions in garnet record ages of 1038-992 Ma, while groundmass monazite preserve ages of 952±10 Ma, indicative of multiple and/or long-lived thermal events. Age coincidence for several events, including matrix monazite formation, megacryst decompression (and anorthosite emplacement) and HBG granite crystallization suggest a dynamic system with multiple feedback loops. Varying isotopic signatures recorded in the region hint at changing sources and processes associated with the genesis of the magmas. These observations indicate that the Sveconorwegian orogeny was a long-lived magmatic system that featured slowly ascending magmas, punctuated periods of magmatism and temporal geochemical variation - features analogous to younger Cordilleran systems. When estimating magmatic tempos in arc environments, factors such as large degrees of differentiation in the lower crust, polybaric magma evolution and slow magma ascent rates

  1. How dominant is the most efficient pathway through the potential energy landscape of a slowly diffusing disordered system?

    PubMed

    Nguyen, Crystal N; Isaacson, Joseph I; Shimmyo, Kayoko Beth; Chen, Andersen; Stratt, Richard M

    2012-05-14

    It has been suggested that the most-efficient pathway taken by a slowly diffusing many-body system is its geodesic path through the parts of the potential energy landscape lying below a prescribed value of the potential energy. From this perspective, slow diffusion occurs just because these optimal paths become particularly long and convoluted. We test this idea here by applying it to diffusion in two kinds of well-studied low-dimensional percolation problems: the 2d overlapping Lorentz model, and square and simple-cubic bond-dilute lattices. Although the most efficient path should be at its most dominant with the high-dimensional landscapes associated with many-body problems, it is useful to examine simpler, low-dimensional, constant-potential-energy problems such as these ones, both because the simpler models lend themselves to more accurate geodesic-path-finding approaches, and because they offer a significant contrast to many of the models used in the traditional energy-landscape literature. Neither the continuum nor the lattice percolation examples are adequately described by our geodesic-path formalism in the weakly disordered (relatively-fast-diffusion) limit, but in both cases the formalism successfully predicts the existence of the percolation transition and (to a certain extent) the slow diffusion characteristic of near-percolation behavior. The numerical results for these models are not nearly accurate enough near their transitions to describe critical exponents, but the models do showcase the qualitative validity of the geodesic perspective in that they allow us to see explicitly how tortuous and sparse the optimal pathways become as the diffusion constants begin to vanish. PMID:22583297

  2. Progressive hemifacial atrophy. A natural history study.

    PubMed Central

    Miller, M T; Spencer, M A

    1995-01-01

    PURPOSE: To describe two very different natural history courses in 2 patients with hemifacial atrophy. Progressive hemifacial atrophy (Parry-Romberg syndrome, Romberg syndrome, PHA) is characterized by slowly progressive atrophy, frequently involving only one side of the face, primarily affecting the subcutaneous tissue and fat. The onset usually occurs during the first 2 decades of life. The cause and pathophysiology are unknown. Ophthalmic involvement is common, with progressive enophthalmos a frequent finding. Pupillary disturbances, heterochromia, uveitis, pigmentary disturbances of the ocular fundus, and restrictive strabismus have also been reported. Neurologic findings may be present, but the natural history and progression of ocular findings are often not described in the literature. METHODS: We studied the records and present findings of 2 patients with progressive hemifacial atrophy who were observed in our institution over a 10-year period. RESULTS: Both patients showed progression of ophthalmic findings, primarily on the affected side. One patient has had chronic uveitis with secondary cataract and glaucoma, in addition to retinal pigmentary changes. She also had a third-nerve paresis of the contralateral eye and mild seizure activity. The other patient had mild uveitis, some progression of unilateral retinal pigmentary changes, and a significant increase in hyperopia in the affected eye, in addition to hypotony at age 19 without a clear cause, but with secondary retinal and refractive changes. CONCLUSION: Ocular manifestations of progressive hemifacial atrophy are varied, but can progress from mild visual impairment to blindness. Images FIGURE 1 FIGURE 2 FIGURE 3A FIGURE 3B FIGURE 4 FIGURE 5 FIGURE 6 PMID:8719679

  3. Rapid susceptibility testing for slowly growing nontuberculous mycobacteria using a colorimetric microbial viability assay based on the reduction of water-soluble tetrazolium WST-1.

    PubMed

    Tsukatani, T; Suenaga, H; Shiga, M; Ikegami, T; Ishiyama, M; Ezoe, T; Matsumoto, K

    2015-10-01

    Rapid susceptibility testing for slowly growing nontuberculous mycobacteria (NTM) using a colorimetric microbial viability assay based on the reduction of the water-soluble tetrazolium salt {2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-1)} using 2,3,5,6-tetramethyl-1,4-benzoquinone as an electron mediator was developed. Using the Clinical and Laboratory Standards Institute (CLSI) method, a long-term incubation time (7-14 days) was required to determine the minimum inhibitory concentrations (MICs) of the slowly growing NTM. The MICs for a variety of different antibiotics against the slowly growing NTM were determined by the WST-1 colorimetric method and compared with those obtained using the broth microdilution methods approved by the CLSI. Good agreement was found between the MICs determined after 3-4 days using the WST-1 colorimetric method and those obtained after 10-14 days using the broth microdilution method. The results suggest that the WST-1 colorimetric assay is a useful method for the rapid determination of the MICs for the slowly growing NTM. PMID:26173690

  4. Progressive loss of speech output and orofacial dyspraxia associated with frontal lobe hypometabolism.

    PubMed Central

    Tyrrell, P J; Kartsounis, L D; Frackowiak, R S; Findley, L J; Rossor, M N

    1991-01-01

    Three patients are described with slowly progressive loss of speech and dysarthria associated with orofacial dyspraxia, initially with intact written language, who subsequently developed more widespread cognitive abnormalities. Positron emission tomography (PET) revealed bifrontal hypometabolism in all of the patients, most marked in the inferior and lateral portions of both frontal lobes, with some extension into the parietal and temporal cortices in one case. These patients may represent a further example of focal progressive cortical degeneration. Images PMID:2056322

  5. Selective blockade of a slowly inactivating potassium current in striatal neurons by (+/-) 6-chloro-APB hydrobromide (SKF82958).

    PubMed

    Nisenbaum, E S; Mermelstein, P G; Wilson, C J; Surmeier, D J

    1998-07-01

    The ion channels of rat striatal neurons are known to be modulated by stimulation of D1 dopamine receptors. The susceptibility of depolarization-activated K+ currents to be modulated by the D1 agonist, 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzaze pine (APB) was investigated using whole-cell voltage-clamp recording techniques from acutely isolated neurons. APB (0.01-100 microM) produced a concentration-dependent reduction in the total K+ current. At intermediate concentrations (ca. 10 microM), APB selectively depressed the slowly inactivating A-current (I(As)). A similar effect was produced by application of the D1 agonist, 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1-H-2-benzazepine (SKF38393, 10 microM). APB reduced I(As) rapidly, having onset and recovery time constants of 1.2 sec and 1.6 sec, respectively. Unexpectedly, the effect of APB could not be mimicked by application of Sp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Sp-cAMPS, 100-200 microM), a membrane-permeable analog of cyclic AMP (cAMP), or by pretreatment with forskolin (25 microM), an activator of adenylyl cyclase. The reduction in I(As) also was not blocked by pretreatment with the D1 receptor antagonist, R(+)-SCH23390 hydrochloride (SCH23390, 10-20 microM). In addition, intracellular dialysis with guanosine-5'-O-(2-thiodiphosphate (GDP-beta-S, 200 microM) did not preclude the APB-induced inhibition of I(As), nor did dialysis with guanosine-5'-O-(3-thiotriphosphate (GTP-gamma-S, 400 microM) prevent reversal of the effect. The effect of APB was produced by a reduction in the maximal conductance of I(As) without changing the voltage-dependence of the current. Collectively, these results argue that APB does not inhibit I(As) through D1 receptors coupled to stimulation of adenylyl cyclase, but rather by allosterically regulating or blocking the channels giving rise to this current. PMID:9635891

  6. Progress in Enzyme Replacement Therapy in Glycogen Storage Disease Type II.

    PubMed

    Angelini, Corrado; Semplicini, Claudio; Tonin, Paola; Filosto, Massimiliano; Pegoraro, Elena; Sorarù, Gianni; Fanin, Marina

    2009-05-01

    Glycogen storage disease type II (GSDII) is an autosomal recessive lysosomal disorder caused by mutations in the gene encoding alpha-glucosidase (GAA). The disease can be clinically classified into three types: a severe infantile form, a juvenile and an adultonset form. Cases with juvenile or adult onset GSDII mimic limb-girdle muscular dystrophy or polymyositis and are often characterized by respiratory involvement. GSDII patients are diagnosed by biochemical assay and by molecular characterization of the GAA gene. Ascertaining a natural history of patients with heterogeneous late-onset GSDII is useful for evaluating their progressive functional disability. A significant decline is observed over the years in skeletal and respiratory muscle function. Enzyme replacement therapy (ERT) has provided encouraging results in the infantile form. It is not yet known if ERT is effective in late-onset GSDII. We examined a series of 11 patients before and after ERT evaluating muscle strength by MRC, timed and graded functional tests, 6-minute walk test (6MWT), respiratory function by spirometric parameters and quality of life. We observed a partial improvement during a prolonged follow-up from 3 to 18 months. The use of different clinical parameters in the proposed protocol seems crucial to determine the efficacy of ERT, since not all late-onset patients respond similarly to ERT. PMID:21179524

  7. EP 171: a high affinity thromboxane A2-mimetic, the actions of which are slowly reversed by receptor blockade.

    PubMed Central

    Jones, R. L.; Wilson, N. H.; Lawrence, R. A.

    1989-01-01

    1. Replacement of the four-carbon omega-terminus in 9,11-endoxy-10a-homo prostaglandin H2 with a p-fluorophenoxy group produces a compound (EP 171) with very high agonist potency at TP-receptors. 2. On six isolated smooth muscle preparations EP 171 was 33-167 times more potent as a TP-receptor agonist than U-46619 (11,9-epoxymethano PGH2); EC50 values ranged from 45 to 138 pM. The actions of EP 171 were difficult to study because of their slow onset and offset. For example, on the guinea-pig trachea the time required for 50% reversal of EP 171-induced contractions during washout was about 3 h. 3. On the pig pulmonary artery, a more rapidly responding preparation, it was possible to show that the TP-receptor antagonist EP 092 blocked the contractile actions of EP 171 and U-46619 to similar extents: pA2 = 8.09 and 8.15 respectively. 4. EP 171 was also a very potent activator of human blood platelets, being about 90 times more potent than U-46619. Both shape change (0.1 nM) and aggregation (1 nM) were slow in onset, a profile not previously observed for a thromboxane A2-mimetic. 5. When potencies at TP-, EP1-(guinea-pig fundus) and FP-(dog iris sphincter) receptors were compared, EP 171 showed a higher specificity as a TP-receptor agonist than either STA2 or U-46619. These studies also showed that contrary to earlier reports, the guinea-pig fundus does contain TP-receptors mediating muscle contraction. However, the maximal response due to activation of TP-receptors was only about 35% of the PGE2 maximum. 6. Established responses to EP 171 were slowly reversed following addition of a high concentration of a TP-receptor antagonist (EP 092, GR 32191 or BM 13177). Faster reversals of three less potent 16-p-halophenoxy prostanoids and U-46619 were obtained. Half-times for offset (and onset) of agonist action appeared to correlate with potency rather than with lipophilicity. 7. Competition between the agonists and a radio iodinated PTA2 derivative ([125I]-PTA-OH) for

  8. Interrupted or continuous slowly absorbable sutures – Design of a multi-centre randomised trial to evaluate abdominal closure techniques INSECT-Trial [ISRCTN24023541

    PubMed Central

    Knaebel, Hanns-Peter; Koch, Moritz; Sauerland, Stefan; Diener, Markus K; Büchler, Markus W; Seiler, Christoph M

    2005-01-01

    Background The closure of the abdomen after median laparotomy is still a matter of debate among surgeons. Further well designed and performed randomised controlled trials determining the optimal method of abdominal fascial closure are needed. Design This is a three armed, multi-centre, intra-operatively randomised, controlled, patient blinded trial. Over 20 surgical departments will enrol 600 patients who are planned for an elective primary abdominal operation. The objective of this study is to compare the frequency of abdominal incisional hernias between two continuous suture techniques with different, slowly absorbable monofilament materials and an interrupted suture using an absorbable braided suture material at one year postoperatively. Conclusion This trial will answer the question whether the continuous abdominal wall closure with a slowly absorbable material with longitudinal elasticity is superior to the continuous suture with a material lacking elasticity and to interrupted sutures with braided thread. PMID:15755324

  9. Chromosome replication during the division cycle in slowly growing, steady-state cultures of three Escherichia coli B/r strains.

    PubMed Central

    Kubitschek, H E; Newman, C N

    1978-01-01

    The period of DNA synthesis C during the cell cycle was determined over a broad range of generation times in slowly growing, steady-state batch cultures in the exponential phase and in chemostat cultures of three strains of Escherichia coli, strains B/r A, B/r K, and B/r TT, utilizing measurements of average amounts of DNA per cell and cell survival after radioactive decay of 125I incorporated into the DNA of synthesizing cells. At each growth rate, values for cell survival and for C periods were the same within experimental errors for the three strains. The length of the DNA synthesis period increased linearly with generation (doubling) time T of the culture and approached a limiting value of C = 0.36T at very long generation times. In very slowly growing cultures, DNA replication was limited almost entirely to the final third of the cell cycle. D periods, between termination of DNA replication and cell division, were found to be relatively short at all growth rates for each strain. Average amounts of DNA per cell measured in slowly growing cultures of strains B/r A and B/r TT were indistinguishable from results for strain B/r K at the same growth rates. Amounts of DNA per cell calculated from the cell survival values alone are completely consistent with the measured DNA per cell. PMID:361687

  10. EDITORIAL: Catalysing progress Catalysing progress

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  11. EDITORIAL: Catalysing progress Catalysing progress

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  12. Chronologic Presentation of a Severe Case of Progressive Hemifacial Atrophy (Parry-Romberg Syndrome) with the Loss of an Eye

    PubMed Central

    Kaya, Mesut; Sel Yilmaz, Ceyda; Kurtaran, Hanifi; Gunduz, Mehmet

    2014-01-01

    Progressive hemifacial atrophy, also known as Parry-Romberg syndrome, is a slowly advancing degenerative disease that mostly affects the cutaneous, subcutaneous fatty tissue, muscle tissue, and bone structures on one side of the face. We describe the chronological progression of this very rare syndrome from early childhood until adulthood in a patient who developed severe atrophy and lost one eye. We also discuss the aetiology and pathophysiology of this syndrome. PMID:25506017

  13. Slowly digestible starch influences mRNA abundance of glucose and short-chain fatty acid transporters in the porcine distal intestinal tract.

    PubMed

    Woodward, A D; Regmi, P R; Gänzle, M G; van Kempen, T A T G; Zijlstra, R T

    2012-12-01

    The relationship between starch chemistry and intestinal nutrient transporters is not well characterized. We hypothesized that inclusion of slowly instead of rapidly digestible starch in pig diets will decrease glucose and increase short-chain fatty acid (SCFA) transporter expression in the distal gut. Weaned barrows (n = 32) were fed 4 diets containing 70% starch [ranging from 0 to 63% amylose and from 1.06 (rapidly) to 0.22%/min (slowly) rate of in vitro digestion] at 3 × maintenance energy requirement in a complete randomized block design. Ileal and colon mucosa was collected on day 21 to quantify mRNA abundance of Na(+)-dependent glucose transporter 1 (SGLT1), monocarboxylic acid transporter 1 (MCT1), and Na(+)-coupled monocarboxylate transporter (SMCT). Messenger RNA was extracted and cDNA manufactured prior to relative quantitative reverse transcription PCR. Data were analyzed using the 2(-Δ ΔC)(T) method, with β-actin and glyceraldehyde-3-phosphate dehydrogenase as reference genes, and regression analysis was performed. As in vitro rate of digestion decreased, SGLT1 linearly increased (P < 0.05) in the ileum. Contrary to SGLT1, MCT1 tended to linearly decrease (P = 0.08) in the ileum and increased quadratically (P < 0.001) in the colon with decreasing rate of digestion. Starch digestion rate did not affect SMCT in the ileum; however, colonic SMCT quadratically decreased (P < 0.01) with decreasing rate of digestion. In conclusion, in contrast to our hypothesis, slowly digestible starch increased ileal glucose and decreased ileal SCFA transporter mRNA abundance, possibly due to an increased glucose in the luminal ileum. Effects of starch on colonic SCFA transporter mRNA abundance were inconsistent. PMID:23365289

  14. Effects of transient receptor potential (TRP) channel agonists and antagonists on slowly adapting type II mechanoreceptors in the rat sinus hair follicle.

    PubMed

    Cahusac, Peter M B

    2009-12-01

    The possible functional role of transient receptor potential (TRP) channels was investigated by testing various TRP agonists and antagonists in an isolated rat sinus hair follicle preparation. Extracellular recordings from slowly adapting type II mechanoreceptor units were made. The antagonist capsazepine depressed spontaneous and mechanically evoked activity, with an IC(50) of 82 microM. In one-third of units, capsazepine caused a selective depression of mechanically evoked firing, such that the existing spontaneous firing was interrupted by an absence of activity during the mechanical stimulus. The broad spectrum TRP blocker ruthenium red (30 microM) had inconsistent effects, although in some units a delayed onset (following wash) bursting and paroxysmal firing ensued. The agonist icilin (50-100 microM) had an excitatory effect on spontaneous firing, and (-)-menthol (200 microM) had inconsistent effects. Cinnamaldehyde (1-2 mM) depressed all types of activity equally, mechanically evoked and spontaneous. Camphor (0.5-2 mM) also depressed all types of activity, although it had a preferential effect on spontaneous activity. Capsaicin (1-10 microM) and allyl isothiocyanate (50-100 microM) had no clear effects. These results rule out any role for TRPA1 and TRPV1 channels in mechanotransduction processes of slowly adapting type II mechanoreceptors. PMID:20021572

  15. Childhood dyspraxia predicts adult-onset nonaffective-psychosis-spectrum disorder.

    PubMed

    Schiffman, Jason; Mittal, Vijay; Kline, Emily; Mortensen, Erik L; Michelsen, Niels; Ekstrøm, Morten; Millman, Zachary B; Mednick, Sarnoff A; Sørensen, Holger J

    2015-11-01

    Several neurological variables have been investigated as premorbid biomarkers of vulnerability for schizophrenia and other related disorders. The current study examined whether childhood dyspraxia predicted later adult nonaffective-psychosis-spectrum disorders. From a standardized neurological examination performed with children (aged 10-13) at genetic high risk of schizophrenia and controls, several measures of dyspraxia were used to create a scale composed of face/head dyspraxia, oral articulation, ideomotor dyspraxia (clumsiness), and dressing dyspraxia (n = 244). Multinomial logistic regression showed higher scores on the dyspraxia scale predict nonaffective-psychosis-spectrum disorders relative to other psychiatric disorders and no mental illness outcomes, even after controlling for genetic risk, χ2 (4, 244) = 18.61, p < .001. Findings that symptoms of dyspraxia in childhood (reflecting abnormalities spanning functionally distinct brain networks) specifically predict adult nonaffective-psychosis-spectrum disorders are consistent with a theory of abnormal connectivity, and they highlight a marked early-stage vulnerability in the pathophysiology of nonaffective-psychosis-spectrum disorders. PMID:26439077

  16. Adult-onset cystic hygroma: A case report of rare entity.

    PubMed

    Bahl, Sumit; Shah, Vandana; Anchlia, Sonal; Vyas, Siddharth

    2016-01-01

    Cystic hygroma is a benign congenital malformation of the lymphatic system that occurs in infant or children younger than 2 years of age. Although cystic hygroma is well recognized in pediatric practice, it seldom presents de novo in adulthood. These are commonly present in head and neck but can be present anywhere. Cystic hygroma is very rare in adults, but it should be considered in the differential diagnosis of adult neck swellings. Patients presenting with a painless, soft, fluctuant, and enlarging neck mass should have a careful history and physical examination along with radiological imaging to assist with diagnosis. Surgical intervention is the treatment of choice for this rare condition. Here, we are reporting a case of cystic hygroma in a 32-year-old male patient in the neck region. The objectives of this case report are to discuss the clinical presentation, diagnosis, histopathological findings and management of this malformation. PMID:27134456

  17. Delineation of Early and Later Adult Onset Depression by Diffusion Tensor Imaging

    PubMed Central

    Yu, Hongjun; Nie, Binbin; Li, Na; Luo, Chunrong; Li, Haijun; Liu, Fang; Bai, Yan; Shan, Baoci; Xu, Lin; Xu, Xiufeng

    2014-01-01

    Background Due to a lack of evidence, there is no consistent age of onset to define early onset (EO) versus later onset (LO) major depressive disorder (MDD). Fractional anisotropy (FA), derived from diffusion tensor imaging (DTI), has been widely used to study neuropsychiatric disorders by providing information about the brain circuitry, abnormalities of which might facilitate the delineation of EO versus LO MDD. Method In this study, 61 pairs of untreated, non-elderly, first-episode MDD patients and healthy controls (HCs) aged 18–45 years old received DTI scans. The voxel-based analysis method (VBM), classification analysis, using the Statistical Package for the Social Sciences (SPSS), and regression analyses were used to determine abnormal FA clusters and their correlations with age of onset and clinical symptoms. Results Classification analysis suggested in the best model that there were two subgroups of MDD patients, delineated by an age of onset of 30 years old, by which MDD patients could be divided into EO (18–29 years old) and LO (30–45 years old) groups. LO MDD was characterized by decreased FA, especially in the white matter (WM) of the fronto-occipital fasciculus and posterior limb of internal capsule, with a negative correlation with the severity of depressive symptoms; in marked contrast, EO MDD showed increased FA, especially in the WM of the corpus callosum, corticospinal midbrain and inferior fronto-occipital fasciculus, while FA of the WM near the midbrain had a positive correlation with the severity of depressive symptoms. Conclusion Specific abnormalities of the brain circuitry in EO vs. LO MDD were delineated by an age of onset of 30 years old, as demonstrated by distinct abnormal FA clusters with opposite correlations with clinical symptoms. This DTI study supported the evidence of an exact age for the delineation of MDD, which could have broad multidisciplinary importance. Trial Registration ClinicalTrials.gov NCT00703742 PMID:25393297

  18. Adult-onset cystic hygroma: A case report of rare entity

    PubMed Central

    Bahl, Sumit; Shah, Vandana; Anchlia, Sonal; Vyas, Siddharth

    2016-01-01

    Cystic hygroma is a benign congenital malformation of the lymphatic system that occurs in infant or children younger than 2 years of age. Although cystic hygroma is well recognized in pediatric practice, it seldom presents de novo in adulthood. These are commonly present in head and neck but can be present anywhere. Cystic hygroma is very rare in adults, but it should be considered in the differential diagnosis of adult neck swellings. Patients presenting with a painless, soft, fluctuant, and enlarging neck mass should have a careful history and physical examination along with radiological imaging to assist with diagnosis. Surgical intervention is the treatment of choice for this rare condition. Here, we are reporting a case of cystic hygroma in a 32-year-old male patient in the neck region. The objectives of this case report are to discuss the clinical presentation, diagnosis, histopathological findings and management of this malformation. PMID:27134456

  19. Adult onset-hypothyroidism increases response latency and long-term potentiation (LTP) in rat hippocampus

    EPA Science Inventory

    Thyroid hormones (TH) influence central nervous system (CNS) function during both development and in adulthood. The hippocampus is critical for some types of learning and memory and is particularly sensitive to thyroid hormone deficiency. Hypothyroidism in adulthood has been ass...

  20. Epigenetics as the mediator of fetal programming of adult onset disease: what is the evidence?

    PubMed

    Saffery, Richard; Novakovic, Boris

    2014-11-01

    The Developmental Origins of Health and Disease hypothesis describes how early life environmental factors influence development in a way that impacts later health and disease risk. The hypothesis is supported by a large number of animal studies and a smaller number of observational studies in humans. Epigenetic variation induced in early life has emerged as a prime candidate to be the mediator of such effects, but little direct evidence of this relation exists in humans, primarily due to the inherent problems associated with unraveling the relative contributions of genetic and environmental variables to phenotypic diversity. There are several prerequisites for establishing a causal link that include demonstrating interindividual epigenetic variability in early life in response to specific environmental exposures. Further, compelling evidence linking epigenetic change to disease, prior to onset is required. Finally, the functional relevance of specific epigenetic change must be demonstrated. Evidence is emerging in all of these areas but, ultimately, only large longitudinal life-course studies, commencing prior to birth, can provide direct evidence in support of a role of epigenetic processes as a driver of Developmental Origins of Health and Disease in humans. PMID:24835110

  1. Adult Onset Global Loss of the Fto Gene Alters Body Composition and Metabolism in the Mouse

    PubMed Central

    Wells, Sara; Teboul, Lydia; Tung, Y. C. Loraine; Rimmington, Debra; Bosch, Fatima; Jimenez, Veronica; Yeo, Giles S. H.; O'Rahilly, Stephen; Ashcroft, Frances M.; Coll, Anthony P.; Cox, Roger D.

    2013-01-01

    The strongest BMI–associated GWAS locus in humans is the FTO gene. Rodent studies demonstrate a role for FTO in energy homeostasis and body composition. The phenotypes observed in loss of expression studies are complex with perinatal lethality, stunted growth from weaning, and significant alterations in body composition. Thus understanding how and where Fto regulates food intake, energy expenditure, and body composition is a challenge. To address this we generated a series of mice with distinct temporal and spatial loss of Fto expression. Global germline loss of Fto resulted in high perinatal lethality and a reduction in body length, fat mass, and lean mass. When ratio corrected for lean mass, mice had a significant increase in energy expenditure, but more appropriate multiple linear regression normalisation showed no difference in energy expenditure. Global deletion of Fto after the in utero and perinatal period, at 6 weeks of age, removed the high lethality of germline loss. However, there was a reduction in weight by 9 weeks, primarily as loss of lean mass. Over the subsequent 10 weeks, weight converged, driven by an increase in fat mass. There was a switch to a lower RER with no overall change in food intake or energy expenditure. To test if the phenotype can be explained by loss of Fto in the mediobasal hypothalamus, we sterotactically injected adeno-associated viral vectors encoding Cre recombinase to cause regional deletion. We observed a small reduction in food intake and weight gain with no effect on energy expenditure or body composition. Thus, although hypothalamic Fto can impact feeding, the effect of loss of Fto on body composition is brought about by its actions at sites elsewhere. Our data suggest that Fto may have a critical role in the control of lean mass, independent of its effect on food intake. PMID:23300482

  2. The clinical implications of adult-onset henoch-schonelin purpura

    PubMed Central

    2011-01-01

    Henoch-Schonlein Purpura (HSP) is a small vessel vasculitis mediated by IgA-immune complex deposition. It is characterized by the clinical tetrad of non-thrombocytopenic palpable purpura, abdominal pain, arthritis and renal involvement. Pathologically, it can be considered a form of immune complex-mediated leukocytoclastic vasculitis (LCV) involving the skin and other organs. Though it primarily affects children (over 90% of cases), the occurrence in adults has been rarely reported. Management often involves the use of immunomodulatory or immune-suppressive regimens. PMID:21619657

  3. An adult onset case of alpha-methyl-acyl-CoA racemase deficiency.

    PubMed

    Smith, Emily Helen; Gavrilov, Dimitar K; Oglesbee, Devin; Freeman, William D; Vavra, Michael W; Matern, Dietrich; Tortorelli, Silvia

    2010-12-01

    α-Methyl-acyl-CoA-racemase (AMACR) deficiency (OMIM 604489) is a rare peroxisomal disorder with a variable age of onset from infancy to late adulthood. We describe a 45-year-old male with a history of seizures who presented with relapsing encephalopathy. Laboratory studies revealed an elevated serum pristanic acid concentration, an elevated pristanic/phytanic acid ratio, as well as the previously described homozygous mutation in the AMACR gene, c.154T>C, consistent with AMACR deficiency. This homozygous mutation is associated with a variable phenotype ranging from neonatal cholestasis to late-onset sensorimotor neuropathy. Dietary pristanic acid restriction was attempted to improve clinical status and the patient has remained in remission for more than 16 months. PMID:20821052

  4. Adult onset asynchronous multifocal eosinophilic granuloma of bone: an 11-year follow-up

    PubMed Central

    Dallaudière, Benjamin; Kerger, Joseph; Malghem, Jacques; Galant, Christine

    2015-01-01

    Multifocal eosinophilic granuloma (EG) is a rare observation within the spectrum of histiocytosis X, generally described in children. We report the case of a 33-year-old man with multifocal EG showing an asynchronous evolution of bone lesions during a follow-up of 11 years. We also present the therapeutic approach chosen for this patient and the repeated magnetic resonance imaging (MRI) examinations used to monitor the disease with a final favorable outcome. PMID:25793108

  5. Work Place Success for Persons with Adult-Onset Hearing Impairment.

    ERIC Educational Resources Information Center

    Glass, Laurel E.; Elliott, Holly

    1993-01-01

    Data from 1,309 persons who were working and became hard of hearing or deafened between the ages of 18 and 65 are analyzed to determine work outcomes in terms of occupation, perception of work achievement, earning power, support of supervisors and colleagues, and work adaptations. Data show that work success is possible and usual after…

  6. Adult-onset Invasive Haemophilus influenzae Type f Caused by Acute Lower Leg Cellulitis.

    PubMed

    Usui, Yuko; Kakuta, Risako; Araki, Makoto; Sato, Taigo; Gu, Yoshiaki; Yano, Hisakazu; Taniuchi, Norihide

    2016-01-01

    In Japan, routine Haemophilus influenzae type b (Hib) vaccination began in 2013. Thus, similar to other countries, a strain shift is expected in the near future. We experienced a case of H. influenzae type f (Hif) bacteremia in a 66-year-old man. The primary focus of the infection was the soft tissue of the left lower leg, which is an extremely rare origin in adults. Subsequently, we conducted multilocus sequence typing and identified the strain as sequence type 124, which is the most common invasive strain of Hif worldwide. This case may mark the beginning of an Hif strain shift in Japan. PMID:27374690

  7. Adult onset motor neuron disease: worldwide mortality, incidence and distribution since 1950.

    PubMed Central

    Chancellor, A M; Warlow, C P

    1992-01-01

    This review examines the commonly held premise that, apart from the Western Pacific forms, motor neuron disease (MND), has a uniform worldwide distribution in space and time; the methodological problems in studies of MND incidence; and directions for future epidemiological research. MND is more common in men at all ages. Age-specific incidence rises steeply into the seventh decade but the incidence in the very elderly is uncertain. A rise in mortality from MND over recent decades has been demonstrated wherever this has been examined and may be real rather than due to improved case ascertainment. Comparison of incidence studies in different places is complicated by non-standardised methods of case ascertainment and diagnosis but there appear to be differences between well studied populations. In developed countries in the northern hemisphere there is a weak positive correlation between standardised, age-specific incidence and distance from the equator. There is now strong evidence for an environmental factor as the cause of the Western Pacific forms of MND. A number of clusters of sporadic MND have been reported from developed countries, but no single agent identified as responsible. Images PMID:1479386

  8. Sciatic nerve regeneration in mice and rats: recovery of sensory innervation is followed by a slowly retreating neuropathic pain-like syndrome.

    PubMed

    Vogelaar, Christina F; Vrinten, Dorien H; Hoekman, Marco F M; Brakkee, Jan H; Burbach, J Peter H; Hamers, Frank P T

    2004-11-19

    Peripheral nerve regeneration has been studied extensively in the sciatic nerve crush model, at the level of both function and gene expression. The crush injury allows full recovery of sensory and motor function in about 3 weeks as assessed by the foot reflex withdrawal test and De Medinacelli walking patterns. We used the recently developed CatWalk paradigm to study walking patterns in more detail in mice and rats. We found that, following the recovery of sensory function, the animals developed a state of mechanical allodynia, which retreated slowly over time. The motor function, although fully recovered with the conventional methods, was revealed to be still impaired because the animals did not put weight on their previously injured paw. The development of neuropathic pain following successful sensory recovery has not been described before in crush-lesioned animals and may provide an important new parameter to assess full sensory recovery. PMID:15494158

  9. IMPLICATIONS OF BURST OSCILLATIONS FROM THE SLOWLY ROTATING ACCRETING PULSAR IGR J17480-2446 IN THE GLOBULAR CLUSTER TERZAN 5

    SciTech Connect

    Cavecchi, Y.; Patruno, A.; Haskell, B.; Watts, A. L.; Altamirano, D.; Wijnands, R.; Van der Klis, M.; Levin, Y.; Linares, M.

    2011-10-10

    The recently discovered accreting X-ray pulsar IGR J17480-2446 spins at a frequency of {approx}11 Hz. We show that Type I X-ray bursts from this source display oscillations at the same frequency as the stellar spin. IGR J17480-2446 is the first secure case of a slowly rotating neutron star (NS) which shows Type I burst oscillations (BOs), all other sources featuring such oscillations spin at hundreds of Hertz. This means that we can test BO models in a completely different regime. We explore the origin of Type I BOs in IGR J17480-2446 and conclude that they are not caused by global modes in the NS ocean. We also show that the Coriolis force is not able to confine an oscillation-producing hot spot on the stellar surface. The most likely scenario is that the BOs are produced by a hot spot confined by hydromagnetic stresses.

  10. Neotectonics and seismicity of a slowly deforming segment of the Adria-Europe convergence zone - the northern Dinarides fold-and-thrust belt

    NASA Astrophysics Data System (ADS)

    Ustaszewski, Kamil; Herak, Marijan; Tomljenović, Bruno; Herak, Davorka; Matej, Srebrenka

    2014-05-01

    With GPS-derived shortening rates of c. 3-5 mm/a, the Adria-Europe convergence zone across the fold-and-thrust belt of the Dinarides (Balkan Peninsula) is a slowly deforming plate boundary by global standards. We have analysed the active tectonics and instrumental seismicity of the northernmost segment of this fold-and-thrust belt at its border to the Pannonian Basin. This area hosts a Maastrichtian collisional suture formed by closure of Mesozoic fragments of the Neotethys, overprinted by Miocene back-arc extension, which led to the exhumation of greenschist- to amphibolite-grade rocks in several core complexes. Geological, geomorphological and reflection seismic data provide evidence for a compressive or transpressive reactivation of extensional faults after about 5 Ma. The study area represents the seismically most active region of the Dinarides apart from the Adriatic Sea coast and the area around Zagreb. The strongest instrumentally recorded earthquake (27 October 1969) affected the city of Banja Luka (northern Bosnia and Herzegovina). Fault plane solutions for the main shock (ML 6.4) and its largest foreshock (ML 6.0) indicate reverse faulting along ESE-WNW-striking nodal planes and generally N-S trending pressure axes. The spatial distribution of epicentres and focal depths, analyses of the macroseismic field and fault-plane solutions for several smaller events suggest on-going shortening in the internal Dinarides. Our results therefore imply that current Adria-Europe convergence is widely distributed across c. 300 km, rendering the entire Dinarides fold-and-thrust belt a slowly deforming plate boundary.

  11. Differentiation of Phylogenetically Related Slowly Growing Mycobacteria Based on 16S-23S rRNA Gene Internal Transcribed Spacer Sequences

    PubMed Central

    Roth, Andreas; Fischer, Marga; Hamid, Mohamed E.; Michalke, Sabine; Ludwig, Wolfgang; Mauch, Harald

    1998-01-01

    Interspecific polymorphisms of the 16S rRNA gene (rDNA) are widely used for species identification of mycobacteria. 16S rDNA sequences, however, do not vary greatly within a species, and they are either indistinguishable in some species, for example, in Mycobacterium kansasii and M. gastri, or highly similar, for example, in M. malmoense and M. szulgai. We determined 16S-23S rDNA internal transcribed spacer (ITS) sequences of 60 strains in the genus Mycobacterium representing 13 species (M. avium, M. conspicuum, M. gastri, M. genavense, M. kansasii, M. malmoense, M. marinum, M. shimoidei, M. simiae, M. szulgai, M. triplex, M. ulcerans, and M. xenopi). An alignment of these sequences together with additional sequences available in the EMBL database (for M. intracellulare, M. phlei, M. smegmatis, and M. tuberculosis) was established according to primary- and secondary-structure similarities. Comparative sequence analysis applying different treeing methods grouped the strains into species-specific clusters with low sequence divergence between strains belonging to the same species (0 to 2%). The ITS-based tree topology only partially correlated to that based on 16S rDNA, but the main branching orders were preserved, notably, the division of fast-growing from slowly growing mycobacteria, separate branching for M. simiae, M. genavense, and M. triplex, and distinct branches for M. xenopi and M. shimoidei. Comparisons of M. gastri with M. kansasii and M. malmoense with M. szulgai revealed ITS sequence similarities of 93 and 88%, respectively. M. marinum and M. ulcerans possessed identical ITS sequences. Our results show that ITS sequencing represents a supplement to 16S rRNA gene sequences for the differentiation of closely related species. Slowly growing mycobacteria show a high sequence variation in the ITS; this variation has the potential to be used for the development of probes as a rapid approach to mycobacterial identification. PMID:9431937

  12. Progressive supranuclear palsy

    MedlinePlus

    Dementia-nuchal dystonia; Richardson-Steele-Olszewski syndrome; Palsy - progressive supranuclear ... Progressive supranuclear palsy is a condition that causes symptoms similar to those of Parkinson disease . It involves damage to many cells ...

  13. Progressive Pigmentary Purpura

    MedlinePlus

    ... Category: Share: Yes No, Keep Private Progressive Pigmentary Purpura Share | Progressive pigmentary purpura (we will call it PPP) is a group ... conditions ( Schamberg's disease , Lichenoid dermatitis of Gourgerot-Blum, purpura annularis telangiectodes of Majocchi and Lichen aureus). Schamberg's ...

  14. Model of slowly evolving flare.

    NASA Astrophysics Data System (ADS)

    Chiuderi Drago, F.; Landini, M.; Monsignori Fossi, B. C.

    A gradual rise and fall flare with a duration of about one hour was observed on June 10, 1980 in the radio (Toyokawa and VLA), optical (Bing Bear) and XUV (SMM satellite) ranges of wavelengths. The flare developed as a large loop connecting two regions of opposite polarity in a pre-existing active region. A model of the differential emission measure of the loop observed at three different stages of the flare is deduced from the analysis of the XUV images in C IV (1549 Å), O VIII (18.97 Å), Ne IX (13.45 Å), Mg XI (9.17 Å) and Si XIII (6.65 Å) emission lines. The differential emission measure as a function of temperature is controlled by the conductive flux via the temperature gradient; the evaluation of the divergence of the conductive flux is used in the energy balance to have information on the power deposition function.

  15. Synfuels from biomass grow slowly

    SciTech Connect

    Black, J.; Wedlock, J.C.

    1982-01-01

    Current developments in the manufacture of synfuels are discussed with emphasis on the sources of biomass suitable for synfuels production, processes for converting biomass to synfuels, and the economics of the technology. The sources include wood, nonwood crops, root crops, aquatic biomass, and oils from plants such as soybean, safflower, and peanut. The biomass conversion processes discussed include pyrolysis, gasification, liquefaction, and aerobic and anaerobic digestion.

  16. Slowly forgetting the Pavlovian adventure?

    PubMed

    Buser, Pierre

    2006-01-01

    This paper analyses an interesting story, that of the physiologist Ivan Petrovitch Pavlov. While investigating the causes of salivary secretions in the waking, behaving dog, he discovered a class of causes that he called psychic, since they were associated with perceiving a visual, acoustic or other signal, delivered before food that normally created salivation. A temporary relationship was therefore established, between the secretory command and the cerebral site associated with an initially neutral stimulus that had become a signal. This gave rise to the "conditional reflex". Pavlov was probably not the first who had observed this kind of association, but he very skillfully exploited these data to create a coherent conceptual system. In 23 "lectures", he very precisely summarized his views and retraced the fundamental issues explaining the main features of the purely physiological cerebral command of behaviour. The Pavlovian system necessarily became, in the particular environment of the soviet regime, a kind of credo on physical-mental relationships based upon a generalized reflexology, not allowing any deviation, nor any dissidence, nor any concession to subjectivity. The notion of conditional reflex has indeed resisted to time, but number of subtleties of the Pavlovian thinking and many phenomena that he described now seem forgotten and to have lost much of their heuristic value. Most of the recent theories of learning have only rarely followed Pavlov's line, to concentrate on more complex learning modalities. PMID:16731497

  17. Changes do happen - but slowly.

    PubMed

    2016-08-17

    Mike Paynter's career began in emergency departments in London, dealing with issues such as the King's Cross fire in the 1980s. He is now in Somerset, where he is a consultant nurse for community urgent care. PMID:27533413

  18. Disease progression in a patient with nonalcoholic steatohepatitis.

    PubMed

    Tseng, Ping-Huei; Liu, Chun-Jen; Kao, Jia-Horng; Shun, Chia-Tung; Chen, Pei-Jer; Chen, Ding-Shinn

    2008-10-01

    Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD). The prevalence and clinical significance of NAFLD/NASH have been increasingly recognized in Western countries but much less known in Asian countries, including Taiwan. Here, we report the case of a 43-year-old man who had abnormal liver tests for 18 years. Retrospective evaluation of his initial clinical, laboratory and histologic findings indicated that the hepatic disorder was compatible with the diagnosis of NASH. Although his liver biochemical tests improved after taking lipid-lowering agents, a liver biopsy 17 years later demonstrated histologic progression of intralobular necroinflammation and perivenular fibrosis. These facts suggest that NASH, albeit mild and slowly progressive, indeed exists in Taiwan. After the control of chronic hepatitis B and C and westernization of the lifestyle in Taiwan, an increasing burden of NAFLD/NASH is anticipated and active prophylactic measures should be implemented. PMID:18926950

  19. Secondary Student Progress Plan.

    ERIC Educational Resources Information Center

    District of Columbia Public Schools, Washington, DC.

    The Secondary Student Progress Plan aims to provide uniform educational expectations for successful course completion and progress toward graduation beginning with grade 7 in school year 1984-85. Arranged in outline form, the plan shows the course of study for grades 7-12, guidelines for evaluating and reporting student progress, promotion…

  20. Reconstructing Progressive Education

    ERIC Educational Resources Information Center

    Kaplan, Andy

    2013-01-01

    The work of Colonel Francis W. Parker, the man whom Dewey called "the father of progressive education," provides a starting point for reconstructing the loose ambiguities of progressive education into a coherent social and educational philosophy. Although progressives have claimed their approach is more humane and sensitive to children, we need…

  1. Spinal and bulbar muscular atrophy and Charcot-Marie-Tooth type 1A: Co-existence of two rare neuromuscular genetic diseases in the same patient.

    PubMed

    Sagnelli, Anna; Scaioli, Vidmer; Piscosquito, Giuseppe; Salsano, Ettore; Dalla Bella, Eleonora; Gellera, Cinzia; Pareyson, Davide

    2015-10-01

    Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by a trinucleotide CAG repeat expansion in the androgen receptor gene; it is clinically characterized by adult-onset, slowly progressive weakness and atrophy mainly affecting proximal limb and bulbar muscles. Charcot-Marie-Tooth disease type 1A is an autosomal dominant polyneuropathy due to peripheral myelin protein 22 gene duplication and characterized by slowly progressive distal limb muscle weakness, atrophy and sensory loss with foot deformities. Here we report the co-occurrence of both neuromuscular genetic diseases in the same male patient. Difficulties in climbing stairs and jaw weakness were presenting symptoms consistent with SBMA. However, predominant distal weakness and bilateral pes cavus were rather suggestive of a hereditary polyneuropathy. The combination of two diseases, even if extremely rare, should be considered in the presence of atypical symptoms; in the case of genetic diseases this event may have important implications on family members' counseling. PMID:26298608

  2. [A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

    PubMed

    Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka

    2003-01-01

    -meal hyperglycemia of Type 2 diabetes. Epalrestat (Ono Yakuhin Co., 1992) is effective for diabetic neuropathy by reducing the formation of sorbitol. These anti-DM drugs were recently studied and developed in Japan. 4) The Japan Diabetes Society proposed a guideline on diagnostic criteria and treatment of diabetes mellitus (DM) in 1999 and revised it in 2002. DM is classified as insulin-dependent DM (Type l) and non-insulin dependent DM (Type 2). Type 1, juvenile onset DM, requires insulin therapy to prevent ketosis and to sustain life. Treatment of type 2, adult onset DM, is recommended as a step-by-step method, starting with dietary-exercise therapy, followed by oral hypoglycemic drugs and then insulin therapy. DM patients with complications should have a therapy devised to match their circumstances. 5) Epidemiological aspects: The mortality rate of DM compared to the time of drug appearance was traced from 1920 to 2000. The curve goes down slowly in the time frame of World War II, but rises from 1950 to 1970. The elevation could not be suppressed by the appearance of SUs, BGs or improved insulin preparations. The curve runs flat from 1980 to 1990, which might be related to the use of purified insulin or human insulin therapy. The mortality rate of DM indicates that death by hyperglycemic coma and other deaths resulting from complications are excluded. The survey of the principal cause of death by DM during the period of 1981-1990 indicates that the death rate due to hyperglycemic coma is only 1.7% of the total deaths caused by DM. The effect of drug therapy on all of the death resulting from DM is not detected. Hospital visitation and admission rates of the DM patients have been recorded since 1952 in Japan. This curve is rising continuously, and none of the antidiabetic drugs has been able to suppress it. These data show that the antidiabetic drugs relieve DM symptoms through their effective hypoglycemic actions, but that they cannot suppress the mortality rate of DM. It is

  3. Progression of motor and nonmotor features of Parkinson's disease and their response to treatment

    PubMed Central

    Vu, Thuy C.; Nutt, John G.; Holford, Nicholas H. G.

    2012-01-01

    AIMS (i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments. METHODS Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters. RESULTS Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2–3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED50 of 1237 mg day−1 compared with 7–24 mg day−1 for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression. CONCLUSIONS This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD. PMID:22283961

  4. A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells.

    PubMed

    Huttunen, Kristiina M; Gynther, Mikko; Huttunen, Johanna; Puris, Elena; Spicer, Julie A; Denny, William A

    2016-06-23

    The l-type amino acid transporter 1 (LAT1) is a transmembrane protein carrying bulky and neutral amino acids into cells. LAT1 is overexpressed in several types of tumors, and its inhibition can result in reduced cancer cell growth. However, known LAT1 inhibitors lack selectivity over other transporters. In the present study, we designed and synthesized a novel selective LAT1 inhibitor (1), which inhibited the uptake of LAT1 substrate, l-leucin as well as cell growth. It also significantly potentiated the efficacy of bestatin and cisplatin even at low concentrations (25 μM). Inhibition was slowly reversible, as the inhibitor was able to be detached from the cell surface and blood-brain barrier. Moreover, the inhibitor was metabolically stable and selective toward LAT1. Since the inhibitor was readily accumulated into the prostate after intraperitoneal injection to the healthy mice, this compound may be a promising agent or adjuvant especially for the treatment of prostate cancer. PMID:27253989

  5. New slowly pulsating B stars in the field of the young open cluster NGC 2244 discovered by the MOST photometric satellite

    NASA Astrophysics Data System (ADS)

    Gruber, D.; Saio, H.; Kuschnig, R.; Fossati, L.; Handler, G.; Zwintz, K.; Weiss, W. W.; Matthews, J. M.; Guenther, D. B.; Moffat, A. F. J.; Rucinski, S. M.; Sasselov, D.

    2012-02-01

    During two weeks of nearly continuous optical photometry of the young open cluster NGC 2244 obtained by the Microvariability and Oscillations of STars (MOST) satellite, we discovered two new slowly pulsating B (SPB) stars, GSC 00154-00785 and GSC 00154-01871. We present frequency analyses of the MOST light curves of these stars, which reveal two oscillation frequencies (0.61 and 0.71 cycle d-1) in GSC 00154-00785 and two (0.40 and 0.51 cycle d-1) in GSC 00154-01871. These frequency ranges are consistent with g modes of ℓ≤ 2 excited in models of main-sequence or pre-main-sequence (PMS) stars of masses 4.5-5 M⊙ and solar composition (X, Z) = (0.7, 0.02). Published proper motion measurements and radial velocities are insufficient to establish unambiguously cluster membership for these two stars. However, the PMS models which fit best their eigenspectra have ages consistent with NGC 2244. If cluster membership can be confirmed, these would be the first known PMS SPB stars, and would open a new window on testing asteroseismically the interior structures of PMS stars. Based on data from MOST, a Canadian Space Agency mission operated by Microsat Systems Canada Inc. (formerly the space division of Dynacon, Inc.) and the University of Toronto Institute for Aerospace Studies and the University of British Columbia, with the assistance of the University of Vienna.

  6. Microstructural and drug release properties of oven-dried and of slowly or fast frozen freeze-dried MCC-Carbopol pellets.

    PubMed

    Gómez-Carracedo, Ana; Souto, Consuelo; Martínez-Pacheco, Ramón; Concheiro, Angel; Gómez-Amoza, José Luis

    2007-08-01

    The influence of the procedure and conditions of drying (oven-drying and freeze-drying after slow or fast freezing) and of the CaCl(2) concentration in the wetting liquid on the physical characteristics and drug release behaviour of microcrystalline cellulose (MCC)-carbopol 40:60 pellets containing theophylline or ketoprofen has been evaluated. The microstructural, morphological and mechanical properties can be modulated, to a large extent, through the control of the drying step and the CaCl(2) proportion. The drying step determines the volumetric contraction of the pellets and, consequently, the porosity parameters. When freeze-drying is applied, the freezing conditions have a marked influence on total porosity and mean pore size of the pellets. Slowly frozen pellets present the lowest porosity but the pores are the greatest. Pore size appears as a critical factor for achieving controlled release; the greater the pores, the faster the entrance of water and, consequently, the drug release. Therefore, if freeze-drying is used to remove water from wet pellets, the control of the ice formation is essential to modulate the release profiles. The practical possibilities of such modulation are especially clear for a slightly-water soluble drug, such as ketoprofen. PMID:17317125

  7. Three-dimensional imaging of progressive facial hemiatrophy (Parry-Romberg syndrome) with unusual conjunctival findings

    PubMed Central

    Gogineni, Subhas Babu; Shetty, Shishir Ram; D'souza, Deepa

    2011-01-01

    Progressive hemifacial atrophy, also known as Parry-Romberg syndrome, is an uncommon degenerative condition which is poorly defined. It is characterized by a slow and progressive atrophy affecting one side of the face. The onset usually occurs during the first two decades of life. Characteristically, the atrophy progresses slowly for several years, and then it becomes stable. Ophthalmic involvement is common, with progressive enophthalmos which is a frequent finding. Cutaneous pigmentation is common in such conditions, however its extension to the conjunctiva is rarely reported. We report a case of Parry Romberg syndrome with characteristic clinical and radiographic presentation accompanied with rare ocular findings. The clinical features, radiological findings, and differential diagnoses to be considered, and the available treatment options are discussed in this report. PMID:22232729

  8. Tight asteroseismic constraints on core overshooting and diffusive mixing in the slowly rotating pulsating B8.3V star KIC 10526294

    NASA Astrophysics Data System (ADS)

    Moravveji, E.; Aerts, C.; Pápics, P. I.; Triana, S. A.; Vandoren, B.

    2015-08-01

    Context. KIC 10526294 was recently discovered to be a very slowly rotating and slowly pulsating late B-type star. Its 19 consecutive dipole gravity modes constitute a series with almost constant period spacing. This unique collection of identified modes probes the near-core environment of this star and holds the potential to reveal the size and structure of the overshooting zone above the convective core, as well as the mixing properties of the star. Aims: We revisit the asteroseismic modelling of this star with specific emphasis on the properties of the core overshooting, while considering additional diffusive mixing throughout the radiative envelope of the star. Methods: We pursued forward seismic modelling based on adiabatic eigenfrequencies of equilibrium models for eight extensive evolutionary grids tuned to KIC 10526294 by varying the initial mass, metallicity, chemical mixture, and the extent of the overshooting layer on top of the convective core. We examined models for both OP and OPAL opacities and tested the occurrence of extra diffusive mixing throughout the radiative interior. Results: We find a tight mass-metallicity relation within the ranges M ∈ [ 3.13,3.25 ] M⊙ and Z ∈ [ 0.014,0.028 ]. We deduce that an exponentially decaying diffusive core overshooting prescription describes the seismic data better than a step function formulation and derive a value of fov between 0.017 and 0.018. Moreover, the inclusion of extra diffusive mixing with a value of log Dmix between 1.75 and 2.00 dex (with Dmix in cm2 s-1) improves the goodness-of-fit based on the observed and modelled frequencies by a factor ~11 compared to the case where no extra mixing is considered, irrespective of the (M,Z) combination within the allowed seismic range. Conclusions: The inclusion of diffusive mixing in addition to core overshooting is essential to explain the structure in the observed period spacing pattern of this star. Moreover, for the input physics and chemical mixtures

  9. Fos Protein Expression in Olfactory-Related Brain Areas after Learning and after Reactivation of a Slowly Acquired Olfactory Discrimination Task in the Rat

    ERIC Educational Resources Information Center

    Roullet, Florence; Lienard, Fabienne; Datiche, Frederique; Cattarelli, Martine

    2005-01-01

    Fos protein immunodetection was used to investigate the neuronal activation elicited in some olfactory-related areas after either learning of an olfactory discrimination task or its reactivation 10 d later. Trained rats (T) progressively acquired the association between one odor of a pair and water-reward in a four-arm maze. Two groups of…

  10. THE CANCER PROGRESS REPORT

    EPA Science Inventory

    The Cancer Progress Report 2001 is about our Nation's progress against cancer. The information was gathered through a collaborative effort with other key agencies and groups, such as the Centers for Disease Control and Prevention and the American Cancer Society. Data on this site...

  11. Progression in Measuring.

    ERIC Educational Resources Information Center

    Brown, Margaret; And Others

    1995-01-01

    Describes a study by British researchers that attempted to describe progression in learning in terms of a common framework for all students. Elementary school students completed periodic interviews while being taught measurement skills. Results found a wide spread of attainment in measurement in each age range but less clear progression between…

  12. Complementary processing of haptic information by slowly and rapidly adapting neurons in the trigeminothalamic pathway. Electrophysiology, mathematical modeling and simulations of vibrissae-related neurons

    PubMed Central

    Sanchez-Jimenez, Abel; Torets, Carlos; Panetsos, Fivos

    2013-01-01

    Tonic (slowly adapting) and phasic (rapidly adapting) primary afferents convey complementary aspects of haptic information to the central nervous system: object location and texture the former, shape the latter. Tonic and phasic neural responses are also recorded in all relay stations of the somatosensory pathway, yet it is unknown their role in both, information processing and information transmission to the cortex: we don't know if tonic and phasic neurons process complementary aspects of haptic information and/or if these two types constitute two separate channels that convey complementary aspects of tactile information to the cortex. Here we propose to elucidate these two questions in the fast trigeminal pathway of the rat (PrV-VPM: principal trigeminal nucleus-ventroposteromedial thalamic nucleus). We analyze early and global behavior, latencies and stability of the responses of individual cells in PrV and medial lemniscus under 1–40 Hz stimulation of the whiskers in control and decorticated animals and we use stochastic spiking models and extensive simulations. Our results strongly suggest that in the first relay station of the somatosensory system (PrV): (1) tonic and phasic neurons process complementary aspects of whisker-related tactile information (2) tonic and phasic responses are not originated from two different types of neurons (3) the two responses are generated by the differential action of the somatosensory cortex on a unique type of PrV cell (4) tonic and phasic neurons do not belong to two different channels for the transmission of tactile information to the thalamus (5) trigeminothalamic transmission is exclusively performed by tonically firing neurons and (6) all aspects of haptic information are coded into low-pass, band-pass, and high-pass filtering profiles of tonically firing neurons. Our results are important for both, basic research on neural circuits and information processing, and development of sensory neuroprostheses. PMID:23761732

  13. A storm modeling system as an advanced tool in prediction of well organized slowly moving convective cloud system and early warning of severe weather risk

    NASA Astrophysics Data System (ADS)

    Spiridonov, Vlado; Curic, Mladjen

    2015-02-01

    Short-range prediction of precipitation is a critical input to flood prediction and hence the accuracy of flood warnings. Since most of the intensive processes come from convective clouds-the primary aim is to forecast these small-scale atmospheric processes. One characteristic pattern of organized group of convective clouds consist of a line of deep convection resulted in the repeated passage of heavy-rain-producing convective cells over NW part of Macedonia along the line. This slowly moving convective system produced extreme local rainfall and hailfall in urban Skopje city. A 3-d cloud model is used to simulate the main storm characteristic (e.g., structure, intensity, evolution) and the main physical processes responsible for initiation of heavy rainfall and hailfall. The model showed a good performance in producing significantly more realistic and spatially accurate forecasts of convective rainfall event than is possible with current operational system. The output results give a good initial input for developing appropriate tools such as flooding indices and potential risk mapping for interpreting and presenting the predictions so that they enhance operational flood prediction capabilities and warnings of severe weather risk of weather services. Convective scale model-even for a single case used has proved significant benefits in several aspects (initiation of convection, storm structure and evolution and precipitation). The storm-scale model (grid spacing-1 km) is capable of producing significantly more realistic and spatially accurate forecasts of convective rainfall events than is possible with current operational systems based on model with grid spacing 15 km.

  14. (U-Th-Sm)/He thermochronological age distribution in a slowly cooled plutonic complex (Ploumanac'h intrusion, France): insights into helium diffusion processes.

    NASA Astrophysics Data System (ADS)

    Recanati, A. C.; Gautheron, C.; Barbarand, J.; Tassan-Got, L.; Missenard, Y.; Pinna-Jamme, R.

    2015-12-01

    (U-Th-Sm)/He thermochronology is widely used to determine the thermal histories of mountain ranges and sedimentary basins. Apatite crystals retain helium at low temperatures, thus giving an insight into upper crustal evolution (e.g. exhumation, subsidence, erosion). Advanced models predict He production and diffusion rates in apatite crystals, thereby allowing determination of helium dates by integration over time/temperature paths (e.g. Gautheron et al., 2009). However, scattered dates and discordance between predicted and measured dates suggest that other parameters than time or temperature may also influence helium contents in apatite. The present study determines the variables that affect He diffusion in apatite over long timescales. We report the (U-Th-Sm)/He date distribution within a slowly cooled intrusion, along with AFT data, as well as extensive petrological and chemical characterization. The Ploumanac'h site (Brittany, France) was chosen because it includes small-scale spatial variations in petrology and chemistry (6-9106 tracks/cm2). GAUTHERON C., TASSAN-GOT L., BARBARAND J., PAGEL M., 2009. Effect of alpha-damage annealing on apatite (U-Th)/He thermochronology. Chem. Geol. 266, 166-179.

  15. Investigation of Very Slowly Tumbling Spin Labels by Nonlinear Spin Response Techniques: Theory and Experiment for Stationary Electron Electron Double Resonance

    PubMed Central

    Smigel, Murray D.; Dalton, Larry R.; Hyde, James S.; Dalton, Lauraine A.

    1974-01-01

    The investigation of very slowly tumbling spin labels by nonlinear electron spin response techniques is discussed. Such techniques permit characterization of rotational processes with correlation times from 10-3 to 10-7 sec even though the linear spin response (ESR) technique is insensitive to motion in this region. Nonlinear techniques fall into two categories: (a) Techniques (referred to as passage techniques) in which the distribution of saturation throughout the spin system is determined both by the applied magnetic field modulation of the resonance condition and by the modulation of the resonance frequency induced by the molecular motion. The time dependence of this distribution produces phase and amplitude changes in the observed signals. (b) Techniques that measure the integral of the distribution function of the time required for saturated spin packets to move between pumped and observed portions of the spectrum [stationary and pulsed electron electron double resonance (ELDOR) techniques]. Quantitative analysis of passage ESR and stationary ELDOR techniques can be accomplished employing a density matrix treatment that explicitly includes the interaction of the spins with applied radiation and modulation fields. The effect of molecular motion inducing a random modulation of the anisotropic spin interactions can be calculated by describing the motion by the diffusion equation appropriate to the motional model assumed. For infinitesimal steps the eigen-functions of the diffusion operator are known analytically, while for random motion of arbitrary step size they are determined by diagonalizing the transition matrix appropriate for the step model used. The present communication reports investigation of the rotational diffusion of the spin label probes 2,2,6,6-tetramethyl-4-piperidinol-1-oxyl and 17β-hydroxy-4′,4′-dimethylspiro-[5α-androstane-3,2′-oxazolidin]-3′-oxyl in sec-butylbenzene. Experimental spectra are compared with computer simulations of

  16. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.; Shu, Huidy; Haman, Aissa; Sejvar, James J.; Miller, Bruce L.

    2009-01-01

    In contrast with more common dementing conditions that typically develop over years, rapidly progressive dementias can develop subacutely over months, weeks, or even days and be quickly fatal. Because many rapidly progressive dementias are treatable, it is paramount to evaluate and diagnose these patients quickly. This review summarizes recent advances in the understanding of the major categories of RPD and outlines efficient approaches to the diagnosis of the various neurodegenerative, toxic-metabolic, infectious, autoimmune, neoplastic, and other conditions that may progress rapidly. PMID:18668637

  17. Increasing psychotherapists' adoption and implementation of the evidence-based practice of progress monitoring.

    PubMed

    Persons, Jacqueline B; Koerner, Kelly; Eidelman, Polina; Thomas, Cannon; Liu, Howard

    2016-01-01

    Evidence-based practices (EBPs) reach consumers slowly because practitioners are slow to adopt and implement them. We hypothesized that giving psychotherapists a tool + training intervention that was designed to help the therapist integrate the EBP of progress monitoring into his or her usual way of working would be associated with adoption and sustained implementation of the particular progress monitoring tool we trained them to use (the Depression Anxiety Stress Scales on our Online Progress Tracking tool) and would generalize to all types of progress monitoring measures. To test these hypotheses, we developed an online progress monitoring tool and a course that trained psychotherapists to use it, and we assessed progress monitoring behavior in 26 psychotherapists before, during, immediately after, and 12 months after they received the tool and training. Immediately after receiving the tool + training intervention, participants showed statistically significant increases in use of the online tool and of all types of progress monitoring measures. Twelve months later, participants showed sustained use of any type of progress monitoring measure but not the online tool. PMID:26618237

  18. Aluminum involvement in the progression of Alzheimer's disease.

    PubMed

    Walton, J R

    2013-01-01

    The neuroanatomic specificity with which Alzheimer's disease (AD) progresses could provide clues to AD etiopathology. Magnetic resonance imaging studies of AD clinical progression have confirmed general conclusions from earlier studies of AD neuropathological progression wherein neurofibrillary tangle pathology was observed to spread along a well-defined sequence of corticocortical and corticosubcortical connections, preferentially affecting certain cell types, while sparing others. Identical and non-identical twin studies have consistently shown AD has mixed (environmental and genetic) etiopathogenesis. The decades-long prodromal phase over which AD develops suggests slow but progressive accumulation of a toxic or infective agent over time. Major environmental candidates are reviewed to assess which best fits the profile of an agent that slowly accrues in susceptible cell types of AD-vulnerable brain regions to toxic levels by old age, giving rise to AD neuropathology without rapid neuronal lysis. Chronic aluminum neurotoxicity best matches this profile. Many humans routinely ingest aluminum salts as additives contained in processed foods and alum-treated drinking water. The physical properties of aluminum and ferric iron ions are similar, allowing aluminum to use mechanisms evolved for iron to enter vulnerable neurons involved in AD progression, accumulate in those neurons, and cause neurofibrillary damage. The genetic component of AD etiopathogenesis apparently involves a susceptibility gene, yet to be identified, that increases aluminum absorption because AD and Down syndrome patients have higher than normal plasma, and brain, aluminum levels. This review describes evidence for aluminum involvement in AD neuropathology and the clinical progression of sporadic AD. PMID:23380995

  19. Slowly relaxing local structure (SRLS) analysis of 15N-H relaxation from the prototypical small proteins GB1 and GB3.

    PubMed

    Shapiro, Yury E; Meirovitch, Eva

    2012-04-01

    15N-H relaxation parameters from the first (GB1) and third (GB3) immunoglobulin-binding domains of streptococcal protein G were analyzed previously with the traditional model-free (MF) method. These proteins comprise an α-helix and a four-stranded β-sheet. An extensive study of GB1 (GB3) used combined three-field (five-field) data acquired in the 278-323 K range (at 297 K). For successful analysis of the GB3 data, it was necessary to allow for variations in the 15N chemical shift anisotropy (CSA) tensor and virtually eliminate the local motion. In the case of GB1, the spectral density was parametrized. Here, we analyze these data with the slowly relaxing local structure (SRLS) approach, which is the generalization of MF in allowing for general tensorial properties, and accounting for mode-coupling. A standard (featuring constant magnetic tensors) SRLS fitting scheme is used. This analysis accounts for the important asymmetry of the local spatial restrictions; it provides physical order parameters, local diffusion rates, related activation energies, and key features of local geometry. Using data from GB3 we show that the main local ordering axis is C(i-1)(α) - C(i)(α), and the average axial (rhombic) order parameter is -0.457 ± 0.017 (1.156 ± 0.015) for the α-helix and -0.484 ± 0.002 (1.10 ± 0.04) for the rest of the polypeptide chain. The N-H bonds within (outside of) the α-helix reorient locally with an average correlation time, (τ), of 310 (130) ps, as compared to 3.33 ns for the global tumbling. Several N-H bonds in the loops β1/β2, β2/α-helix, and α-helix/β3 have (τ) of 380, 320, and 750 ps, respectively. The distinctive experimental data of the α-helix are due to relatively weak and substantially rhombic local ordering and slow local motion. For GB1, we derive activation energies from local diffusion rates. They are 43.3 ± 7.1 kJ/mol for the β-strands, 24.7 ± 3.9 kJ/mol for the α-helix (and approximately for the loop β3/β4), and 18.9

  20. Properties of Slowly Moving Thermal Waves in Saturn from Cassini CIRS and Ground-Based Thermal Observations from 2003 to 2009

    NASA Astrophysics Data System (ADS)

    Orton, Glenn S.; Fletcher, L. N.; Flasar, F.; Achterberg, R. K.; Yanamandra-Fisher, P. A.; Lewis, M.; Fujiyoshi, T.; Bell, J.; Christian, J.; Brown, S. K.

    2013-10-01

    Hemispherical maps of Saturn’s atmosphere made both by Cassini’s Composite Infrared Spectrometer (CIRS, 7-1000 µm) and ground-based mid-infrared observations (7-25 µm) were surveyed for the presence and properties of zonal thermal waves and their variability in time. The most inclusive CIRS surveys, FIRMAPs (15 cm-1 spectral resolution), covered the planet from the equator to either north or south pole, sweeping through the latitude range while the planet rotated beneath over its ~10-hour rotation. Ground-based observations were made at the Infrared Telescope Facility using the MIRSI instrument, the Very Large Telescope using VISIR and the Subaru Telescope using COMICS. We sampled spectral ranges dominated both by upper-tropospheric emission (80-200 mbar) and by stratospheric emission (0.5-3 mbar). We examined data that were taken between 2003 and Saturn’s spring equinox in 2009. During this time, the strongest waves were found between planetographic latitudes of 30° - 45°S and 0° - 30°N. Some low-wavelength components cover all 360° in longitude, similar to the slowly moving thermal waves in Jupiter’s atmosphere, but the strongest waves were found in “trains” that covered less than 180°. In 2005, tropospheric waves had a mean peak-to-peak variance that was the equivalent of temperature variability of about 1 K. Between 2005 and 2007, they had subsided to about 0.5 K. During and after 2008, they soared to over 3 K. During this entire period, similar waves in the northern hemisphere were never larger than 0.8 K. In the stratosphere, waves followed a similar time sequence, with southern hemisphere waves in 2005 reaching amplitudes as high as 3.5 K in brightness temperature, subsequently decreasing, then growing in 2008-2009 to over 5 K. Stratospheric waves in the northern hemisphere were nearly constant ~2 K, but with an instance of 6 K at one epoch in 2008. We were able to track the phase of some of the waves in the southern hemisphere, which

  1. Deep-seated slowly moving rock slides in foliated metamorphic rock masses: New findings about kinematical and hydro-mechanical processes

    NASA Astrophysics Data System (ADS)

    Zangerl, Christian; Strauhal, Thomas; Holzmann, Michael

    2013-04-01

    Deep-seated slowly moving rock slides are characterised by deformation along one or several shear zones where most of the measured total slope displacement localizes. Many of these rock slides move downwards at mean annual rates of some centimetres or even less and do not show any evidence for non-reversible acceleration in the past or in the future. Whereas some of these rock slides are currently inactive (dormant) or have even reached a stabilised final state others show a temporally variable deformation behaviour characterized by low base activities superimposed by acceleration phases. The trigger for these phases can be manifold and include heavy rainfall, snow melt, water level fluctuations of reservoirs, changes in the slope's equilibrium state due to antecedent slow creeping processes, variations in the material behaviour within the shear/sliding zone, erosion along the foot of the slope, etc. In order to improve the understanding of the activity behaviour and trigger factors, to increase the quality of slope stability analyses and to assess the hazard potential detailed information about the rock slide geometry and kinematics are essential. Given that subsurface investigations such as boreholes and investigation adits on large-scale rock slides are costly, most published studies are related to investigations in the surroundings of infrastructures and human settlements. Within this study new field mapping, deformation monitoring, geophysical exploration and in-situ subsurface investigation data are presented which are obtained on case studies in paragneissic rock masses of the Austroalpine Ötztal-Stubai complex (Tyrol, Austria). The new investigations contribute to develop geometrical rock slide models, to study the internal deformation characteristics of the rock slide mass and to develop kinematical deformation models. In addition, results show that all case studies are characterised by slope deformation mechanisms due to shear/slide processes along dm to

  2. Progress toward seasonal prediction in the tropics

    NASA Astrophysics Data System (ADS)

    Knaff, John Albert

    Seasonal prediction in the tropics has been a slowly developing, yet very important topic in Atmospheric Science. Its slow evolution is a product of its history, a history determined by the rise and fall of empires, technological advances, and scientific opinions, but motivated ultimately by profit. In recent years, long-lead forecasting techniques in the tropics have again become popular. The occurrence of strong El Nino/Southern Oscillation (ENSO) events, droughts, floods, and intense landfalling tropical cyclones, has again prompted the meteorological community to use their knowledge to create useful seasonal forecasts for several regions of the tropics. Such forecasts will facilitate better management of natural resources, disaster preparation, and economic growth in these regions. Much has been learned about seasonal forecasting in the tropics in the last 125 years and much will be learned in the future, but progress is gained slowly by the piecing together of a great number of observation studies. This paper details but a few such studies. Within, the history of seasonal prediction in the tropics is discussed. Following this discussion the paper examines the physical implications of summertime sea level pressure anomalies (SLPAs) in the tropical Atlantic, the development of a simple regression model to predict June through September SLPAs in the Caribbean Sea region, and the development of a statistical ENSO prediction method which is based entirely on the optimal combination of persistence, trends of initial conditions and climatology. The future of seasonal forecasting in the tropics is bright. New technology along with improved datasets is allowing diagnostic and predictive studies that were once thought too exhaustive to be undertaken. This optimistic opinion must be tempered by this fields long history. Public and scientific opinion can rapidly change if seasonal prediction is not approached responsibly. This responsibility entails a rigorous definition

  3. Progress for the Paralyzed

    MedlinePlus

    ... this page please turn Javascript on. Feature: NIBIB Robotics Progress for the Paralyzed Past Issues / Spring 2013 ... Paralyzed —The expanding options for paralyzed individuals include: robotic arms spinal cord stimulation improved prosthetic limbs restored ...

  4. Progress and promise.

    PubMed

    Kamphaus, Randy W

    2012-12-01

    This editorial introduces the current issue of the journal School Psychology Quarterly (SPQ).There has been an impressive and promising progress of school psychology science has been reflected in every issue of SPQ, including the current one. PMID:23294232

  5. Orion Progress - Spring 2010

    NASA Video Gallery

    NASA and contractor teams are designing, building and testing the next generation human spacecraft Orion. Progress on Orion is highlighted by employees working on the project, along with video of t...

  6. CHEMICALS IN PROGRESS BULLETIN

    EPA Science Inventory

    Chemicals in Progress Bulletin is a quarterly newsletter which highlights regulatory and program activities of the Office of Pollution Prevention and Toxics. Regular features and news items include the existing chemicals program, new chemicals program, pollution prevention activi...

  7. A size threshold governs Caenorhabditis elegans developmental progression.

    PubMed

    Uppaluri, Sravanti; Brangwynne, Clifford P

    2015-08-22

    The growth of organisms from humans to bacteria is affected by environmental conditions. However, mechanisms governing growth and size control are not well understood, particularly in the context of changes in food availability in developing multicellular organisms. Here, we use a novel microfluidic platform to study the impact of diet on the growth and development of the nematode Caenorhabditis elegans. This device allows us to observe individual worms throughout larval development, quantify their growth as well as pinpoint the moulting transitions marking successive developmental stages. Under conditions of low food availability, worms grow very slowly, but do not moult until they have achieved a threshold size. The time spent in larval stages can be extended by over an order of magnitude, in agreement with a simple threshold size model. Thus, a critical worm size appears to trigger developmental progression, and may contribute to prolonged lifespan under dietary restriction. PMID:26290076

  8. Differential motor neuron involvement in progressive muscular atrophy: a comparative study with amyotrophic lateral sclerosis

    PubMed Central

    Riku, Yuichi; Atsuta, Naoki; Yoshida, Mari; Tatsumi, Shinsui; Iwasaki, Yasushi; Mimuro, Maya; Watanabe, Hirohisa; Ito, Mizuki; Senda, Jo; Nakamura, Ryoichi; Koike, Haruki; Sobue, Gen

    2014-01-01

    Objective Progressive muscular atrophy (PMA) is a clinical diagnosis characterised by progressive lower motor neuron (LMN) symptoms/signs with sporadic adult onset. It is unclear whether PMA is simply a clinical phenotype of amyotrophic lateral sclerosis (ALS) in which upper motor neuron (UMN) signs are undetectable. To elucidate the clinicopathological features of patients with clinically diagnosed PMA, we studied consecutive autopsied cases. Design Retrospective, observational. Setting Autopsied patients. Participants We compared clinicopathological profiles of clinically diagnosed PMA and ALS using 107 consecutive autopsied patients. For clinical analysis, 14 and 103 patients were included in clinical PMA and ALS groups, respectively. For neuropathological evaluation, 13 patients with clinical PMA and 29 patients with clinical ALS were included. Primary outcome measures Clinical features, UMN and LMN degeneration, axonal density in the corticospinal tract (CST) and immunohistochemical profiles. Results Clinically, no significant difference between the prognosis of clinical PMA and ALS groups was shown. Neuropathologically, 84.6% of patients with clinical PMA displayed UMN and LMN degeneration. In the remaining 15.4% of patients with clinical PMA, neuropathological parameters that we defined as UMN degeneration were all negative or in the normal range. In contrast, all patients with clinical ALS displayed a combination of UMN and LMN system degeneration. CST axon densities were diverse in the clinical PMA group, ranging from low values to the normal range, but consistently lower in the clinical ALS group. Immunohistochemically, 85% of patients with clinical PMA displayed 43-kDa TAR DNA-binding protein (TDP-43) pathology, while 15% displayed fused-in-sarcoma (FUS)-positive basophilic inclusion bodies. All of the patients with clinical ALS displayed TDP-43 pathology. Conclusions PMA has three neuropathological background patterns. A combination of UMN and LMN

  9. The underrecognized progressive nature of N370S Gaucher disease and assessment of cancer risk in 403 patients

    PubMed Central

    Taddei, Tamar H.; Kacena, Katherine A.; Yang, Mei; Yang, Ruhua; Malhotra, Advitya; Boxer, Michael; Aleck, Kirk A.; Rennert, Gadi; Pastores, Gregory M.; Mistry, Pramod K.

    2010-01-01

    Mutations in GBA1 gene that encodes lysosomal glucocerebrosidase result in Type 1 Gaucher Disease (GD), the commonest lysosomal storage disorder; the most prevalent disease mutation is N370S. We investigated the heterogeneity and natural course of N370S GD in 403 patients. Demographic, clinical, and genetic characteristics of GD at presentation were examined in a cross-sectional study. In addition, the relative risk (RR) of cancer in patients compared with age-, sex-, and ethnic-group adjusted national rates of cancer was determined. Of the 403 patients, 54% of patients were homozygous (N370S/N370S) and 46% were compound heterozygous for the N370S mutation (N370S/other). The majority of N370S/N370S patients displayed a phenotype characterized by late onset, predominantly skeletal disease, whereas the majority of N370S/other patients displayed early onset, predominantly visceral/hematologic disease, P < 0.0001. There was a striking increase in lifetime risk of multiple myeloma in the entire cohort (RR 25, 95% CI 9.17–54.40), mostly confined to N370S homozygous patients. The risk of other hematologic malignancies (RR 3.45, 95% CI 1.49–6.79), and overall cancer risk (RR 1.80, 95% CI 1.32–2.40) was increased. Homozygous N370S GD leads to adult-onset progressive skeletal disease with relative sparing of the viscera, a strikingly high risk of multiple myeloma, and an increased risk of other cancers. High incidence of gammopathy suggests an important role of the adaptive immune system in the development of GD. Adult patients with GD should be monitored for skeletal disease and cancers including multiple myeloma. PMID:19260119

  10. Progressive cone dystrophies.

    PubMed

    François, J; De Rouck, A; De Laey, J J

    1976-01-01

    Patients with progressive generalized cone dystrophy often present nystagmus (or strabism) and complain of photophobia, decrease in visual acuity or disturbances in colour perception. The most classic fundus abnormality is the bull's eye maculopathy or a pallor of the optic disc. Minimal macular changes are sometimes seen, which may progress to a bull's eye type of macular degeneration. The photopic ERG is always very affected, whereas at first the scotopic ERG seems normal. Progressive deterioration of the visual functions is accompanied by increasing fundus lesions and rod involvement, as suggested by the modifications of the dark adaptation curve and the scotopic ERG. However, the progression of typical generalized cone dysfunction is very slow. On the contrary, in some cases of so-called Stargardt's disease with peripheral participation, a very rapid progression has been observed. In such cases a normal ERG does not necessarily mean that the disease will remain localized to the macular area. No definite prognosis can be made on one single ERG. In 3 cases with sector pigmentary retinopathy the photopic ERG was more affected than the scotopic ERG. However, these cases are probably primary cone-rod dystrophies. Although there is no electrophysiological control, our clinical impression is that the evolution, if possible, is very slow. PMID:1066593

  11. Progressive multiple sclerosis

    PubMed Central

    Ontaneda, Daniel; Fox, Robert J.

    2015-01-01

    Purpose to Review To highlight the pathological features and clinical aspects of progressive multiple sclerosis (PMS). To highlight results of clinical trial experience to date and review ongoing clinical trials and perspective new treatment options. Explain the challenges of clinical trial design in PMS. Recent Findings MS has been identified as a chronic immune mediated disease, and the progressive phase of the disease appears to have significant neurodegenerative mechanisms. The classification of the course of PMS has been re-organized into categories of active vs. inactive inflammatory disease and the presence vs. absence of gradual disease progression. This differentiation allows clearer conceptualization of PMS and possibly even more efficient recruitment of PMS subjects into clinical trials. Clinical trial experience to date in PMS has been negative with anti-inflammatory medications used in relapsing MS. Simvastatin was recently tested in a phase II trial and showed a 43% reduction on annualized atrophy progression in secondary progressive MS. Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod, and anti-B-cell therapy ocrelizumab. Several efforts for development of outcome measures in PMS are ongoing. Summary PMS represents a significant challenge, as the pathogenesis of the disease is not well understood, no validated outcome metrics have been established, and clinical trial experience to date has been disappointing. Advances in the understanding of the disease and lessons learned in previous clinical trials are paving the way for successful development of disease modifying agents for this disease. PMID:25887766

  12. The genetics of Leigh syndrome and its implications for clinical practice and risk management

    PubMed Central

    Ruhoy, Ilene S; Saneto, Russell P

    2014-01-01

    Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient’s family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms. PMID:25419155

  13. Progressive supranuclear palsy: progression and survival.

    PubMed

    Arena, Julieta E; Weigand, Stephen D; Whitwell, Jennifer L; Hassan, Anhar; Eggers, Scott D; Höglinger, Günter U; Litvan, Irene; Josephs, Keith A

    2016-02-01

    Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder characterized by postural instability and falls, vertical supranuclear gaze palsy, parkinsonism with poor levodopa response, pseudobulbar palsy, and frontal release signs. The natural history of the disease has been previously described. However, the time frame of appearance of clinical milestones and how these symptoms may relate to survival in PSP are unknown. The primary objective was to determine the prevalence of symptoms at different stages of PSP and to estimate the time of appearance of clinical symptoms characteristic of the disease. Second, we determined the association between clinical symptoms and survival. We prospectively studied 35 PSP patients during assessments scheduled every 6 months for up to 2 years. We estimated symptoms prevalence and the association between symptoms and survival. The median age of onset was 65.9 years (IQR 60.6-70.0), and the median time from onset to first assessment was 3.0 years (IQR 2.4-3.9). The most commonly reported symptoms at baseline were: motor (100%) followed by cognitive/behavioral (89%), systemic and bulbar (80%), and sleep disturbances (60%). Slowness of movement, falls, neck stiffness and difficulty looking up/down had high prevalence from baseline, while balance and gait impairment were less common at baseline but increased in prevalence over time. The presence of sleep disturbances, and possibly hallucinations, was associated with increased death risk. Improved recognition of the clinical spectrum and milestones of PSP advances knowledge of the disease, helps earlier diagnosis, and allows prognostic predictions. PMID:26705121

  14. Progressive External Ophthalmoplegia.

    PubMed

    McClelland, Collin; Manousakis, Georgios; Lee, Michael S

    2016-06-01

    Progressive external ophthalmoplegia (PEO), marked by progressive bilateral ptosis and diffuse reduction in ocular motility, represents a finding of mitochondrial myopathy rather than a true diagnosis. PEO often occurs with other systemic features of mitochondrial dysfunction that can cause significant morbidity and mortality. Accurate and early recognition of PEO is paramount for the optimal care of these patients. We present an evidence-based review of the presenting neuro-ophthalmic features, differential diagnosis, diagnostic tools, systemic implications, and treatment options for isolated PEO and other PEO-associated mitochondrial syndromes. PMID:27072953

  15. MCNP Progress & Performance Improvements

    SciTech Connect

    Brown, Forrest B.; Bull, Jeffrey S.; Rising, Michael Evan

    2015-04-14

    Twenty-eight slides give information about the work of the US DOE/NNSA Nuclear Criticality Safety Program on MCNP6 under the following headings: MCNP6.1.1 Release, with ENDF/B-VII.1; Verification/Validation; User Support & Training; Performance Improvements; and Work in Progress. Whisper methodology will be incorporated into the code, and run speed should be increased.

  16. MEASURING POLLUTION PREVENTION PROGRESS

    EPA Science Inventory

    The workshop, "Measuring Pollution Prevention Progress," was held in Salem, MA, March 31 - April 2, 1993. he purpose of this workshop was to present the latest significant research and practical findings related to pollution prevention measurement from ongoing and recently comple...

  17. [Progressive hearing loss].

    PubMed

    Reiss, M; Reiss, G

    2000-01-01

    Progressive sensorineural hearing loss (SNHL) is defined as hearing loss of unknown etiology with fairly high-speed progression. Its diagnostic criteria consist of the following: that it is 1) progressive, 2) with bilateral involvement, and 3) of unknown etiology. Due to recent advances in diagnostics, imaging and management, SNHL has gained much interest from otologists in the last few years. They provide new insight into the physiology and pathophysiology of hearing. SNHL which is sudden in onset, fluctuating, and/or progressive complicates medical management, hearing aid selection, and individualized educational planning for a hearing-impaired patient. Existing hypotheses on the etiology of SNHL are judged on experimental, clinical, laboratory and radiological evidence. Cardiovascular and rheologic diseases, hereditary disorders, immunological phenomena, infections, environmental causes like noise, ototoxic drugs and industrial substances and systemic maladies must be included in the diagnostic reflections. Potential concepts of treatment include rheologic medications and corticosteroids. Hearing aids and timely cochlear implant operation are further possible forms of treatment. PMID:10893764

  18. Progressive Myoclonus Epilepsies.

    PubMed

    Kälviäinen, Reetta

    2015-06-01

    The progressive myoclonus epilepsies (PMEs) comprise a group of rare and heterogeneous disorders defined by the combination of action myoclonus, epileptic seizures, and progressive neurologic deterioration. Neurologic deterioration may include progressive cognitive decline, ataxia, neuropathy, and myopathy. The gene defects for the most common forms of PME (Unverricht-Lundborg disease, Lafora disease, several forms of neuronal ceroid lipofuscinoses, myoclonus epilepsy with ragged-red fibers [MERRF], and type 1 and 2 sialidoses) have been identified. The prognosis of a PME depends on the specific disease. Lafora disease, the neuronal ceroid lipofuscinoses, and the neuronopathic form of Gaucher disease have an invariably fatal course. In contrast, Unverricht-Lundborg disease has a much slower progression, and with adequate care many patients have a normal life span. The specific diseases that cause PME are diagnosed by recognition of their age of onset, the associated clinical symptoms, the clinical course, the pattern of inheritance, and by special investigations such as enzyme measurement, skin/muscle biopsy, or gene testing. PMID:26060909

  19. Basic Measures of Progress.

    ERIC Educational Resources Information Center

    Calkins, Julia; Ling, Thomson; Moore, Eric; Halle, Tamara; Hair, Beth; Moore, Kris; Zaslow, Marty

    This document provides a compilation of measures of progress toward school readiness and three contributing conditions as used in several local, state, and national surveys. The report begins with a legend listing the surveys examined, their acronyms, and contact information. The remainder of the report, in tabular format, lists measures of…

  20. Mystery in Progress.

    ERIC Educational Resources Information Center

    Hall, Kristen

    1989-01-01

    Describes "Mystery in Progress," a traveling exhibit which traces the development of Predynastic Egypt. The exhibit provides a time line for Predynastic Egypt, depicts the history of the Hierakonpolis expedition, documents the formation of Egypt's first centralized nation state, and summarizes the emergence of a unified Egypt. (LS)

  1. 1992 PVUSA progress report

    SciTech Connect

    Ellyn, W.

    1992-12-31

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale photovoltaic (PV) electric generating systems. This report updates the progress of the PVUSA project, reviews the status and performance of the various PV installations during 1992, and summarizes key accomplishments and conclusions from work to date.

  2. Assessing Pupils' Progress

    ERIC Educational Resources Information Center

    Ollerton, Mike

    2010-01-01

    In this article, the author explores what Assessing Pupils' Progress (APP) is about. He contends that the predilection for testing is a catastrophe as far as the teaching and learning of mathematics is concerned; it is an outcome of the drive for collecting so-called "data" on pupils. What those people, who should know better, either choose to…

  3. Learning Progressions & Climate Change

    ERIC Educational Resources Information Center

    Parker, Joyce M.; de los Santos, Elizabeth X.; Anderson, Charles W.

    2015-01-01

    Our society is currently having serious debates about sources of energy and global climate change. But do students (and the public) have the requisite knowledge to engage these issues as informed citizenry? The learning-progression research summarized here indicates that only 10% of high school students typically have a level of understanding…

  4. Progressive Response Surfaces

    NASA Technical Reports Server (NTRS)

    Romero, V. J.; Swiler, L. P.

    2004-01-01

    Response surface functions are often used as simple and inexpensive replacements for computationally expensive computer models that simulate the behavior of a complex system over some parameter space. Progressive response surfaces are ones that are built up progressively as global information is added from new sample points in the parameter space. As the response surfaces are globally upgraded based on new information, heuristic indications of the convergence of the response surface approximation to the exact (fitted) function can be inferred. Sampling points can be incrementally added in a structured fashion, or in an unstructured fashion. Whatever the approach, at least in early stages of sampling it is usually desirable to sample the entire parameter space uniformly. At later stages of sampling, depending on the nature of the quantity being resolved, it may be desirable to continue sampling uniformly over the entire parameter space (Progressive response surfaces), or to switch to a focusing/economizing strategy of preferentially sampling certain regions of the parameter space based on information gained in early stages of sampling (Adaptive response surfaces). Here we consider Progressive response surfaces where a balanced indication of global response over the parameter space is desired.We use a variant of Moving Least Squares to fit and interpolate structured and unstructured point sets over the parameter space. On a 2-D test problem we compare response surface accuracy for three incremental sampling methods: Progressive Lattice Sampling; Simple-Random Monte Carlo; and Halton Quasi-Monte-Carlo sequences. We are ultimately after a system for constructing efficiently upgradable response surface approximations with reliable error estimates.

  5. Orion Absolute Navigation System Progress and Challenge

    NASA Technical Reports Server (NTRS)

    Holt, Greg N.; D'Souza, Christopher

    2012-01-01

    The absolute navigation design of NASA's Orion vehicle is described. It has undergone several iterations and modifications since its inception, and continues as a work-in-progress. This paper seeks to benchmark the current state of the design and some of the rationale and analysis behind it. There are specific challenges to address when preparing a timely and effective design for the Exploration Flight Test (EFT-1), while still looking ahead and providing software extensibility for future exploration missions. The primary onboard measurements in a Near-Earth or Mid-Earth environment consist of GPS pseudo-range and delta-range, but for future explorations missions the use of star-tracker and optical navigation sources need to be considered. Discussions are presented for state size and composition, processing techniques, and consider states. A presentation is given for the processing technique using the computationally stable and robust UDU formulation with an Agee-Turner Rank-One update. This allows for computational savings when dealing with many parameters which are modeled as slowly varying Gauss-Markov processes. Preliminary analysis shows up to a 50% reduction in computation versus a more traditional formulation. Several state elements are discussed and evaluated, including position, velocity, attitude, clock bias/drift, and GPS measurement biases in addition to bias, scale factor, misalignment, and non-orthogonalities of the accelerometers and gyroscopes. Another consideration is the initialization of the EKF in various scenarios. Scenarios such as single-event upset, ground command, and cold start are discussed as are strategies for whole and partial state updates as well as covariance considerations. Strategies are given for dealing with latent measurements and high-rate propagation using multi-rate architecture. The details of the rate groups and the data ow between the elements is discussed and evaluated.

  6. Intracellular Locations of Replication Proteins and the Origin of Replication during Chromosome Duplication in the Slowly Growing Human Pathogen Helicobacter pylori

    PubMed Central

    Sharma, Atul; Kamran, Mohammad; Verma, Vijay

    2014-01-01

    We followed the position of the replication complex in the pathogenic bacterium Helicobacter pylori using antibodies raised against the single-stranded DNA binding protein (HpSSB) and the replicative helicase (HpDnaB). The position of the replication origin, oriC, was also localized in growing cells by fluorescence in situ hybridization (FISH) with fluorescence-labeled DNA sequences adjacent to the origin. The replisome assembled at oriC near one of the cell poles, and the two forks moved together toward the cell center as replication progressed in the growing cell. Termination and resolution of the forks occurred near midcell, on one side of the septal membrane. The duplicated copies of oriC did not separate until late in elongation, when the daughter chromosomes segregated into bilobed nucleoids, suggesting sister chromatid cohesion at or near the oriC region. Components of the replication machinery, viz., HpDnaB and HpDnaG (DNA primase), were found associated with the cell membrane. A model for the assembly and location of the H. pylori replication machinery during chromosomal duplication is presented. PMID:24363345

  7. Progressive compressive imager

    NASA Astrophysics Data System (ADS)

    Evladov, Sergei; Levi, Ofer; Stern, Adrian

    2012-06-01

    We have designed and built a working automatic progressive sampling imaging system based on the vector sensor concept, which utilizes a unique sampling scheme of Radon projections. This sampling scheme makes it possible to progressively add information resulting in tradeoff between compression and the quality of reconstruction. The uniqueness of our sampling is that in any moment of the acquisition process the reconstruction can produce a reasonable version of the image. The advantage of the gradual addition of the samples is seen when the sparsity rate of the object is unknown, and thus the number of needed measurements. We have developed the iterative algorithm OSO (Ordered Sets Optimization) which employs our sampling scheme for creation of nearly uniform distributed sets of samples, which allows the reconstruction of Mega-Pixel images. We present the good quality reconstruction from compressed data ratios of 1:20.

  8. Photovoltaic concentrator research progress

    SciTech Connect

    Arvizu, D.E.

    1985-01-01

    This paper provides a review of progress in the DOE sponsored, Sandia managed Photovoltaic Concentrator Research Project. Research status, project goals and a discussion of concentrator economics is presented. Recent research accomplishments that will be discussed include 21% efficient baseline silicon cells by Applied Solar Energy Corporation and Sandia, 26% efficient GaAs cells by Varian Associates, and near 25% mechanically stacked multijunction GaAs/Si cells by Hughes Research, Applied Solar, and Sandia. In addition, improvements in breadboard module units (i.e. single lens/cell combination) such as a 19% GaAs unit by Varian and a near 17% silicon unit by ENTECH will be reviewed. This paper concludes that the photovoltaic concentrator option is making excellent progress toward competitive cost-effectiveness and provides a strong photovoltaic alternative.

  9. The Role of Astrocytes in Multiple Sclerosis Progression

    PubMed Central

    Correale, Jorge; Farez, Mauricio F.

    2015-01-01

    Multiple sclerosis (MS) is an inflammatory disorder causing central nervous system (CNS) demyelination and axonal injury. Although its etiology remains elusive, several lines of evidence support the concept that autoimmunity plays a major role in disease pathogenesis. The course of MS is highly variable; nevertheless, the majority of patients initially present a relapsing–remitting clinical course. After 10–15 years of disease, this pattern becomes progressive in up to 50% of untreated patients, during which time clinical symptoms slowly cause constant deterioration over a period of many years. In about 15% of MS patients, however, disease progression is relentless from disease onset. Published evidence supports the concept that progressive MS reflects a poorly understood mechanism of insidious axonal degeneration and neuronal loss. Recently, the type of microglial cell and of astrocyte activation and proliferation observed has suggested contribution of resident CNS cells may play a critical role in disease progression. Astrocytes could contribute to this process through several mechanisms: (a) as part of the innate immune system, (b) as a source of cytotoxic factors, (c) inhibiting remyelination and axonal regeneration by forming a glial scar, and (d) contributing to axonal mitochondrial dysfunction. Furthermore, regulatory mechanisms mediated by astrocytes can be affected by aging. Notably, astrocytes might also limit the detrimental effects of pro-inflammatory factors, while providing support and protection for oligodendrocytes and neurons. Because of the dichotomy observed in astrocytic effects, the design of therapeutic strategies targeting astrocytes becomes a challenging endeavor. Better knowledge of molecular and functional properties of astrocytes, therefore, should promote understanding of their specific role in MS pathophysiology, and consequently lead to development of novel and more successful therapeutic approaches. PMID:26347709

  10. Progression of myopia.

    PubMed Central

    Kennedy, R H

    1995-01-01

    BACKGROUND: Myopia is an important public health problem because it is common and is associated with increased risk for chorioretinal degeneration, retinal detachment, and other vision-threatening abnormalities. In animals, ocular elongation and myopia progression can be lessened with atropine treatment. This study provides information about progression of myopia and atropine therapy for myopia in humans. METHODS: A total of 214 residents of Olmsted County, Minnesota (118 girls and 96 boys; median age, 11 years; range, 6 to 15 years) received atropine for myopia from 1967 through 1974. Control subjects were matched by age, sex, refractive error, and date of baseline examination to 194 of those receiving atropine. Duration of treatment with atropine ranged from 18 weeks to 11.5 years (median 3.5 years). RESULTS: Median follow-up from initial to last refraction in the atropine group (11.7 years) was similar to that in the control group (12.4 years). Photophobia and blurred vision were frequently reported, but no serious adverse effects were associated with atropine therapy. Mean myopia progression during atropine treatment adjusted for age and refractive error (0.05 diopters per year) was significantly less than that among control subjects (0.36 diopters per year) (P < .001). Final refractions standardized to the age of 20 years showed a greater mean level of myopia in the control group (3.78 diopters) than in the atropine group (2.79 diopters) (P < .001). CONCLUSIONS: The data support the view that atropine therapy is associated with decreased progression of myopia and that beneficial effects remain after treatment has been discontinued. PMID:8719698

  11. ISABELLE: a progress report

    SciTech Connect

    Hahn, H

    1980-01-01

    This paper discusses the ISABELLE project, which has the objective of constructing a high-energy proton colliding beam facility at Brookhaven National Laboratory. The major technical features of the intersecting storage accelerators with their projected performance are described. Application of over 1000 superconducting magnets in the two rings represents the salient characteristic of the machine. The status of the entire project, the technical progress made so far, and difficulties encountered are reviewed.

  12. Progress in Scientific Visualization

    SciTech Connect

    Max, N

    2004-11-15

    Visualization of observed data or simulation output is important to science and engineering. I have been particularly interested in visualizing 3-D structures, and report here my personal impressions on progress in the last 20 years in visualizing molecules, scalar fields, and vector fields and their associated flows. I have tried to keep the survey and list of references manageable, so apologize to those authors whose techniques I have not mentioned, or have described without a reference citation.

  13. Progress In Holographic Cinematography

    NASA Astrophysics Data System (ADS)

    Smigielski, P.; Fagot, H.; Albe, F.

    1986-06-01

    Two important progresses were achieved for the first time: 1) recording of single exposure cineholograms of living bodies on a 126-mm film, at a frequency of 25 holograms per second. Limitations of 3-D movies by holography are described. 2) recording of double-exposure cineholograms of reflecting objects, a loudspeaker membrane and the vertex cranii of a bald-headed man. These experiments show the interest of interferometric cineholography for industrial applications.

  14. COSMIC monthly progress report

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Activities of the Computer Software Management and Information Center (COSMIC) are summarized for the month of January 1994. Tables showing the current inventory of programs available from COSMIC are presented and program processing and evaluation activities are discussed. Marketing and customer service activities in this period are presented as is the progress report of NASTRAN maintenance and support. Tables of disseminations and budget summary conclude the report.

  15. Primary-Progressive MS (PPMS)

    MedlinePlus

    ... MS? Types of MS Primary progressive MS (PPMS) Primary progressive MS (PPMS) Share Smaller Text Larger Text Print In this article Overview PPMS is characterized by worsening neurologic function ( ...

  16. Muscle MRI findings in limb girdle muscular dystrophy type 2L.

    PubMed

    Sarkozy, Anna; Deschauer, Marcus; Carlier, Robert-Yves; Schrank, Bertold; Seeger, Jürgen; Walter, Maggie C; Schoser, Benedikt; Reilich, Peter; Leturq, France; Radunovic, Aleksandar; Behin, Anthony; Laforet, Pascal; Eymard, Bruno; Schreiber, Herbert; Hicks, Debbie; Vaidya, Sujit S; Gläser, Dieter; Carlier, Pierre G; Bushby, Kate; Lochmüller, Hanns; Straub, Volker

    2012-10-01

    Limb girdle muscular dystrophy type 2L (LGMD2L) is an adult-onset slowly progressive muscular dystrophy associated with recessive mutations in the ANO5 gene. We analysed the muscle MRI pattern in a cohort of 25 LGMD2L patients in order to understand the extent and progression of muscle pathology in LGM2L and assess if muscle MRI might help in the diagnostic work-up of these patients. Our results showed a homogeneous pattern of muscle pathology on muscle MRI, with a predominant involvement of the posterior compartment muscles in both the thighs and calves. The muscles of the anterior compartments in the leg together with the sartorius and gracilis muscles were best preserved, which partially overlaps with patterns observed for other recessive LGMDs. Muscle MRI therefore does not appear to be as useful in the diagnostic work up of LGMD2L as for other neuromuscular diseases, such as Bethlem myopathy or myofibrillar myopathy. PMID:22980763

  17. Cochleo-saccular degeneration in one of three sisters with hereditary deafness, absent gastric motility, small bowel diverticulitis and progressive sensory neuropathy.

    PubMed

    Igarashi, M; MacRae, D; O-Uchi, T; Alford, B R

    1981-01-01

    This is a report of cochleo-saccular degeneration found in temporal bones from a patient who had suffered from slowly progressive and total sensorineural deafness which had an inherited origin. At age 8, this patient began to complain of hearing loss, and by age 10 she was totally deaf. The patient was 1 of 3 female siblings who have suffered from an exactly identical progressive disease: deafness, absent gastric motility, small bowel diverticulitis and ulceration, and sensory neuropathy. The temporal bone pathology found in this case was the degenerative change in the cochlear duct and sacculus. No pathology was found in the utriculus and semicircular canals. PMID:6937848

  18. Rapidly Progressing Chagas Cardiomyopathy.

    PubMed

    Hollowed, John; McCullough, Matthew; Sanchez, Daniel; Traina, Mahmoud; Hernandez, Salvador; Murillo, Efrain

    2016-04-01

    Chagas disease, caused by the parasiteTrypanosoma cruzi, can cause a potentially life-threatening cardiomyopathy in approximately 10-40% of afflicted individuals. The decline in cardiac function characteristically progresses over the course of many years. We report a case of Chagas disease in which the patient experienced an atypical rapid deterioration to severe cardiomyopathy over the course of 16 months. This case argues the need for increased routine surveillance for patients with confirmedT. cruziinfection, who are determined to be at high-risk for worsening cardiomyopathy. PMID:26856912

  19. HSX progress report

    SciTech Connect

    Not Available

    1994-05-01

    Brief statements on the progress of the design and construction of the HSX experiment are reported. Topics covered include the modular and auxiliary coil systems, the coil support structure, vacuum vessel, the ECH system, the magnet power supply and site. The proposed budget for Year 2 (August 1, 1994 through July 31, 1995) is presented. The effects of a flat funding profile (based on Year 2 budget level of $1137K) on out-years and the HSX project schedule are discussed. The stretching out of the program to accommodate the reduced funding profile should result in only a slight delay in HSX operations.

  20. PROGRESS ON STELLA EXPERIMENT.

    SciTech Connect

    KIMURA,W.D.; CAMPBELL,L.P.; GOTTSCHALK,S.C.; QUIMBY,D.C.; ROBINSON,K.E.; STEINHAUER,L.C.; BABZIEN,M.; BEN-ZVI,I.; GALLARDO,J.C.; KUSCHE,K.P.; POGORELSKY,I.V.; SKARITKA,J.; VAN STEENBERGEN,A.; YAKIMENKO,V.; CLINE,D.B.; HE,P.; LIU,Y.; FIORITO,R.B.; PANTELL,R.H.; RULE,D.W.; SANDWEISS,J.

    1999-03-01

    Progress is reported on the Staged Electron Laser Acceleration (STELLA) experiment, which has been assembled on the BNL Accelerator Test Facility (ATF). The primary goal of STELLA is to demonstrate staging of the laser acceleration process by using the BNL inverse free electron laser (IFEL) as a prebuncher, which generates {approx} 1-{micro}m long microbunches, and accelerating these microbunches using an inverse Cerenkov acceleration (ICA) stage. Experimental runs are underway to recommission the IFEL and ICA systems separately, and reestablish the: microbunching process. Staging will then be examined by running both the IFEL and ICA systems together.

  1. MEIC Design Progress

    SciTech Connect

    Zhang, Y; Douglas, D; Hutton, A; Krafft, G A; Li, R; Lin, F; Morozov, V S; Nissen, E W; Pilat, F C; Satogata, T; Tennant, C; Terzic, B; Yunn, C; Barber, D P; Filatov, Y; Hyde, C; Kondratenko, A M; Manikonda, S L; Ostroumov, P N; Sullivan, M K

    2012-07-01

    This paper will report the recent progress in the conceptual design of MEIC, a high luminosity medium energy polarized ring-ring electron-ion collider at Jefferson lab. The topics and achievements that will be covered are design of the ion large booster and the ERL-circulator-ring-based electron cooling facility, optimization of chromatic corrections and dynamic aperture studies, schemes and tracking simulations of lepton and ion polarization in the figure-8 collider ring, and the beam-beam and electron cooling simulations. A proposal of a test facility for the MEIC electron cooler will also be discussed.

  2. Post Kalman progress

    NASA Technical Reports Server (NTRS)

    Sonnabend, David

    1995-01-01

    In a paper here last year, an idea was put forward that much greater performance could be obtained from an observer, relative to a Kalman filter if more general performance indices were adopted, and the full power spectra of all the noises were employed. The considerable progress since then is reported here. Included are an extension of the theory to regulators, direct calculation of the theory's fundamental quantities - the noise effect integrals - for several theoretical spectra, and direct derivations of the Riccati equations of LQG (Linear-Quadratic-Gaussian) and Kalman theory yielding new insights.

  3. Co-induction of the heat shock response ameliorates disease progression in a mouse model of human spinal and bulbar muscular atrophy: implications for therapy

    PubMed Central

    Malik, Bilal; Nirmalananthan, Niranjanan; Gray, Anna L.; La Spada, Albert R.; Hanna, Michael G.

    2013-01-01

    Spinal and bulbar muscular atrophy, also known as Kennedy’s disease, is an adult-onset hereditary neurodegenerative disorder caused by an expansion of the polyglutamine repeat in the first exon in the androgen receptor gene. Pathologically, the disease is defined by selective loss of spinal and bulbar motor neurons causing bulbar, facial and limb weakness. Although the precise disease pathophysiology is largely unknown, it appears to be related to abnormal accumulation of the pathogenic androgen receptor protein within the nucleus, leading to disruption of cellular processes. Using a mouse model of spinal and bulbar muscular atrophy that exhibits many of the characteristic features of the human disease, in vivo physiological assessment of muscle function revealed that mice with the pathogenic expansion of the androgen receptor develop a motor deficit characterized by a reduction in muscle force, abnormal muscle contractile characteristics, loss of functional motor units and motor neuron degeneration. We have previously shown that treatment with arimoclomol, a co-inducer of the heat shock stress response, delays disease progression in the mutant superoxide dismutase 1 mouse model of amyotrophic lateral sclerosis, a fatal motor neuron disease. We therefore evaluated the therapeutic potential of arimoclomol in mice with spinal and bulbar muscular atrophy. Arimoclomol was administered orally, in drinking water, from symptom onset and the effects established at 18 months of age, a late stage of disease. Arimoclomol significantly improved hindlimb muscle force and contractile characteristics, rescued motor units and, importantly, improved motor neuron survival and upregulated the expression of the vascular endothelial growth factor which possess neurotrophic activity. These results provide evidence that upregulation of the heat shock response by treatment with arimoclomol may have therapeutic potential in the treatment of spinal and bulbar muscular atrophy and may also

  4. [An autopsy case of progressive generalized muscle atrophy over 14 years due to post-polio syndrome].

    PubMed

    Oki, Ryosuke; Uchino, Akiko; Izumi, Yuishin; Ogawa, Hirohisa; Murayama, Shigeo; Kaji, Ryuji

    2016-01-01

    We report the case of a 72-year-old man who had contracted acute paralytic poliomyelitis in his childhood. Thereafter, he had suffered from paresis involving the left lower limb, with no relapse or progression of the disease. He began noticing slowly progressive muscle weakness and atrophy in the upper and lower extremities in his 60s. At the age of 72, muscle weakness developed rapidly, and he demonstrated dyspnea on exertion and dysphagia. He died after about 14 years from the onset of muscle weakness symptoms. Autopsy findings demonstrated motoneuron loss and glial scars not only in the plaque-like lesions in the anterior horns, which were sequelae of old poliomyelitis, but also throughout the spine. No Bunina bodies, TDP-43, and ubiquitin inclusions were found. Post-polio syndrome is rarely fatal due to rapid progressive dyspnea and dysphagia. Thus, the pathological findings in the patient are considered to be related to the development of muscle weakness. PMID:26616485

  5. Neuropsychiatric aspects of adult-onset Tay-Sachs disease: two case reports with several new findings.

    PubMed

    Hurowitz, G I; Silver, J M; Brin, M F; Williams, D T; Johnson, W G

    1993-01-01

    Deficiency of hexosaminidase A causes the GM2 gangliosidosis known as Tay-Sachs disease. It is now known that this condition has several late-onset variants that cause numerous neuropsychiatric disturbances. Early recognition is important because treatment with phenothiazines and heterocyclic antidepressants may worsen the course. The authors report two cases with several new findings, including prominent psychiatric symptoms without psychosis early in the course of the illness. PMID:8428133

  6. Age at First Drink and the First Incidence of Adult-Onset DSM-IV Alcohol Use Disorders

    PubMed Central

    Dawson, Deborah A.; Goldstein, Risë B.; Chou, S. Patricia; Ruan, W. June; Grant, Bridget F.

    2008-01-01

    Background Existing studies of the association between age at first drink (AFD) and the risk of alcohol use disorders (AUD) suffer from inconsistent levels of control and designs that may inflate associations by failure to control for duration of exposure to risk. Methods This study examined associations between AFD (ages <15 and 15-17 versus 18+ years) and first incidence of DSM-IV alcohol dependence, abuse, and specific AUD criteria over a 3-year follow-up in a longitudinal study of U.S. drinkers 18 years of age and older at baseline (n=22,316), controlling for duration of exposure, family history and a wide range of baseline and childhood risk factors. Results After adjusting for all risk factors, the incidence of dependence was increased for AFD <15 years (OR=1.38) and for women only with AFD at ages 15-17 (OR=1.54). The incidence of abuse was increased at AFD <15 and 15-17 years (OR=1.52 and 1.30, respectively). Most dependence criteria showed significant associations with AFD, but hazardous drinking and continued drinking despite interpersonal problems were the only abuse criteria to do so. All associations were nonsignificant after controlling for volume of consumption, except that AFD at all ages <18 combined was associated with a reduced likelihood of impaired control and AFD at ages 15-17 was associated with lower odds of drinking more/longer than intended among heavy-volume drinkers. In a population of low-risk drinkers that excluded those with positive family histories, personality disorders and childhood risk factors, there were strong associations between early AFD (<18) and the incidence of dependence (OR=3.79) and continued drinking despite physical/psychological problems (OR=2.71), but no association with incidence of abuse. Conclusions There is a robust association between AFD and the risk of AUD that appears to reflect willful rather than uncontrolled heavy drinking, consistent with misuse governed by poor decision-making and/or reward-processing skills associated with impaired executive cognitive function (ECF). Additional research is needed to determine causality in the role of impaired ECF, including longitudinal studies with samples of low-risk adolescents. PMID:18828796

  7. Adult Onset-hypothyroidism has Minimal Effects on Synaptic Transmission in the Hippocampus of Rats Independent of Hypothermia

    EPA Science Inventory

    Introduction: Thyroid hormones (TH) influence central nervous system (CNS) function during development and in adulthood. The hippocampus, a brain area critical for learning and memory is sensitive to TH insufficiency. Synaptic transmission in the hippocampus is impaired following...

  8. Brief Report: No Association between Premorbid Adjustment in Adult-Onset Schizophrenia and Genetic Variation in Dysbindin

    ERIC Educational Resources Information Center

    Schirmbeck, Frederike; Georgi, Alexander; Strohmaier, Jana; Schmael, Christine; Boesshenz, Katja V.; Muhleisen, Thomas W.; Herms, Stefan; Hoffmann, Per; Jamra, Rami Abou; Schumacher, Johannes; Maier, Wolfgang; Propping, Peter; Nothen, Markus M.; Cichon, Sven; Rietschel, Marcella; Schulze, Thomas G.

    2008-01-01

    Whereas "Dysbindin" is considered a schizophrenia vulnerability gene, there is no consistency of findings. Phenotype refinement approaches may help to increase the genetic homogeneity and thus reconcile conflicting results. Premorbid adjustment (PMA) has been suggested to aid the phenotypic dissection. Gornick et al. ("J Autism Dev Disord"…

  9. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia.

    PubMed

    Deng, Han-Xiang; Chen, Wenjie; Hong, Seong-Tshool; Boycott, Kym M; Gorrie, George H; Siddique, Nailah; Yang, Yi; Fecto, Faisal; Shi, Yong; Zhai, Hong; Jiang, Hujun; Hirano, Makito; Rampersaud, Evadnie; Jansen, Gerard H; Donkervoort, Sandra; Bigio, Eileen H; Brooks, Benjamin R; Ajroud, Kaouther; Sufit, Robert L; Haines, Jonathan L; Mugnaini, Enrico; Pericak-Vance, Margaret A; Siddique, Teepu

    2011-09-01

    Amyotrophic lateral sclerosis (ALS) is a paralytic and usually fatal disorder caused by motor-neuron degeneration in the brain and spinal cord. Most cases of ALS are sporadic but about 5-10% are familial. Mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP, also known as TDP43) and fused in sarcoma (FUS, also known as translocated in liposarcoma (TLS)) account for approximately 30% of classic familial ALS. Mutations in several other genes have also been reported as rare causes of ALS or ALS-like syndromes. The causes of the remaining cases of familial ALS and of the vast majority of sporadic ALS are unknown. Despite extensive studies of previously identified ALS-causing genes, the pathogenic mechanism underlying motor-neuron degeneration in ALS remains largely obscure. Dementia, usually of the frontotemporal lobar type, may occur in some ALS cases. It is unclear whether ALS and dementia share common aetiology and pathogenesis in ALS/dementia. Here we show that mutations in UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS and ALS/dementia. We describe novel ubiquilin 2 pathology in the spinal cords of ALS cases and in the brains of ALS/dementia cases with or without UBQLN2 mutations. Ubiquilin 2 is a member of the ubiquilin family, which regulates the degradation of ubiquitinated proteins. Functional analysis showed that mutations in UBQLN2 lead to an impairment of protein degradation. Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention. PMID:21857683

  10. Yoga decreases kyphosis in senior women and men with adult onset hyperkyphosis: results of a randomized controlled trial

    PubMed Central

    Greendale, Gail A.; Huang, Mei-Hua; Karlamangla, Arun S.; Seeger, Leanne; Crawford, Sybil

    2013-01-01

    Objective To assess whether a specifically designed Yoga intervention can reduce hyperkyphosis. Design A 6-month, 2 group, randomized, controlled, single masked trial. Setting Community research unit. Participants 118 women and men aged >60 years with kyphosis angle >40 degrees. Major exclusions were: serious medical comorbidity; use of assistive device; unable to hear or see adequately for participation; or unable to pass a physical safety screen. Intervention The active treatment group attended hour-long Yoga classes, 3 days per week, for 24 weeks. The control group attended a monthly luncheon/seminar and received mailings. Measurements Primary outcomes were change (baseline to 6 months) in Debrunner kyphometer-assessed kyphosis angle, standing height, timed chair stands, functional reach and walking speed. Secondary outcomes were change in: kyphosis index, flexicurve kyphosis angle, the Rancho Bernardo Blocks posture assessment and health-related quality of life (HRQOL). Results Compared to control participants, those randomized to Yoga experienced a 4.4% improvement in flexicurve kyphosis angle (p=0.006) and a 5% improvement in kyphosis index (p=0.004). The intervention did not result in statistically significant improvement in Debrunner kyphometer angle, measured physical performance or in self-assessed HRQOL (each p>0.1). Conclusion The decrease in flexicurve kyphosis angle in the Yoga treatment group shows that hyperkyphosis is remediable, a critical first step in the pathway to treating or preventing this condition. Larger, more definitive studies of Yoga or other interventions for hyperkyphosis should be considered. Targeting individuals with more malleable spines and using longitudinally precise measures of kyphosis could strengthen the treatment effect. PMID:19682114

  11. Congenital and prolonged adult-onset deafness cause distinct degradations in neural ITD coding with bilateral cochlear implants.

    PubMed

    Hancock, Kenneth E; Chung, Yoojin; Delgutte, Bertrand

    2013-06-01

    Bilateral cochlear implant (CI) users perform poorly on tasks involving interaural time differences (ITD), which are critical for sound localization and speech reception in noise by normal-hearing listeners. ITD perception with bilateral CI is influenced by age at onset of deafness and duration of deafness. We previously showed that ITD coding in the auditory midbrain is degraded in congenitally deaf white cats (DWC) compared to acutely deafened cats (ADC) with normal auditory development (Hancock et al., J. Neurosci, 30:14068). To determine the relative importance of early onset of deafness and prolonged duration of deafness for abnormal ITD coding in DWC, we recorded from single units in the inferior colliculus of cats deafened as adults 6 months prior to experimentation (long-term deafened cats, LTDC) and compared neural ITD coding between the three deafness models. The incidence of ITD-sensitive neurons was similar in both groups with normal auditory development (LTDC and ADC), but significantly diminished in DWC. In contrast, both groups that experienced prolonged deafness (LTDC and DWC) had broad distributions of best ITDs around the midline, unlike the more focused distributions biased toward contralateral-leading ITDs present in both ADC and normal-hearing animals. The lack of contralateral bias in LTDC and DWC results in reduced sensitivity to changes in ITD within the natural range. The finding that early onset of deafness more severely degrades neural ITD coding than prolonged duration of deafness argues for the importance of fitting deaf children with sound processors that provide reliable ITD cues at an early age. PMID:23462803

  12. Pediatric, elderly, and emerging adult-onset peaks in Burkitt lymphoma incidence diagnosed in four continents, excluding Africa

    PubMed Central

    Mbulaiteye, Sam M.; Anderson, William F.; Ferlay, Jacques; Bhatia, Kishor; Chang, Cindy; Rosenberg, Philip S.; Devesa, Susan S.; Parkin, Donald M.

    2012-01-01

    Burkitt lymphoma (BL) in the general population and immunosuppressed persons with AIDS in United States was characterized by three age-specific incidence peaks near 10, 40 and 70 years. We hypothesized that BL from different geographical areas may exhibit pediatric, adult, and elderly age incidence peaks. We investigated this hypothesis using data on 3403 cases obtained from the International Agency for Research on Cancer (1978–2002). Data from Africa were sparse or incomplete, and thus were excluded. Age-standardized rates (ASR) and age-specific incidence rates were calculated, supplemented with calculations performed using age-period-cohort models. The ASR rose 5.3% (95% confidence interval (CI), 5.0–5.6) per year in males and 4.6% (95% CI, 4.5–4.8) in females. The ASR increased gradually in children and steeply in adults and most rapidly in the elderly both in males and females. Overall, BL male/female ASR ratio was 2.5, but it declined from 3.1 (95% CI, 3.0–3.3) for pediatric BL to 2.3 (95% CI 2.2–2.4) for adult BL and 1.5 (95% CI, 1.4–1.6) for elderly BL. Age-specific incidence peaks occurred near 10 years and 70 years in all regions and periods. A peak near 40 years of age emerged in the mid-1990s, particularly in men. Findings using APC models confirmed those based on standard analyses. Our findings, based on international BL cases, support our hypothesis that BL is multimodal and that BL peaks at different ages may be clues to differences in the etiology and/or biology of BL at those ages. PMID:22488262

  13. Adult-onset hyperthyroidism impairs spatial learning: possible involvement of mitogen-activated protein kinase signaling pathways.

    PubMed

    Bitiktaş, Soner; Kandemir, Başak; Tan, Burak; Kavraal, Şehrazat; Liman, Narin; Dursun, Nurcan; Dönmez-Altuntaş, Hamiyet; Aksan-Kurnaz, Işil; Suer, Cem

    2016-08-01

    Given evidence that mitogen-activated protein kinase (MAPK) activation is part of the nongenomic actions of thyroid hormones, we investigated the possible consequences of hyperthyroidism for the cognitive functioning of adult rats. Young adult rats were treated with L-thyroxine or saline. Twenty rats in each group were exposed to Morris water maze testing, measuring their performance in a hidden-platform spatial task. In a separate set of rats not exposed to Morris water maze testing (untrained rats), the expression and phosphorylated levels of p38-MAPK and of its two downstream effectors, Elk-1 and cAMP response element-binding protein, were evaluated using quantitative reverse transcriptase-PCR and western blotting. Rats with hyperthyroidism showed delayed acquisition of learning compared with their wild-type counterparts, as shown by increased escape latencies and distance moved on the last two trials of daily training in the water maze. The hyperthyroid rats, however, showed no difference during probe trials. Western blot analyses of the hippocampus showed that hyperthyroidism increased phosphorylated p38-MAPK levels in untrained rats. Although our study is correlative in nature and does not exclude the contribution of other molecular targets, our findings suggest that the observed impairments in acquisition during actual learning in rats with hyperthyroidism may result from the increased phosphorylation of p38-MAPK. PMID:27258653

  14. Observational clinical study of 22 adult-onset Pompe disease patients undergoing enzyme replacement therapy over 5years.

    PubMed

    Stepien, Karolina M; Hendriksz, Christian J; Roberts, Mark; Sharma, Reena

    2016-04-01

    Pompe disease is an autosomal recessive disease resulting from deficiency of the acid alpha-glucosidase (GAA). The late-onset Pompe Disease (LOPD) patients develop muscular and respiratory complications later in life. We describe a retrospective observational cohort study including 22 patients with LOPD. The cohort was assessed at baseline before Enzyme Replacement Therapy (ERT) with alglucosidase alpha (20mg/kg biweekly) was commenced and subsequently relevant information was collected at 2, 4 and 5years later. The median age of the patients at study entry was 44years (16-64years), with median disease duration of 11.5years (4-31years). At baseline, 10 patients (45%) could walk without support, 12 (55%) could walk with unilateral or bilateral support including 3/12 were wheelchair bound. Mean predicted FVC % was 55.7 (95% CI 45-66) of predicted normal at baseline and showed no significant change after 5years (54.6 (95% CI 43-66)), (all p=0.9815). Mean FVC % supine was 41.8 (95% CI 33.8-49) of predicted normal at baseline and remained significantly unchanged at 5years (48.4 (95% CI 37-59.6)), (all p=0.8680). The overnight non-invasive ventilator dependence increased by 18.2% as compared with baseline and requirement of mobility aids increased during this period by 5.2% as compared with the baseline. Mean walking distance at 6min walk test was 411.5 (95% CI 338-485) at baseline, 266.5 (95% CI 187-346) m at 2years, 238.6 (95% CI 162-315) m at 4years and 286.8 (95% CI 203-370) m at 5years (p=0.1981; ANOVA was completed only for 14 patients). A gradual decline in FVC% predicted was noted only in four cases and a decline in FVC% supine in two other. Only one patient showed a decline in both pulmonary function tests. In all remaining cases (17/22) respiratory function remains stable. In conclusion overall pulmonary function tests and mobility remained stable for 5years in majority of patients on ERT. However, in some patients they continued to decline in spite of ERT resulting in increased number of patients requiring ventilation and increase wheel chair dependence at the end of 5years. PMID:26873529

  15. Conceptions of Progress: How Is Progress Perceived? Mainstream versus Alternative Conceptions of Progress

    ERIC Educational Resources Information Center

    Itay, Anat

    2009-01-01

    Progress is a powerful political concept, encompassing different and sometimes contradictory conceptions. This paper examines the results of a survey on progress conducted at the OECD World Forum entitled "Measuring and Fostering the Progress of Societies" held in Istanbul in June 2007. First, a distinction is drawn between the two approaches to…

  16. Progressive myoclonic epilepsy.

    PubMed

    Satishchandra, P; Sinha, S

    2010-01-01

    Progressive myoclonic epilepsy (PME) is a disease complex and is characterized by the development of relentlessly progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. It encompasses different diagnostic entities and the common causes include Lafora body disease, neuronal ceroid lipofuscinoses, Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fiber (MERRF) syndrome, sialidoses, dentato-rubro-pallidal atrophy, storage diseases, and some of the inborn errors of metabolism, among others. Recent advances in this area have clarified molecular genetic basis, biological basis, and natural history, and also provided a rational approach to the diagnosis. Most of the large studies related to PME are from south India from a single center, National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore. However, there are a few case reports and small series about Lafora body disease, neuronal ceroid lipofuscinoses and MERRF from India. We review the clinical and research experience of a cohort of PME patients evaluated at NIMHANS over the last two decades, especially the phenotypic, electrophysiologic, pathologic, and genetic aspects. PMID:20739785

  17. The Progressive Era.

    PubMed

    Chambers, David W

    2005-01-01

    The American College of Dentists was founded in 1920 for the purpose of encouraging young dentists to continue study and to apply science to their practices. This ideal emerged in the Progressive Era, which lasted roughly from 1895 to 1920. The animating spirit of this period was that the human condition could be improved and that the way to achieve this was through science and the use of experts working together. The Progressive Era saw inventions, such as automobiles and airplanes, telephone and radio, that required mass production and brought people together. It also spawned many political and legislative innovations that we now take for granted. Among these are the Food and Drug Administration, the Department of Commerce, and the Federal Trade Commission. Workers' compensation and other social protections were introduced, as were city commissions; the income tax; women's suffrage; and initiative, referendum, and recall. Medicine, for the first time, became an effective way to treat disease as it developed a scientific foundation. PMID:16350929

  18. Progressive myoclonus epilepsy.

    PubMed

    Girard, Jean-Marie; Turnbull, Julie; Ramachandran, Nivetha; Minassian, Berge A

    2013-01-01

    The progressive myoclonus epilepsies (PMEs) consist of a group of diseases with myoclonic seizures and progressive neurodegeneration, with onset in childhood and/or adolescence. Lafora disease is a neuronal glycogenosis in which normal glycogen is transformed into starch-like polyglucosans that accumulate in the neuronal somatodendritic compartment. It is caused by defects of two genes of yet unknown function, one encoding a glycogen phosphatase (laforin) and the other an ubiquitin E3 ligase (malin). Early cognitive deterioration, visual seizures affecting over half, and slowing down of EEG basic activity are three major diagnostic clues. Unverricht-Lundborg disease is presently thought to be due to damage to neurons by lysosomal cathepsins and reactive oxygen species due to absence of cystatin B, a small protein that inactivates cathepsins and, by ways yet unknown, quenches damaging redox compounds. Preserved cognition and background EEG activity, action myoclonus early morning and vertex spikes in REM sleep are the diagnostic clues. Sialidosis, with cherry-red spot, neuronopathic Gaucher disease, with paralysis of verticality, and ataxia-PME, with ataxia at onset in the middle of the first decade, are also lysosomal diseases. How the lysosomal defect culminates in myoclonus and epilepsy in these conditions remains unknown. PMID:23622396

  19. Cataract progression in India

    PubMed Central

    Srinivasan, M; Rahmathullah, R.; Blair, C.; Murphy, A.; Beck, R.; Wilkins, J.; Whitcher, J.; Smolin, G.

    1997-01-01

    AIMS—The study was undertaken to test the feasibility of using the LOCS III cataract grading scale in the field and to determine the rate of cataract progression over a 1 year period of time.
METHODS—For 150 subjects between the ages of 33 and 55 who attended the refraction clinic at Aravind Eye Hospital in Madurai, India, lens abnormalities were graded at the slit lamp using the LOCS III scale. One year later, 99 of the subjects were re-evaluated by the same methodology to assess the amount of lens change.
RESULTS—Interrater reliability was high. A change of 0.5 or more in lens colour, cortical, nuclear, or posterior subcapsular cataract was observed in at least one eye of 54% of the subjects.
CONCLUSION—The LOCS III grading scale is a feasible method for measuring lens changes in the field with the slit lamp. Cataract progression in India is rapid enough to permit intervention studies to be performed with relatively small numbers of subjects over a short period of time (that is, 600 subjects for 2 years).

 PMID:9486033

  20. Progressive Precision Surface Design

    SciTech Connect

    Duchaineau, M; Joy, KJ

    2002-01-11

    We introduce a novel wavelet decomposition algorithm that makes a number of powerful new surface design operations practical. Wavelets, and hierarchical representations generally, have held promise to facilitate a variety of design tasks in a unified way by approximating results very precisely, thus avoiding a proliferation of undergirding mathematical representations. However, traditional wavelet decomposition is defined from fine to coarse resolution, thus limiting its efficiency for highly precise surface manipulation when attempting to create new non-local editing methods. Our key contribution is the progressive wavelet decomposition algorithm, a general-purpose coarse-to-fine method for hierarchical fitting, based in this paper on an underlying multiresolution representation called dyadic splines. The algorithm requests input via a generic interval query mechanism, allowing a wide variety of non-local operations to be quickly implemented. The algorithm performs work proportionate to the tiny compressed output size, rather than to some arbitrarily high resolution that would otherwise be required, thus increasing performance by several orders of magnitude. We describe several design operations that are made tractable because of the progressive decomposition. Free-form pasting is a generalization of the traditional control-mesh edit, but for which the shape of the change is completely general and where the shape can be placed using a free-form deformation within the surface domain. Smoothing and roughening operations are enhanced so that an arbitrary loop in the domain specifies the area of effect. Finally, the sculpting effect of moving a tool shape along a path is simulated.

  1. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour’s survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  2. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  3. Primary progressive aphasia

    PubMed Central

    Mesulam, Marsel

    2014-01-01

    Primary progressive aphasia (PPA) is a clinical syndrome diagnosed when three core criteria are met. First, there should be a language impairment (i.e., aphasia) that interferes with the usage or comprehension of words. Second, the neurological work-up should determine that the disease is neurodegenerative, and therefore progressive. Third, the aphasia should arise in relative isolation, without equivalent deficits of comportment or episodic memory. The language impairment can be fluent or non-fluent and may or may not interfere with word comprehension. Memory for recent events is preserved although memory scores obtained in verbally mediated tests may be abnormal. Minor changes in personality and behavior may be present but are not the leading factors that bring the patient to medical attention or that limit daily living activities. This distinctive clinical pattern is most conspicuous in the initial stages of the disease, and reflects a relatively selective atrophy of the language network, usually located in the left hemisphere. There are different clinical variants of PPA, each with a characteristic pattern of atrophy. The underlying neuropathological diseases are heterogeneous and can include Alzheimer’s disease as well as frontotemporal lobar degeneration. The clinician’s task is to recognize PPA and differentiate it from other neurodegenerative phenotypes, use biomarkers to surmise the nature of the underlying neuropathology, and institute the most fitting multimodal interventions. PMID:24707349

  4. 2-Deoxy-d-Glucose Ameliorates PKD Progression.

    PubMed

    Chiaravalli, Marco; Rowe, Isaline; Mannella, Valeria; Quilici, Giacomo; Canu, Tamara; Bianchi, Veronica; Gurgone, Antonia; Antunes, Sofia; D'Adamo, Patrizia; Esposito, Antonio; Musco, Giovanna; Boletta, Alessandra

    2016-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of ESRD for which there exists no approved therapy in the United States. Defective glucose metabolism has been identified as a feature of ADPKD, and inhibition of glycolysis using glucose analogs ameliorates aggressive PKD in preclinical models. Here, we investigated the effects of chronic treatment with low doses of the glucose analog 2-deoxy-d-glucose (2DG) on ADPKD progression in orthologous and slowly progressive murine models created by inducible inactivation of the Pkd1 gene postnatally. As previously reported, early inactivation (postnatal days 11 and 12) of Pkd1 resulted in PKD developing within weeks, whereas late inactivation (postnatal days 25-28) resulted in PKD developing in months. Irrespective of the timing of Pkd1 gene inactivation, cystic kidneys showed enhanced uptake of (13)C-glucose and conversion to (13)C-lactate. Administration of 2DG restored normal renal levels of the phosphorylated forms of AMP-activated protein kinase and its target acetyl-CoA carboxylase. Furthermore, 2DG greatly retarded disease progression in both model systems, reducing the increase in total kidney volume and cystic index and markedly reducing CD45-positive cell infiltration. Notably, chronic administration of low doses (100 mg/kg 5 days per week) of 2DG did not result in any obvious sign of toxicity as assessed by analysis of brain and heart histology as well as behavioral tests. Our data provide proof of principle support for the use of 2DG as a therapeutic strategy in ADPKD. PMID:26534924

  5. Progressive Multifocal Leukoencephalopathy

    PubMed Central

    Adang, Laura; Berger, Joseph

    2015-01-01

    Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease with significant morbidity and mortality and no effective, targeted therapies. It is most often observed in association with abnormalities of cell-mediated immunity, in particular human immunodeficiency virus (HIV) infection, but also occurs in association with lymphoproliferative diseases, certain immunosuppressive and immunomodulatory regimens, and other conditions. The etiologic agent of PML is a small, ubiquitous polyomavirus, the JC virus (JCV, also known as JCPyV), for which at least 50% of the adult general population is seropositive. PML results when JCV replicates within cerebral oligodendrocytes and astrocytes, leading to oligodendrocyte death and demyelination. Unfortunately, no treatments have been convincingly demonstrated to be effective, though some have been employed in desperation; treatment otherwise includes attempts to restore any immune system defect, such as the withdrawal of the causative agent if possible, and general supportive care. PMID:26918152

  6. Progressing batch hydrolysis process

    DOEpatents

    Wright, John D.

    1986-01-01

    A progressive batch hydrolysis process for producing sugar from a lignocellulosic feedstock, comprising passing a stream of dilute acid serially through a plurality of percolation hydrolysis reactors charged with said feedstock, at a flow rate, temperature and pressure sufficient to substantially convert all the cellulose component of the feedstock to glucose; cooling said dilute acid stream containing glucose, after exiting the last percolation hydrolysis reactor, then feeding said dilute acid stream serially through a plurality of prehydrolysis percolation reactors, charged with said feedstock, at a flow rate, temperature and pressure sufficient to substantially convert all the hemicellulose component of said feedstock to glucose; and cooling the dilute acid stream containing glucose after it exits the last prehydrolysis reactor.

  7. Progressing batch hydrolysis process

    DOEpatents

    Wright, J.D.

    1985-01-10

    A progressive batch hydrolysis process is disclosed for producing sugar from a lignocellulosic feedstock. It comprises passing a stream of dilute acid serially through a plurality of percolation hydrolysis reactors charged with feed stock, at a flow rate, temperature and pressure sufficient to substantially convert all the cellulose component of the feed stock to glucose. The cooled dilute acid stream containing glucose, after exiting the last percolation hydrolysis reactor, serially fed through a plurality of pre-hydrolysis percolation reactors, charged with said feedstock, at a flow rate, temperature and pressure sufficient to substantially convert all the hemicellulose component of said feedstock to glucose. The dilute acid stream containing glucose is cooled after it exits the last prehydrolysis reactor.

  8. Progress Towards International Repositories

    SciTech Connect

    McCombie, C.; Chapman, N.

    2002-02-27

    The nuclear fuel cycle is designed to be very international, with some specialist activities (e.g. fuel fabrication, reprocessing, etc.) being confined to a few countries. Nevertheless, political and public opposition has in the past been faced by proposals to internationalise the back-end of the cycle, in particular waste disposal. Attitudes, however, have been changing recently and there is now more acceptance of the general concept of shared repositories and of specific proposals such as that of Pangea. However, as for national facilities, progress towards implementation of shared repositories will be gradual. Moreover, the best vehicle for promoting the concept may not be a commercial type of organization. Consequently the Pangea project team are currently establishing a widely based Association for this purpose.

  9. Progressive Band Selection

    NASA Technical Reports Server (NTRS)

    Fisher, Kevin; Chang, Chein-I

    2009-01-01

    Progressive band selection (PBS) reduces spectral redundancy without significant loss of information, thereby reducing hyperspectral image data volume and processing time. Used onboard a spacecraft, it can also reduce image downlink time. PBS prioritizes an image's spectral bands according to priority scores that measure their significance to a specific application. Then it uses one of three methods to select an appropriate number of the most useful bands. Key challenges for PBS include selecting an appropriate criterion to generate band priority scores, and determining how many bands should be retained in the reduced image. The image's Virtual Dimensionality (VD), once computed, is a reasonable estimate of the latter. We describe the major design details of PBS and test PBS in a land classification experiment.

  10. Progress in palaeotsunami research

    NASA Astrophysics Data System (ADS)

    Goff, James; Chagué-Goff, Catherine; Nichol, Scott; Jaffe, Bruce; Dominey-Howes, Dale

    2012-01-01

    The study of palaeotsunamis preserved in the sedimentary record has developed over the past three decades to a point where the criteria used to identify these events range from well-tested and accepted to new methods yet to receive wide application. In this paper we review progress with the development of these criteria and identify opportunities for refinements and for extending their application to new settings. The emphasis here is on promoting the use of multiple proxies, selected to best match the context of the site or region of interest. Ultimately, this requires that palaeotsunami research must be a multidisciplinary endeavour and indeed, extend beyond the geological sciences of sedimentology and stratigraphy and, to include knowledge and approaches from field such as archaeology, anthropology and sociology. We also argue that in some instances, despite the use of multiple proxies, the evidence for tsunami inundation of a coast simply may not be preserved.

  11. Muon collider progress

    SciTech Connect

    Noble, Robert J. FNAL

    1998-08-01

    Recent progress in the study of muon colliders is presented. An international collaboration consisting of over 100 individuals is involved in calculations and experiments to demonstrate the feasibility of this new type of lepton collider. Theoretical efforts are now concentrated on low-energy colliders in the 100 to 500 GeV center-of-mass energy range. Credible machine designs are emerging for much of a hypothetical complex from proton source to the final collider. Ionization cooling has been the most difficult part of the concept, and more powerful simulation tools are now in place to develop workable schemes. A collaboration proposal for a muon cooling experiment has been presented to the Fermilab Physics Advisory Committee, and a proposal for a targetry and pion collection channel experiment at Brookhaven National Laboratory is in preparation. Initial proton bunching and space-charge compensation experiments at existing hadron facilities have occurred to demonstrate proton driver feasibility.

  12. Progress toward synthetic cells.

    PubMed

    Blain, J Craig; Szostak, Jack W

    2014-01-01

    The complexity of even the simplest known life forms makes efforts to synthesize living cells from inanimate components seem like a daunting task. However, recent progress toward the creation of synthetic cells, ranging from simple protocells to artificial cells approaching the complexity of bacteria, suggests that the synthesis of life is now a realistic goal. Protocell research, fueled by advances in the biophysics of primitive membranes and the chemistry of nucleic acid replication, is providing new insights into the origin of cellular life. Parallel efforts to construct more complex artificial cells, incorporating translational machinery and protein enzymes, are providing information about the requirements for protein-based life. We discuss recent advances and remaining challenges in the synthesis of artificial cells, the possibility of creating new forms of life distinct from existing biology, and the promise of this research for gaining a deeper understanding of the nature of living systems. PMID:24606140

  13. Progressive supranuclear palsy.

    PubMed

    Boeve, Bradley F

    2012-01-01

    Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy which can manifest clinically in a variety of syndromes. In this review, the classic and most common variant syndrome -PSP-Richardson's syndrome (PSP-RS) -is the focus, with the core clinical features, varying cognitive/motor/neuropsychiatric/sleep manifestations, neuropsychological findings, and typical neuroimaging findings all reviewed. Management strategies are also discussed. Of particular interest are the recently commenced clinical trials involving agents which affect key steps in the presumed pathogenesis of the tauopathies. The distinctive and recognizable characteristics of PSP-RS and advent of clinical trials involving potential disease modifying agents underscore the importance of identifying patients with this disorder and encouraging their involvement in trials. PMID:22166432

  14. Sphingosylphosphorylcholine in cancer progress

    PubMed Central

    Yue, Hong-Wei; Jing, Qing-Chuan; Liu, Ping-Ping; Liu, Jing; Li, Wen-Jing; Zhao, Jing

    2015-01-01

    Sphingosylphosphorylcholine (SPC) is a naturally occurring bioactive sphingolipid in blood plasma, metabolizing from the hydrolysis of the membrane sphingolipid. It has been shown to exert multifunctional role in cell physiological regulation either as an intracellular second messenger or as an extracellular agent through G protein coupled receptors (GPCRs). Because of elevated levels of SPC in malicious ascites of patients with cancer, the role of SPC in tumor progression has prompted wide interest. The factor was reported to affect the proliferation and/or migration of many cancer cells, including pancreatic cancer cells, epithelial ovarian carcinoma cells, rat C6 glioma cells, neuroblastoma cells, melanoma cells, and human leukemia cells. This review covers current knowledge of the role of SPC in tumor. PMID:26550104

  15. Progress in Induction Linacs

    SciTech Connect

    Caporaso, G J

    2000-09-27

    This presentation will be a broad survey of progress in induction technology over the past four years. Much work has been done on accelerators for hydrodynamic test radiography and other applications. Solid-state pulsers have been developed which can provide unprecedented flexibility and precision in pulse format and accelerating voltage for both ion and electron induction machines. Induction linacs can now be built which can operate with MHz repetition rates. Solid-state technology has also made possible the development of fast kickers for precision control of high current beams. New insulator technology has been developed which will improve conventional induction linacs in addition to enabling a new class of high gradient induction linacs.

  16. Progress in Stockholm talks

    SciTech Connect

    Borawski, J.

    1986-02-01

    Public interest focuses on whether the superpowers will eventually agree to reduce their strategic nuclear arsenals by 50% or better, and on whether Star Wars should be bargained away or preserved at all costs. Yet progress in arms control quietly proceeded in Stockholm at the multilateral Conference on Confidence- and Security-Building Measures and Disarmament in Europe (CDE), convened on January 17, 1984. The Conference examined ways to reduce the risks of war, but not arbitrarily lowering weapons levels or restricting the deployment of certain systems. Rather, the goal is to lower these risks by clarifying politico-military intentions and regulating the uses of military activities by means of confidence- and security-building measures. Through information exchange, observation, and inspection, along with operational restraints on military activities, these measure seek to diminish the opportunities for wars to start by surprise attack, miscalculation, or accident, and to inhibit the threat or indirect use of force for political intimidation. 2 references.

  17. 1992 PVUSA progress report

    SciTech Connect

    1992-12-31

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale photovoltaic (PV) electric generating systems. This report updates the progress of the PVUSA project, reviews the status and performance of the various PV installations during 1992, and summarizes key accomplishments and conclusions from work to date. Fall PV module costs and rising environmental pressures could make PV a significant source of large-scale power within the next decade. However, utility acceptance of this technology requires knowledge of PV operational characteristics in a utility system and confidence in predicting PV performance, reliability, and economics. PVUSA consists of two types of demonstrations: Emerging Module Technologies (EMTs), which are unproven but promising state-of-the-art PV technologies in 20-kW (nominal) arrays; and Utility Scale (US) systems, which represent more mature PV technologies in 200- to 500-kW (nominal) turnkey systems.

  18. Predicting periodontitis progression?

    PubMed

    Ferraiolo, Debra M

    2016-03-01

    Data sourcesCochrane Library, Ovid, Medline, Embase and LILACS were searched using no language restrictions and included information up to July 2014. Bibliographic references of included articles and related review articles were hand searched. On-line hand searching of recent issues of key periodontal journals was performed (Journal of Clinical Periodontology, Journal of Dental Research, Journal of Periodontal Research, Journal of Periodontology, Oral Health and Preventive Dentistry).Study selectionProspective and retrospective cohort studies were used for answering the question of prediction since there were no randomised controlled trials on this topic. Risk of bias was assessed using the validated Newcastle-Ottawa quality assessment scale for non-randomised studies. Cross-sectional studies were included in the summary of currently reported risk assessment tools but not for risk of progression of disease, due to the inability to properly assess bias in these types of studies. Titles and abstracts were scanned by two reviewers independently.Full reports were obtained for those articles meeting inclusion criteria or those with insufficient information in the title to make a decision. Any published risk assessment tool was considered. The tool was defined to include any composite measure of patient-level risk directed towards determining the probability for further disease progression in adults with periodontitis. Periodontitis was defined to include both chronic and aggressive forms in the adult population. Outcomes included changes in attachment levels and/or deepening of periodontal pockets in millimeters in study populations undergoing supportive periodontal therapy.Data extraction and synthesisData extraction was performed independently and in collaboration by two reviewers; completed evidence tables were reviewed by three reviewers. Studies were each given a descriptive summary to assess the quantity of data as well as further assessment of study variations

  19. Progressive upper limb prosthetics.

    PubMed

    Lake, Chris; Dodson, Robert

    2006-02-01

    The field of upper extremity prosthetics is a constantly changing arena as researchers and prosthetists strive to bridge the gap between prosthetic reality and upper limb physiology. With the further development of implantable neurologic sensing devices and targeted muscle innervation (discussed elsewhere in this issue), the challenge of limited input to control vast outputs promises to become a historical footnote in the future annals of upper limb prosthetics. Soon multidextrous terminal devices, such as that found in the iLimb system(Touch EMAS, Inc., Edinburgh, UK), will be a clinical reality (Fig. 22). Successful prosthetic care depends on good communication and cooperation among the surgeon, the amputee, the rehabilitation team, and the scientists harnessing the power of technology to solve real-life challenges. If the progress to date is any indication, amputees of the future will find their dreams limited only by their imagination. PMID:16517345

  20. Progressive Familial Intrahepatic Cholestasis

    PubMed Central

    Srivastava, Anshu

    2013-01-01

    Progressive familial intrahepatic cholestasis (PFIC) is a group of rare disorders which are caused by defect in bile secretion and present with intrahepatic cholestasis, usually in infancy and childhood. These are autosomal recessive in inheritance. The estimated incidence is about 1 per 50,000 to 1 per 100,000 births, although exact prevalence is not known. These diseases affect both the genders equally and have been reported from all geographical areas. Based on clinical presentation, laboratory findings, liver histology and genetic defect, these are broadly divided into three types—PFIC type 1, PFIC type 2 and PFIC type 3. The defect is in ATP8B1 gene encoding the FIC1 protein, ABCB 11 gene encoding BSEP protein and ABCB4 gene encoding MDR3 protein in PFIC1, 2 and 3 respectively. The basic defect is impaired bile salt secretion in PFIC1/2 whereas in PFIC3, it is reduced biliary phospholipid secretion. The main clinical presentation is in the form of cholestatic jaundice and pruritus. Serum gamma glutamyl transpeptidase (GGT) is normal in patients with PFIC1/2 while it is raised in patients with PFIC3. Treatment includes nutritional support (adequate calories, supplementation of fat soluble vitamins and medium chain triglycerides) and use of medications to relieve pruritus as initial therapy followed by biliary diversion procedures in selected patients. Ultimately liver transplantation is needed in most patients as they develop progressive liver fibrosis, cirrhosis and end stage liver disease. Due to the high risk of developing liver tumors in PFIC2 patients, monitoring is recommended from infancy. Mutation targeted pharmacotherapy, gene therapy and hepatocyte transplantation are being explored as future therapeutic options. PMID:25755532