X inactivation in females with X-linked Charcot-Marie-Tooth disease.

LENUS (Irish Health Repository)

Murphy, Sinéad M

2012-07-01

X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X.

X-linked ichthyosis along with epidermolysis bullosa

Directory of Open Access Journals (Sweden)

Shambulingappa Pallagatti

2012-01-01

Full Text Available Ichthyoses are a heterogenous group of hereditary keratinization disorders that share in common the accumulation & shedding of large amounts of hyperkeratotic epidermis.Early reports of ichthyosis in the Indian and Chinese literature date back to several hundred years. X-linked recessive ichthyosis (XLI is a common disorder of keratinization and affects males who inherit an X-chromosome having a steroid sulphatase genetic mutation.In the present communication we report a case of XLI and dystrophic epidermolysis bullosa in the same patient. To the best of our knowledge it has been reported only once before.

Fine mapping of dominant X-linked incompatibility alleles in Drosophila hybrids.

Science.gov (United States)

Matute, Daniel R; Gavin-Smyth, Jackie

2014-04-01

Sex chromosomes have a large effect on reproductive isolation and play an important role in hybrid inviability. In Drosophila hybrids, X-linked genes have pronounced deleterious effects on fitness in male hybrids, which have only one X chromosome. Several studies have succeeded at locating and identifying recessive X-linked alleles involved in hybrid inviability. Nonetheless, the density of dominant X-linked alleles involved in interspecific hybrid viability remains largely unknown. In this report, we study the effects of a panel of small fragments of the D. melanogaster X-chromosome carried on the D. melanogaster Y-chromosome in three kinds of hybrid males: D. melanogaster/D. santomea, D. melanogaster/D. simulans and D. melanogaster/D. mauritiana. D. santomea and D. melanogaster diverged over 10 million years ago, while D. simulans (and D. mauritiana) diverged from D. melanogaster over 3 million years ago. We find that the X-chromosome from D. melanogaster carries dominant alleles that are lethal in mel/san, mel/sim, and mel/mau hybrids, and more of these alleles are revealed in the most divergent cross. We then compare these effects on hybrid viability with two D. melanogaster intraspecific crosses. Unlike the interspecific crosses, we found no X-linked alleles that cause lethality in intraspecific crosses. Our results reveal the existence of dominant alleles on the X-chromosome of D. melanogaster which cause lethality in three different interspecific hybrids. These alleles only cause inviability in hybrid males, yet have little effect in hybrid females. This suggests that X-linked elements that cause hybrid inviability in males might not do so in hybrid females due to differing sex chromosome interactions.

Bezafibrate for X-Linked Adrenoleukodystrophy

NARCIS (Netherlands)

Engelen, Marc; Tran, Luc; Ofman, Rob; Brennecke, Josephine; Moser, Ann B.; Dijkstra, Inge M. E.; Wanders, Ronald J. A.; Poll-The, Bwee Tien; Kemp, Stephan

2012-01-01

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene and is characterized by impaired beta-oxidation of very-long-chain fatty acids (VLCFA) and subsequent VLCFA accumulation in tissues. In adulthood X-ALD most commonly manifests as a gradually progressive myelopathy,

Accounting for eXentricities: analysis of the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases.

Directory of Open Access Journals (Sweden)

Diana Chang

Full Text Available Many complex human diseases are highly sexually dimorphic, suggesting a potential contribution of the X chromosome to disease risk. However, the X chromosome has been neglected or incorrectly analyzed in most genome-wide association studies (GWAS. We present tailored analytical methods and software that facilitate X-wide association studies (XWAS, which we further applied to reanalyze data from 16 GWAS of different autoimmune and related diseases (AID. We associated several X-linked genes with disease risk, among which (1 ARHGEF6 is associated with Crohn's disease and replicated in a study of ulcerative colitis, another inflammatory bowel disease (IBD. Indeed, ARHGEF6 interacts with a gastric bacterium that has been implicated in IBD. (2 CENPI is associated with three different AID, which is compelling in light of known associations with AID of autosomal genes encoding centromere proteins, as well as established autosomal evidence of pleiotropy between autoimmune diseases. (3 We replicated a previous association of FOXP3, a transcription factor that regulates T-cell development and function, with vitiligo; and (4 we discovered that C1GALT1C1 exhibits sex-specific effect on disease risk in both IBDs. These and other X-linked genes that we associated with AID tend to be highly expressed in tissues related to immune response, participate in major immune pathways, and display differential gene expression between males and females. Combined, the results demonstrate the importance of the X chromosome in autoimmunity, reveal the potential of extensive XWAS, even based on existing data, and provide the tools and incentive to properly include the X chromosome in future studies.

All-fiber 7x1 signal combiner for incoherent laser beam combining

DEFF Research Database (Denmark)

Noordegraaf, Danny; Maack, Martin D.; Skovgaard, Peter M. W.

2011-01-01

We demonstrate an all-fiber 7x1 signal combiner for incoherent laser beam combining. This is a potential key component for reaching several kW of stabile laser output power. The combiner couples the output from 7 single-mode (SM) fiber lasers into a single multi-mode (MM) fiber. The input signal ...... in device temperature is observed. At an intermediate power level of 600 W a beam parameter product (BPP) of 2.22 mm x mrad is measured, corresponding to an M2 value of 6.5. These values are approaching the theoretical limit dictated by brightness conservation....

Editorial: X-chromosome-linked Kallmann's syndrome: Pathology at the molecular level

Energy Technology Data Exchange (ETDEWEB)

Prager, D.; Braunstein, G.D. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))

1993-04-01

Kallmann's syndrome or olfactogenital dysplasia refers to a disorder characterized by hypogonadotropic hypogonadism and anosmia or hyposmia which can occur sporadically or in a familial setting. Originally described in 1856, the first familial cases were reported by Kallmann et al., in 1944. Based on segregation analysis of multiple families, three modes of transmission have been documented: X-linked, autosomal dominant with variable penetrance, and autosomal recessive. Kallmann's syndrome occurs in less than 1 in 10,000 male births, with a 5-fold excess of affected males to females, suggesting that the X-linked form is the most frequent. By genetic linkage analysis the X-linked form of Kallmann's syndrome was localized to Xp22.3. This was confirmed by the description of patients with contiguous gene syndromes due to deletions of various portions of the distal short arm of the X-chromosome. Such patients present with complex phenotypes characterized by a combination of Kallmann's syndrome with X-linked icthyosis due to steroid sulfatase deficiency, chondrodysplasia punctata, short stature, and mental retardation. DNA analysis has identified and mapped the genes responsible for these disorders. 10 refs., 1 fig., 1 tab.

A complex genetic basis to X-linked hybrid male sterility between two species of house mice.

Science.gov (United States)

Good, Jeffrey M; Dean, Matthew D; Nachman, Michael W

2008-08-01

The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome.

X-linked hypophosphatemic rickets without 'rickets'

Energy Technology Data Exchange (ETDEWEB)

Econs, M.J.; Feussner, J.R.; Quarles, L.D. (Duke Univ. Medical Center, Durham, NC (USA). Dept. of Medicine Veterans Administration Medical Center, Durham, NC (USA). Health Services Research Field Program); Samsa, G.P. (Duke Univ. Medical Center, Durham, NC (USA). Dept. of Biometry Veterans Administration Medical Center, Durham, NC (USA). Health Services Research Field Program); Effman, E.L.; Vogler, J.B.; Martinez, S. (Duke Univ. Medical Center, Durham, NC (USA). Dept. of Radiology Veterans Administration Medical Center, Durham, NC (USA). Health Services Research Field Program); Friedman, N.E. (Duke Univ. Medical Center, Durham, NC (USA). Dept. of Pediatrics Veterans Administration Medical Center, Durham, NC (USA). Health Services Research Field Program); Drezner, M.K. (Duke Univ. Medical Center, Durham, NC (USA). Dept. of Medicine Duke Univ. Medical Center, Durham, NC (USA). Dept. of Cell Biology Veterans Administration Medical Center, Durham, NC (USA). Health Services Research F

1991-02-01

Wrist and knee radiographs from children with X-linked hypophosphatemic rickets were analyzed and compared with those from normal children and children with established rickets to assess whether radiographically apparent rickets is a consistent abnormality in X-linked hypophosphatemia. The absence or presence of rickets was correctly identified in 94.8% of wrist and knee films from normal and positive controls. In contrast, patients with X-linked hypophosphatemia exhibited rachitic abnormalities in only 5 of 11 wrist and 13 of 15 knee radiographs. Our data indicate that radiographically detectable rickets is a variable abnormality of X-linked hypophosphatemia and does not provide an unambiguous index for the diagnosis of this disease. (orig./GDG).

X-linked inhibitor of apoptosis (XIAP) deficiency

DEFF Research Database (Denmark)

Speckmann, C.; Lehmberg, K.; Albert, M.H.

2013-01-01

X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant...

Pyoderma Gangrenosum–Like Ulcer in a Patient With X-Linked Agammaglobulinemia

Science.gov (United States)

Murray, Patrick R.; Jain, Ashish; Uzel, Gulbu; Ranken, Raymond; Ivy, Cristina; Blyn, Lawrence B.; Ecker, David J.; Sampath, Rangarajan; Lee, Chyi-Chia Richard; Turner, Maria L.

2011-01-01

Background Pyoderma gangrenosum–like ulcers and cellulitis of the lower extremities associated with recurrent fevers in patients with X-linked (Bruton) agammaglobulinemia have been reported to be caused by Helicobacter bilis (formerly classified as Flexispira rappini and then Helicobacter strain flexispira taxon 8). Consistent themes in these reports are the difficulty in recovering this organism in blood and wound cultures and in maintaining isolates in vitro. We confirmed the presence of this organism in a patient’s culture by using a novel application of gene amplification polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry. Observation An adolescent boy with X-linked agammaglobulinemia presented with indurated plaques and a chronic leg ulcer whose origin was strongly suspected to be an H bilis organism. Histologic analysis demonstrated positive Warthin-Starry staining of curvilinear rods, which grew in culture but failed to grow when sub-cultured. They could not be identified by conventional techniques. A combination of gene amplification by polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry confirmed the identity of this organism. Conclusions This novel technology was useful in the identification of a difficult-to-grow Helicobacter organism, the cause of pyoderma gangrenosum–like leg ulcers in patients with X-linked agammaglobulinemia. Correct identification of this organism as the cause of pyoderma gangrenosum–like ulcers in patients with X-linked agammaglobulinemia is of great importance for the early initiation of appropriate and curative antibiotic therapy. PMID:20479300

Genetics Home Reference: X-linked sideroblastic anemia and ataxia

Science.gov (United States)

... linked sideroblastic anemia and ataxia X-linked sideroblastic anemia and ataxia Printable PDF Open All Close All ... the expand/collapse boxes. Description X-linked sideroblastic anemia and ataxia is a rare condition characterized by ...

A novel mutation in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene associated with a severe Rett phenotype.

Science.gov (United States)

Sprovieri, T; Conforti, F L; Fiumara, A; Mazzei, R; Ungaro, C; Citrigno, L; Muglia, M; Arena, A; Quattrone, A

2009-02-15

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have recently been reported in patients with severe neurodevelopmental disorder characterized by early-onset seizures, infantile spasms, severe psychomotor impairment and very recently, in patients with Rett syndrome (RTT)-like phenotype. Although the involvement of CDKL5 in specific biological pathways and its neurodevelopmental role have not been completely elucidated, the CDKL5 appears to be physiologically related to the MECP2 gene. Here we report on the clinical and CDKL5 molecular investigation in a very unusual RTT case, with severe, early-neurological involvement in which we have shown in a previous report, a novel P388S MECP2 mutation [Conforti et al. (2003); Am J Med Genet A 117A: 184-187]. The patient has had severe psychomotor delay since the first month of life and infantile spasms since age 5 months. Moreover, at age 5 years the patient suddenly presented with renal failure. The severe pattern of symptoms in our patient, similar to a CDKL5 phenotype, prompted us to perform an analysis of the CDKL5, which revealed a novel missense mutation never previously described. The X-inactivation assay was non-informative. In conclusion, this report reinforces the observation that the CDKL5 phenotype overlaps with RTT and that CDKL5 analysis is recommended in patients with a seizure disorder commencing during the first months of life.

Genetics Home Reference: alpha thalassemia X-linked intellectual disability syndrome

Science.gov (United States)

... Alpha thalassemia X-linked intellectual disability syndrome Alpha thalassemia X-linked intellectual disability syndrome Printable PDF Open ... to view the expand/collapse boxes. Description Alpha thalassemia X-linked intellectual disability syndrome is an inherited ...

Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy: a retrospective study

NARCIS (Netherlands)

Assies, J.; Gooren, L. J.; van Geel, B.; Barth, P. G.

1997-01-01

X-linked adrenoleukodystrophy (X-ALD) is characterized by central nervous system demyelination, and impaired steroidogenesis in the adrenal cortex and testis. Most patients develop adrenocortical insufficiency. We studied retrospectively the frequency and severity of testicular dysfunction in 26 men

All-fiber 7x1 signal combiner for incoherent laser beam combining

Science.gov (United States)

Noordegraaf, D.; Maack, M. D.; Skovgaard, P. M. W.; Johansen, J.; Becker, F.; Belke, S.; Blomqvist, M.; Laegsgaard, J.

2011-02-01

We demonstrate an all-fiber 7x1 signal combiner for incoherent laser beam combining. This is a potential key component for reaching several kW of stabile laser output power. The combiner couples the output from 7 single-mode (SM) fiber lasers into a single multi-mode (MM) fiber. The input signal fibers have a core diameter of 17 μm and the output MM fiber has a core diameter of 100 μm. In a tapered section light gradually leaks out of the SM fibers and is captured by a surrounding fluorine-doped cladding. The combiner is tested up to 2.5 kW of combined output power and only a minor increase in device temperature is observed. At an intermediate power level of 600 W a beam parameter product (BPP) of 2.22 mm x mrad is measured, corresponding to an M2 value of 6.5. These values are approaching the theoretical limit dictated by brightness conservation.

X-linked congenital panhypopituitarism.

Science.gov (United States)

Schimke, R N; Spaulding, J J; Hollowell, J G

1971-05-01

Two half brothers with panhypopituitary dwarfism are reported who have the same mother and different, unrelated fathers. The subject of hereditary panhypopituitarism is reviewed briefly. It is concluded that there are at least two forms of hereditary panhypopituitary dwarfism, one of which may be X-linked.

A family with X-linked anophthalmia: exclusion of SOX3 as a candidate gene.

Science.gov (United States)

Slavotinek, Anne; Lee, Stephen S; Hamilton, Steven P

2005-10-01

We report on a four-generation family with X-linked anophthalmia in four affected males and show that this family has LOD scores consistent with linkage to Xq27, the third family reported to be linked to the ANOP1 locus. We sequenced the SOX3 gene at Xq27 as a candidate gene for the X-linked anophthalmia based on the high homology of this gene to SOX2, a gene previously mutated in bilateral anophthlamia. However, no amino acid sequence alterations were identified in SOX3. We have improved the definition of the phenotype in males with anophthalmia linked to the ANOP1 locus, as microcephaly, ocular colobomas, and severe renal malformations have not been described in families linked to ANOP1. (c) 2005 Wiley-Liss, Inc.

7 Tesla proton magnetic resonance spectroscopic imaging in adult X-linked adrenoleukodystrophy

Science.gov (United States)

Ratai, Eva; Kok, Trina; Wiggins, Christopher; Wiggins, Graham; Grant, Ellen; Gagoski, Borjan; O'Neill, Gilmore; Adalsteinsson, Elfar; Eichler, Florian

2010-01-01

Background Adult patients with X-linked adrenoleukodystrophy (X-ALD) remain at risk for progressive neurological deterioration. Phenotypes vary in their pathology, ranging from axonal degeneration to inflammatory demyelination. The severity of symptoms is poorly explained by conventional imaging. Objective To test the hypothesis that neurochemistry in normal appearing brain differs among adult phenotypes of X-ALD, and that neurochemical changes correlate with the severity of symptoms. Patients and Methods Using a 7 Tesla scanner we performed structural and proton MRSI in 13 adult patients with X-ALD, including 4 patients with adult cerebral ALD (ACALD), 5 with adrenomyeloneuropathy (AMN) and 4 female heterozygotes. Studies were also performed in nine healthy controls. Results Among adult X-ALD phenotypes, MI/Cr was 46% higher and Cho/Cr 21% higher in normal appearing white matter of ACALD compared to AMN (p Tesla proton MRSI reveals differences in the neurochemistry of ACALD but is unable to distinguish AMN from female heterozygotes. MI/Cr correlates with the severity of the symptoms and may be a meaningful biomarker in adult X-ALD. PMID:19001168

X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

Science.gov (United States)

Fullwood, P; Jones, J; Bundey, S; Dudgeon, J; Fielder, A R; Kilpatrick, M W

1993-03-01

A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

X-linked Alport syndrome

DEFF Research Database (Denmark)

Jais, J P; Knebelmann, B; Giatras, I

2000-01-01

Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease....... Considerable allelic heterogeneity has been observed. A "European Community Alport Syndrome Concerted Action" has been established to delineate accurately the AS phenotype and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X...

Genetics Home Reference: X-linked intellectual disability, Siderius type

Science.gov (United States)

... Cleft Lip and Palate MalaCards: x-linked intellectual disability, siderius type March of Dimes: Cleft Lip and Cleft Palate Merck Manual Consumer Version: Intellectual Disability Orphanet: X-linked intellectual disability, Siderius type Patient ...

A Comparison of Selective Pressures in Plant X-Linked and Autosomal Genes.

Science.gov (United States)

Krasovec, Marc; Nevado, Bruno; Filatov, Dmitry A

2018-05-03

Selection is expected to work differently in autosomal and X-linked genes because of their ploidy difference and the exposure of recessive X-linked mutations to haploid selection in males. However, it is not clear whether these expectations apply to recently evolved sex chromosomes, where many genes retain functional X- and Y-linked gametologs. We took advantage of the recently evolved sex chromosomes in the plant Silene latifolia and its closely related species to compare the selective pressures between hemizygous and non-hemizygous X-linked genes as well as between X-linked genes and autosomal genes. Our analysis, based on over 1000 genes, demonstrated that, similar to animals, X-linked genes in Silene evolve significantly faster than autosomal genes—the so-called faster-X effect. Contrary to expectations, faster-X divergence was detectable only for non-hemizygous X-linked genes. Our phylogeny-based analyses of selection revealed no evidence for faster adaptation in X-linked genes compared to autosomal genes. On the other hand, partial relaxation of purifying selection was apparent on the X-chromosome compared to the autosomes, consistent with a smaller genetic diversity in S. latifolia X-linked genes (π x = 0.016; π aut = 0.023). Thus, the faster-X divergence in S. latifolia appears to be a consequence of the smaller effective population size rather than of a faster adaptive evolution on the X-chromosome. We argue that this may be a general feature of “young” sex chromosomes, where the majority of X-linked genes are not hemizygous, preventing haploid selection in heterogametic sex.

X-linked cataract and Nance-Horan syndrome are allelic disorders.

Science.gov (United States)

Coccia, Margherita; Brooks, Simon P; Webb, Tom R; Christodoulou, Katja; Wozniak, Izabella O; Murday, Victoria; Balicki, Martha; Yee, Harris A; Wangensteen, Teresia; Riise, Ruth; Saggar, Anand K; Park, Soo-Mi; Kanuga, Naheed; Francis, Peter J; Maher, Eamonn R; Moore, Anthony T; Russell-Eggitt, Isabelle M; Hardcastle, Alison J

2009-07-15

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication-triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved.

A puzzling combination: disorder X order

International Nuclear Information System (INIS)

Hasenfratz, P.

1979-01-01

There are several examples indicating that the operator combination 'disorder X order' creates anomalous spin and/or statistics. In 2 + 1 dimensions there is a similar anomaly related to the disorder operator carrying Z(N) topological charge believed to have an important role in quark confinement. The conventionally defined total angular momentum has an anomalous term 1/2 sigma 3 ((1/√3) lambda 8 ) and can take the values 1/2 (1/3) in the presence of 'disorder X order' in 2 + 1 dimensional SU(2) (SU(3)) gauge theories. It is argued that the existence of a stable soliton solution or the introduction of Higgs fields are not important for the anomaly. (Auth.)

A new nonsyndromic X-linked sensorineural hearing impairment linked to Xp21.2

Energy Technology Data Exchange (ETDEWEB)

Lalwani, A.K.; Brister, J.R.; Fex, J.; Grundfast, K.M.; Pikus, A.T.; Ploplis, B.; San Agustin, T.; Skarka, H.; Wilcox, E.R. [National Institutes of Health, Bethesda, MD (United States)

1994-10-01

X-linked deafness is a rare cause of hereditary hearing impairment. We have identified a family with X-linked dominant sensorineural hearing impairment, characterized by incomplete penetrance and variable expressivity in carrier females, that is linked to the Xp21.2, which contains the Duchenne muscular dystrophy (DMD) locus. The auditory impairment in affected males was congenital, bilateral, profound, sensorineural, affecting all frequencies, and without evidence of radiographic abnormality of the temporal bone. Adult carrier females manifested bilateral, mild-to-moderate high-frequency sensorineural hearing impairment of delayed onset during adulthood. Eighteen commercially available polymorphic markers from the X chromosome, generating a 10-15-cM map, were initially used for identification of a candidate region. DXS997, located within the DMD gene, generated a two-point LOD score of 2.91 at {theta} = 0, with every carrier mother heterozygous at this locus. Recombination events at DXS992 (located within the DMD locus, 3{prime} to exon 50 of the dystrophin gene) and at DXS1068 (5{prime} to the brain promoter of the dystrophin gene) were observed. No recombination events were noted with the following markers within the DMD locus: 5{prime}DYS II, intron 44, DXS997, and intron 50. There was no clinical evidence of Duchenne or Becker muscular dystrophy in any family member. It is likely that this family represents a new locus on the X chromosome, which when mutated results in nonsyndromic sensorineural hearing loss and is distinct from the heterogeneous group of X-linked hearing losses that have been previously described. 57 refs., 6 figs., 1 tab.

X-linked Acrogigantism (X-LAG) Syndrome: Clinical Profile and Therapeutic Responses

OpenAIRE

Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick

2015-01-01

X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the...

Alpha thalassaemia-mental retardation, X linked

Directory of Open Access Journals (Sweden)

Gibbons Richard

2006-05-01

Full Text Available Abstract X-linked alpha thalassaemia mental retardation (ATR-X syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal. So far, 168 patients have been reported. Language is usually very limited. Seizures occur in about one third of the cases. While many patients are affectionate with their caregivers, some exhibit autistic-like behaviour. Patients present with facial hypotonia and a characteristic mouth. Genital abnormalities are observed in 80% of children and range from undescended testes to ambiguous genitalia. Alpha-thalassaemia is not always present. This syndrome is X-linked recessive and results from mutations in the ATRX gene. This gene encodes the widely expressed ATRX protein. ATRX mutations cause diverse changes in the pattern of DNA methylation at heterochromatic loci but it is not yet known whether this is responsible for the clinical phenotype. The diagnosis can be established by detection of alpha thalassaemia, identification of ATRX gene mutations, ATRX protein studies and X-inactivation studies. Genetic counselling can be offered to families. Management is multidisciplinary: young children must be carefully monitored for gastro-oesophageal reflux as it may cause death. A number of individuals with ATR-X are fit and well in their 30s and 40s.

X-linked Acrogigantism (X-LAG) Syndrome: Clinical Profile and Therapeutic Responses

Science.gov (United States)

Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J.; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H.; Bours, Vincent; Liu, Pengfei; De Herder, Wouter; Pellegata, Natalia; Lupski, James R.; Daly, Adrian F.; Stratakis, Constantine A.

2015-01-01

X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF-1 and prolactin, usually due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high somatostatin receptor subtype-2 expression in tumor tissue. Postoperative adjuvant pegvisomant achieved control of IGF-1 all 5 cases in which it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. PMID:25712922

Genetics Home Reference: X-linked thrombocytopenia

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... Benson EM. Identification of WASP mutations in 10 Australian families with Wiskott-Aldrich syndrome and X-linked ... API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & Players U.S. Department of ...

Molecular and Clinical Studies of X-linked Deafness Among Pakistani Families

OpenAIRE

Waryah, Ali M.; Ahmed, Zubair M.; Choo, Daniel I.; Sisk, Robert A.; Binder, Munir A.; Shahzad, Mohsin; Khan, Shaheen N.; Friedman, Thomas B.; Riazuddin, Sheikh; Riazuddin, Saima

2011-01-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132, PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively....

Frequency of CNKSR2 mutation in the X-linked epilepsy-aphasia spectrum.

Science.gov (United States)

Damiano, John A; Burgess, Rosemary; Kivity, Sara; Lerman-Sagie, Tally; Afawi, Zaid; Scheffer, Ingrid E; Berkovic, Samuel F; Hildebrand, Michael S

2017-03-01

Synaptic proteins are critical to neuronal function in the brain, and their deficiency can lead to seizures and cognitive impairments. CNKSR2 (connector enhancer of KSR2) is a synaptic protein involved in Ras signaling-mediated neuronal proliferation, migration and differentiation. Mutations in the X-linked gene CNKSR2 have been described in patients with seizures and neurodevelopmental deficits, especially those affecting language. In this study, we sequenced 112 patients with phenotypes within the epilepsy-aphasia spectrum (EAS) to determine the frequency of CNKSR2 mutation within this complex set of disorders. We detected a novel nonsense mutation (c.2314 C>T; p.Arg712*) in one Ashkenazi Jewish family, the male proband of which had a severe epileptic encephalopathy with continuous spike-waves in sleep (ECSWS). His affected brother also had ECSWS with better outcome, whereas the sister had childhood epilepsy with centrotemporal spikes. This mutation segregated in the three affected siblings in an X-linked manner, inherited from their mother who had febrile seizures. Although the frequency of point mutation is low, CNKSR2 sequencing should be considered in families with suspected X-linked EAS because of the specific genetic counseling implications. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

A new resource for characterizing X-linked genes in Drosophila melanogaster: systematic coverage and subdivision of the X chromosome with nested, Y-linked duplications.

Science.gov (United States)

Cook, R Kimberley; Deal, Megan E; Deal, Jennifer A; Garton, Russell D; Brown, C Adam; Ward, Megan E; Andrade, Rachel S; Spana, Eric P; Kaufman, Thomas C; Cook, Kevin R

2010-12-01

Interchromosomal duplications are especially important for the study of X-linked genes. Males inheriting a mutation in a vital X-linked gene cannot survive unless there is a wild-type copy of the gene duplicated elsewhere in the genome. Rescuing the lethality of an X-linked mutation with a duplication allows the mutation to be used experimentally in complementation tests and other genetic crosses and it maps the mutated gene to a defined chromosomal region. Duplications can also be used to screen for dosage-dependent enhancers and suppressors of mutant phenotypes as a way to identify genes involved in the same biological process. We describe an ongoing project in Drosophila melanogaster to generate comprehensive coverage and extensive breakpoint subdivision of the X chromosome with megabase-scale X segments borne on Y chromosomes. The in vivo method involves the creation of X inversions on attached-XY chromosomes by FLP-FRT site-specific recombination technology followed by irradiation to induce large internal X deletions. The resulting chromosomes consist of the X tip, a medial X segment placed near the tip by an inversion, and a full Y. A nested set of medial duplicated segments is derived from each inversion precursor. We have constructed a set of inversions on attached-XY chromosomes that enable us to isolate nested duplicated segments from all X regions. To date, our screens have provided a minimum of 78% X coverage with duplication breakpoints spaced a median of nine genes apart. These duplication chromosomes will be valuable resources for rescuing and mapping X-linked mutations and identifying dosage-dependent modifiers of mutant phenotypes.

Genetics Home Reference: X-linked spondyloepiphyseal dysplasia tarda

Science.gov (United States)

... Educational Resources (6 links) Cincinnati Children's Hospital: Coxa Vera Disease InfoSearch: Spondyloepiphyseal dysplasia tarda X-linked Johns ... Free article on PubMed Central Savarirayan R, Thompson E, Gécz J. Spondyloepiphyseal dysplasia tarda (SEDL, MIM #313400). ...

Mapping of the X-linked cataract (Xcat) mutation, the gene implicated in the Nance Horan syndrome, on the mouse X chromosome.

Science.gov (United States)

Stambolian, D; Favor, J; Silvers, W; Avner, P; Chapman, V; Zhou, E

1994-07-15

The Xcat mutation in the mouse, an X-linked inherited disorder, is characterized by the congenital onset of cataracts. The cataracts have morphologies similar to those of cataracts found in the human Nance Horan (X-linked cataract dental) syndrome, suggesting that Xcat is an animal model for Nance Horan. The Xcat mutation provides an opportunity to investigate, at the molecular level, the pathogenesis of cataract. As a first step to cloning the Xcat gene, we report the localization of the Xcat mutation with respect to known molecular markers on the mouse X chromosome. Back-cross progeny carrying the Xcat mutation were obtained from an interspecific cross. Genomic DNA from each mouse was subjected to Southern and PCR analysis to identify restriction fragment length polymorphisms and simple sequence length polymorphisms, respectively. Our results refine the location of Xcat to a 2-cM region, eliminate several genes from consideration as the Xcat mutation, identify molecular probes tightly linked with Xcat, and suggest candidate genes responsible for the Xcat phenotype.

Guillain Barré Syndrome in a Child With X-Linked Adrenoleukodystrophy

Directory of Open Access Journals (Sweden)

Ron Jacob MD

2015-10-01

Full Text Available X-Linked adrenoleukodystrophy is the most common peroxisomal disorder with different phenotypes among patients carrying the same ABCD1 mutation. There were previously reported associations of X-linked adrenoleukodystrophy with autoimmune disorders. The authors describe Guillain Barré syndrome in a child with X-linked adrenoleukodystrophy. The available evidence does not permit conclusion concerning etiological linkage between the 2 diseases, but it warrants further study.

X-linked ichthyosis associated with psychosis and behavioral abnormalities: a case report.

Science.gov (United States)

Malik, Amna; Amer, Ahmed Bait; Salama, Mohammed; Haddad, Bander; Alrifai, Muhammad T; Balwi, Mohammed Al; Davies, William; Eyaid, Wafaa

2017-09-22

X-linked ichthyosis is a dermatological condition caused by deficiency for the enzyme steroid sulfatase. Previously, X-linked ichthyosis/steroid sulfatase deficiency has been associated with developmental and neurological phenotypes. Here, we show for the first time, that X-linked ichthyosis may be comorbid with an additional psychiatric phenotype (psychosis). We report the case of an 11-year-old Saudi Arabian boy with X-linked ichthyosis associated with psychosis, mental retardation, autism spectrum disorder, inattentive attention deficit hyperactivity disorder, and epilepsy. Genetic analysis revealed a 1.68 Mb deletion encompassing STS in 95% of cells while biochemical analysis revealed correspondingly low steroid sulfatase activity consistent with a diagnosis of X-linked ichthyosis. The psychotic symptoms could be reasonably well controlled by administration of an atypical antipsychotic. This report describes a case of comorbid X-linked ichthyosis and psychosis (most closely corresponding to early-onset schizophrenia) for the first time, and suggests that deficiency for steroid sulfatase and contiguous genes may increase vulnerability to psychosis as well as other psychological disorders.

A novel UBE2A mutation causes X-linked intellectual disability type Nascimento.

Science.gov (United States)

Tsurusaki, Yoshinori; Ohashi, Ikuko; Enomoto, Yumi; Naruto, Takuya; Mitsui, Jun; Aida, Noriko; Kurosawa, Kenji

2017-01-01

X-linked intellectual disability (ID) type Nascimento (MIM #300860), also known as ubiquitin-conjugating enzyme E2 A (UBE2A) deficiency syndrome, is a congenital malformation syndrome characterized by moderate to severe ID, speech impairment, dysmorphic facial features, genital anomalies and skin abnormalities. Here, we report a Japanese patient with severe ID and congenital cataract. We identified a novel hemizygous mutation (c.76G>A, p.Gly26Arg) in UBE2A by whole-exome sequencing.

Molecular and Clinical Studies of X-linked Deafness Among Pakistani Families

Science.gov (United States)

Waryah, Ali M.; Ahmed, Zubair M.; Choo, Daniel I.; Sisk, Robert A.; Binder, Munir A.; Shahzad, Mohsin; Khan, Shaheen N.; Friedman, Thomas B.; Riazuddin, Sheikh; Riazuddin, Saima

2011-01-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132, PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild to profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling, and molecular epidemiology of hearing loss among Pakistanis. PMID:21633365

Molecular and clinical studies of X-linked deafness among Pakistani families.

Science.gov (United States)

Waryah, Ali M; Ahmed, Zubair M; Bhinder, Munir A; Binder, Munir A; Choo, Daniel I; Sisk, Robert A; Shahzad, Mohsin; Khan, Shaheen N; Friedman, Thomas B; Riazuddin, Sheikh; Riazuddin, Saima

2011-07-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis.

Possible X linked congenital mitochondrial cardiomyopathy in three families.

OpenAIRE

Orstavik, K H; Skjörten, F; Hellebostad, M; Hågå, P; Langslet, A

1993-01-01

Familial cases of childhood congestive cardiomyopathy with X linked recessive inheritance and abnormalities of heart muscle mitochondria have been previously reported. We report here three families with possible X linked congestive cardiomyopathy and specific mitochondrial abnormalities. The heart disorder presented as endocardial fibroelastosis with neonatal death in two brothers in one family, and as heart failure and death in infancy in two brothers in the other two families. In one family...

Genetics Home Reference: severe congenital neutropenia

Science.gov (United States)

... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... Genetic Testing Registry: Severe congenital neutropenia 2, autosomal dominant Genetic Testing Registry: Severe congenital neutropenia 3, autosomal ...

X-linked deafness with stapes gusher in females

International Nuclear Information System (INIS)

Papadaki, E.; Prassopoulos, P.; Bizakis, J.; Karampekios, S.; Papadakis, H.; Gourtsoyiannis, N.

1998-01-01

A 22-year-old woman presented with severe mixed hearing loss and a flow of cerebrospinal fluid in the middle ear during stapes surgery (stapes gusher). HRCT of the temporal bones showed characteristic abnormalities of the inner ear (bulbous dilatation of the lateral portion of the internal acoustic meatus with incomplete separation from the cochlea, and widening of the first part of the facial nerve canal) described in X-linked progressive mixed deafness with stapes gusher. The evaluation of the patient's family revealed a sister with the same clinical history and identical HRCT findings, and 11 normal male relatives. This is the first report with typical findings of this entity that affects only female members of a family, suggesting another type of inheritance

Genetics Home Reference: X-linked juvenile retinoschisis

Science.gov (United States)

... in a decrease in or complete loss of functional retinoschisin, which disrupts the maintenance and organization of ... sides of the retina, resulting in impaired peripheral vision. Some individuals with X-linked juvenile retinoschisis do ...

Screening for X-linked adrenoleukodystrophy among adult men with Addison's disease.

Science.gov (United States)

Horn, Morten A; Erichsen, Martina M; Wolff, Anette S B; Månsson, Jan-Eric; Husebye, Eystein S; Tallaksen, Chantal M E; Skjeldal, Ola H

2013-09-01

X-linked adrenoleukodystrophy is an important cause of Addison's disease in boys, but less is known about its contribution to Addison's disease in adult men. After surveying all known cases of X-linked adrenoleukodystrophy in Norway in a separate study, we aimed to look for any missed cases among the population of adult men with nonautoimmune Addison's disease. Among 153 adult men identified in a National Registry for Addison's Disease (75% of identified male cases of Addison's disease in Norway), those with negative indices for 21-hydroxylase autoantibodies were selected. Additionally, cases with low autoantibody indices (48-200) were selected. Sera from subjects included were analysed for levels of very long-chain fatty acids, which are diagnostic for X-linked adrenoleukodystrophy in men. Eighteen subjects had negative indices and 17 had low indices for 21-hydroxylase autoantibodies. None of those with low indices and only one of those with negative indices were found to have X-linked adrenoleukodystrophy; this subject had already been diagnosed because of the neurological symptoms. Cases of Addison's disease proved to be caused by X-linked adrenoleukodystrophy constitute 1·5% of all adult male cases in Norway; the proportion among nonautoimmune cases was 15%. We found X-linked adrenoleukodystrophy to be an uncommon cause of Addison's disease in adult men. However, this aetiological diagnosis has far-reaching consequences both for the patient and for his extended family. We therefore recommend that all adult men with nonautoimmune Addison's disease be analysed for levels of very long-chain fatty acids. © 2013 John Wiley & Sons Ltd.

X-linked retinoschisis: RS1 mutation severity and age affect the ERG phenotype in a cohort of 68 affected male subjects.

Science.gov (United States)

Bowles, Kristen; Cukras, Catherine; Turriff, Amy; Sergeev, Yuri; Vitale, Susan; Bush, Ronald A; Sieving, Paul A

2011-11-29

To assess the effect of age and RS1 mutation on the phenotype of X-linked retinoschisis (XLRS) subjects using the clinical electroretinogram (ERG) in a cross-sectional analysis. Sixty-eight XLRS males 4.5 to 55 years of age underwent genotyping, and the retinoschisis (RS1) mutations were classified as less severe (27 subjects) or more severe (41 subjects) based on the putative impact on the protein. ERG parameters of retinal function were analyzed by putative mutation severity with age as a continuous variable. The a-wave amplitude remained greater than the lower limit of normal (mean, -2 SD) for 72% of XLRS males and correlated with neither age nor mutation class. However, b-wave and b/a-ratio amplitudes were significantly lower in the more severe than in the less severe mutation groups and in older than in younger subjects. Subjects up to 10 years of age with more severe RS1 mutations had significantly greater b-wave amplitudes and faster a-wave trough implicit times than older subjects in this group. RS1 mutation putative severity and age both had significant effects on retinal function in XLRS only in the severe mutation group, as judged by ERG analysis of the b-wave amplitude and the b/a-ratio, whereas the a-wave amplitude remained normal in most. A new observation was that increasing age (limited to those aged 55 and younger) caused a significant delay in XLRS b-wave onset (i.e., a-wave implicit time), even for those who retained considerable b-wave amplitudes. The delayed b-wave onset suggested that dysfunction of the photoreceptor synapse or of bipolar cells increases with age of XLRS subjects.

MULTIMODAL IMAGING OF MOSAIC RETINOPATHY IN CARRIERS OF HEREDITARY X-LINKED RECESSIVE DISEASES.

Science.gov (United States)

Wu, An-Lun; Wang, Jung-Pan; Tseng, Yun-Ju; Liu, Laura; Kang, Yu-Chuan; Chen, Kuan-Jen; Chao, An-Ning; Yeh, Lung-Kun; Chen, Tun-Lu; Hwang, Yih-Shiou; Wu, Wei-Chi; Lai, Chi-Chun; Wang, Nan-Kai

2018-05-01

To investigate the clinical features in carriers of X-linked retinitis pigmentosa, X-linked ocular albinism, and choroideremia (CHM) using multimodal imaging and to assess their diagnostic value in these three mosaic retinopathies. We prospectively examined 14 carriers of 3 X-linked recessive disorders (X-linked retinitis pigmentosa, X-linked ocular albinism, and CHM). Details of abnormalities of retinal morphology were evaluated using fundus photography, fundus autofluorescence (FAF) imaging, and spectral domain optical coherence tomography. In six X-linked retinitis pigmentosa carriers, fundus appearance varied from unremarkable to the presence of tapetal-like reflex and pigmentary changes. On FAF imaging, all carriers exhibited a bright radial reflex against a dark background. By spectral domain optical coherence tomography, loss of the ellipsoid zone in the macula was observed in 3 carriers (50%). Regarding the retinal laminar architecture, 4 carriers (66.7%) showed thinning of the outer nuclear layer and a dentate appearance of the outer plexiform layer. All five X-linked ocular albinism carriers showed a characteristic mud-splatter patterned fundus, dark radial streaks against a bright background on FAF imaging, and a normal-appearing retinal structure by spectral domain optical coherence tomography imaging. Two of the 3 CHM carriers (66.7%) showed a diffuse moth-eaten appearance of the fundus, and all 3 showed irregular hyper-FAF and hypo-FAF spots throughout the affected area. In the CHM carriers, the structural changes observed by spectral domain optical coherence tomography imaging were variable. Our findings in an Asian cohort suggest that FAF imaging is a practical diagnostic test for differentiating X-linked retinitis pigmentosa, X-linked ocular albinism, and CHM carriers. Wide-field FAF is an easy and helpful adjunct to testing for the correct diagnosis and identification of lyonization in carriers of these three mosaic retinopathies.

Combined optic system based on polycapillary X-ray optics and single-bounce monocapillary optics for focusing X-rays from a conventional laboratory X-ray source

Energy Technology Data Exchange (ETDEWEB)

Sun, Xuepeng; Liu, Zhiguo [The Key Laboratory of Beam Technology and Materials Modification of the Ministry of Education, Beijing Normal University, Beijing 100875 (China); College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); Sun, Tianxi, E-mail: stx@bnu.edu.cn [The Key Laboratory of Beam Technology and Materials Modification of the Ministry of Education, Beijing Normal University, Beijing 100875 (China); College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); Yi, Longtao; Sun, Weiyuan; Li, Fangzuo; Jiang, Bowen [The Key Laboratory of Beam Technology and Materials Modification of the Ministry of Education, Beijing Normal University, Beijing 100875 (China); College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); Ma, Yongzhong [Center for Disease Control and Prevention of Beijing, Beijing 100013 (China); Ding, Xunliang [The Key Laboratory of Beam Technology and Materials Modification of the Ministry of Education, Beijing Normal University, Beijing 100875 (China); College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China)

2015-12-01

Two combined optic systems based on polycapillary X-ray optics and single-bounce monocapillary optics (SBMO) were designed for focusing the X-rays from a conventional laboratory X-ray source. One was based on a polycapillary focusing X-ray lens (PFXRL) and a single-bounce ellipsoidal capillary (SBEC), in which the output focal spot with the size of tens of micrometers of the PFXRL was used as the “virtual” X-ray source for the SBEC. The other system was based on a polycapillary parallel X-ray lens (PPXRL) and a single-bounce parabolic capillary (SBPC), in which the PPXRL transformed the divergent X-ray beam from an X-ray source into a quasi-parallel X-ray beam with the divergence of sever milliradians as the incident illumination of the SBPC. The experiment results showed that the combined optic systems based on PFXRL and SBEC with a Mo rotating anode X-ray generator with the focal spot with a diameter of 300 μm could obtain a focal spot with the total gain of 14,300 and focal spot size of 37.4 μm, and the combined optic systems based on PPXRL and SBPC with the same X-ray source mentioned above could acquire a focal spot with the total gain of 580 and focal spot size of 58.3 μm, respectively. The two combined optic systems have potential applications in micro X-ray diffraction, micro X-ray fluorescence, micro X-ray absorption near edge structure, full field X-ray microscopes and so on.

Genetics Home Reference: X-linked lymphoproliferative disease

Science.gov (United States)

... my area? Other Names for This Condition Duncan disease Epstein-Barr virus-induced lymphoproliferative disease in males familial fatal ... the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development. ...

Refinement of the localization of the X-linked ocular albinism gene

NARCIS (Netherlands)

Bergen, A. A.; Zijp, P.; Schuurman, E. J.; Bleeker-Wagemakers, E. M.; Apkarian, P.; van Ommen, G. J.

1993-01-01

Although physical and genetic mapping studies assigned the X-linked ocular albinism gene to Xp22.3, the exact gene order in this region is still unclear. We present additional genetic mapping data concerning X-linked ocular albinism that suggests the consensus order Xpter-STS-DXS237-KAL-(OA1,

Linkage and candidate gene analysis of X-linked familial exudative vitreoretinopathy.

Science.gov (United States)

Shastry, B S; Hejtmancik, J F; Plager, D A; Hartzer, M K; Trese, M T

1995-05-20

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder characterized by avascularity of the peripheral retina, retinal exudates, tractional detachment, and retinal folds. The disorder is most commonly transmitted as an autosomal dominant trait, but X-linked transmission also occurs. To initiate the process of identifying the gene responsible for the X-linked disorder, linkage analysis has been performed with three previously unreported three- or four-generation families. Two-point analysis showed linkage to MAOA (Zmax = 2.1, theta max = 0) and DXS228 (Zmax = 0.5, theta max = 0.11), and this was further confirmed by multipoint analysis with these same markers (Zmax = 2.81 at MAOA), which both lie near the gene causing Norrie disease. Molecular genetic analysis further reveals a missense mutation (R121W) in the third exon of the Norrie's disease gene that perfectly cosegregates with the disease through three generations in one family. This mutation was not detected in the unaffected family members and six normal unrelated controls, suggesting that it is likely to be the pathogenic mutation. Additionally, a polymorphic missense mutation (H127R) was detected in a severely affected patient.

Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility.

Science.gov (United States)

Lu, Xuemei; Shapiro, Joshua A; Ting, Chau-Ti; Li, Yan; Li, Chunyan; Xu, Jin; Huang, Huanwei; Cheng, Ya-Jen; Greenberg, Anthony J; Li, Shou-Hsien; Wu, Mao-Lien; Shen, Yang; Wu, Chung-I

2010-08-01

Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible.

X-linked acrogigantism syndrome: clinical profile and therapeutic responses.

Science.gov (United States)

Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H; Bours, Vincent; Liu, Pengfei; W de Herder, Wouter; Pellegata, Natalia; Lupski, James R; Daly, Adrian F; Stratakis, Constantine A

2015-06-01

X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. © 2015 Society for Endocrinology.

[DIAGNOSTIC VARIATIONS OF X-LINKED MUSCULAR DYSTROPHY WITH CONTRACTURES].

Science.gov (United States)

Kvirkvelia, N; Shakarishvili, R; Gugutsidze, D; Khizanishvili, N

2015-01-01

Case report with review describes X-linked muscular dystrophy with contractures in 28 years old man and his cousin. The disease revealed itself in an early stage (age 5-10), the process was progressing with apparent tendons retraction and contraction, limited movement in the areas of the neck and back of spine, atrophy of shoulder and pelvic yard and back muscles. Intellect was intact. Cardyomyopathy was exhibited. CK was normal. EMG showed classic myopathic features. Muscle biopsy showed different caliber groups of muscle fibers, growth of endo-perimesial connective tissue. Clinical manifestations together with electrophysiological and histological data suggest consistency with Rotthauwe-Mortier-Bayer X-linked muscular dystrophy.

Parametrization of Combined Quantum Mechanical and Molecular Mechanical Methods: Bond-Tuned Link Atoms

Directory of Open Access Journals (Sweden)

Xin-Ping Wu

2018-05-01

Full Text Available Combined quantum mechanical and molecular mechanical (QM/MM methods are the most powerful available methods for high-level treatments of subsystems of very large systems. The treatment of the QM−MM boundary strongly affects the accuracy of QM/MM calculations. For QM/MM calculations having covalent bonds cut by the QM−MM boundary, it has been proposed previously to use a scheme with system-specific tuned fluorine link atoms. Here, we propose a broadly parametrized scheme where the parameters of the tuned F link atoms depend only on the type of bond being cut. In the proposed new scheme, the F link atom is tuned for systems with a certain type of cut bond at the QM−MM boundary instead of for a specific target system, and the resulting link atoms are call bond-tuned link atoms. In principle, the bond-tuned link atoms can be as convenient as the popular H link atoms, and they are especially well adapted for high-throughput and accurate QM/MM calculations. Here, we present the parameters for several kinds of cut bonds along with a set of validation calculations that confirm that the proposed bond-tuned link-atom scheme can be as accurate as the system-specific tuned F link-atom scheme.

Parametrization of Combined Quantum Mechanical and Molecular Mechanical Methods: Bond-Tuned Link Atoms.

Science.gov (United States)

Wu, Xin-Ping; Gagliardi, Laura; Truhlar, Donald G

2018-05-30

Combined quantum mechanical and molecular mechanical (QM/MM) methods are the most powerful available methods for high-level treatments of subsystems of very large systems. The treatment of the QM-MM boundary strongly affects the accuracy of QM/MM calculations. For QM/MM calculations having covalent bonds cut by the QM-MM boundary, it has been proposed previously to use a scheme with system-specific tuned fluorine link atoms. Here, we propose a broadly parametrized scheme where the parameters of the tuned F link atoms depend only on the type of bond being cut. In the proposed new scheme, the F link atom is tuned for systems with a certain type of cut bond at the QM-MM boundary instead of for a specific target system, and the resulting link atoms are call bond-tuned link atoms. In principle, the bond-tuned link atoms can be as convenient as the popular H link atoms, and they are especially well adapted for high-throughput and accurate QM/MM calculations. Here, we present the parameters for several kinds of cut bonds along with a set of validation calculations that confirm that the proposed bond-tuned link-atom scheme can be as accurate as the system-specific tuned F link-atom scheme.

The management of cornea blindness from severe corneal scarring, with the Athens Protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking

Directory of Open Access Journals (Sweden)

Kanellopoulos AJ

2012-02-01

Full Text Available Anastasios John KanellopoulosLaservision.gr Institute, Athens, Greece; Manhattan Eye, Ear and Throat Hospital, New York, NY, USA; New York University Medical School, New York, NY, USAPurpose: To evaluate the safety and efficacy of combined transepithelial topography-guided photorefractive keratectomy (PRK therapeutic remodeling, combined with same-day, collagen cross-linking (CXL. This protocol was used for the management of cornea blindness due to severe corneal scarring.Methods: A 57-year-old man had severe corneal blindness in both eyes. Both corneas had significant central scars attributed to a firework explosion 45 years ago, when the patient was 12 years old. Corrected distance visual acuity (CDVA was 20/100 both eyes (OU with refraction: +4.00, –4.50 at 135° in the right eye and +3.50, –1.00 at 55° in the left. Respective keratometries were: 42.3, 60.4 at 17° and 35.8, 39.1 at 151.3°. Cornea transplantation was the recommendation by multiple cornea specialists as the treatment of choice. We decided prior to considering a transplant to employ the Athens Protocol (combined topography-guided partial PRK and CXL in the right eye in February 2010 and in the left eye in September 2010. The treatment plan for both eyes was designed on the topography-guided wavelight excimer laser platform.Results: Fifteen months after the right eye treatment, the right cornea had improved translucency and was topographically stable with uncorrected distance visual acuity (UDVA 20/50 and CDVA 20/40 with refraction +0.50, –2.00 at 5°. We noted a similar outcome after similar treatment applied in the left eye with UDVA 20/50 and CDVA 20/40 with –0.50, –2.00 at 170° at the 8-month follow-up.Conclusion: In this case, the introduction of successful management of severe cornea abnormalities and scarring with the Athens Protocol may provide an effective alternative to other existing surgical or medical options.Keywords: Athens Protocol, collagen cross-linking

X-linked NDUFA1 gene mutations associated with mitochondrial encephalomyopathy.

NARCIS (Netherlands)

Fernandez-Moreira, D.; Ugalde, C.; Smeets, R.; Rodenburg, R.J.T.; Lopez-Laso, E.; Ruiz-Falco, M.L.; Briones, P.; Martin, M.A.; Smeitink, J.A.M.; Arenas, J.

2007-01-01

OBJECTIVE: Mitochondrial complex I deficiency is the commonest diagnosed respiratory chain defect, being genetically heterogeneous. The male preponderance of previous patient cohorts suggested an X-linked underlying genetic defect. We investigated mutations in the X-chromosomal complex I structural

X-linked gene expression and X-chromosome inactivation: marsupials, mouse, and man compared.

Science.gov (United States)

VandeBerg, J L; Robinson, E S; Samollow, P B; Johnston, P G

1987-01-01

The existence of paternal X inactivation in Australian and American marsupial species suggests that this feature of X-chromosome dosage compensation is not a recent adaptation, but probably predates the evolutionary separation of the Australian and American marsupial lineages. Although it is theoretically possible that the marsupial system is one of random X inactivation with p greater than 0.99 and q less than 0.01 and dependent on parental source, no instance of random X inactivation (p = q or p not equal to q) has ever been verified in any tissue or cell type of any marsupial species. Therefore, we conclude that the most fundamental difference in X inactivation of marsupials and eutherians is whether the inactive X is the paternal one or is determined at random (with p = q in most but not all cases). The only other unequivocal difference between eutherians and marsupials is that both X chromosomes are active in mice and human oocytes, but not in kangaroo oocytes. Apparently, the inactive X is reactivated at a later meiotic stage or during early embryogenesis in kangaroos. X-chromosome inactivation takes place early in embryogenesis of eutherians and marsupials. Extraembryonic membranes of mice exhibit paternal X inactivation, whereas those of humans seem to exhibit random X inactivation with p greater than q (i.e., preferential paternal X inactivation). In general, extraembryonic membranes of marsupial exhibit paternal X inactivation, but the Gpd locus is active on both X chromosomes in at least some cells of kangaroo yolk sac. It is difficult to draw any general conclusion because of major differences in embryogeny of mice, humans, and marsupials, and uncertainties in interpreting the data from humans. Other differences between marsupials and eutherians in patterns of X-linked gene expression and X-chromosome inactivation seem to be quantitative rather than qualitative. Partial expression of some genes on the inactive X is characteristic of marsupials, with

Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome: a paradigm of immunodeficiency with autoimmunity

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Federica eBarzaghi

2012-07-01

Full Text Available Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome is a rare monogenic primary immunodeficiency (PID due to mutations of FOXP3, a key transcription factor for naturally occurring (n regulatory T (Treg cells. The dysfunction of Treg cells is the main pathogenic event leading to the multi-organ autoimmunity that characterizes IPEX syndrome, a paradigm of genetically determined PID with autoimmunity. IPEX has a severe early onset and can become rapidly fatal within the first year of life regardless of the type and site of the mutation. The initial presenting symptoms are severe enteritis and/or type 1 diabetes mellitus, alone or in combination with eczema and elevated serum IgE. Other autoimmune symptoms, such as hypothyroidism, cytopenia, hepatitis, nephropathy, arthritis, and alopecia, can develop in patients who survive the initial acute phase.The current therapeutic options for IPEX patients are limited. Supportive and replacement therapies combined with pharmacological immunosuppression are required to control symptoms at onset. However, these procedures can allow only a reduction of the clinical manifestations without a permanent control of the disease. The only known effective cure for IPEX syndrome is haematopoietic stem cell transplantation, but it is always limited by the availability of a suitable donor and the lack of specific guidelines for bone marrow transplant in the context of this disease.This review aims to summarize the clinical histories and genomic mutations of the IPEX patients described in the literature to date. We will focus on the clinical and immunological features that allow differential diagnosis of IPEX syndrome and distinguish it from other PID with autoimmunity. The efficacy of the current therapies will be reviewed, and possible innovative approaches, based on the latest highlights of the pathogenesis to treat this severe primary autoimmune disease of childhood, will be discussed.

Bilateral macular holes in X-linked retinoschisis: Now the spectrum is wider

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Manoj Gautam

2011-01-01

Full Text Available Bilateral occurrence of macular hole in X-linked retinoschisis is an extremely rare event. Spectral domain optical coherence tomography (OCT findings revealed that formation of a macular hole is secondary to the retinoschisis process alone. Bilateral macular holes should be added to the spectrum of X-linked retinoschisis variations and the retinoschisis process alone should be accounted for their formation.

Mechanically Strong, Polymer Cross-linked Aerogels (X-Aerogels)

Science.gov (United States)

Leventis, Nicholas

2006-01-01

-Aerogels have been demonstrated with several polymers such as polyurethanes/polyureas, epoxies and polyolefins, while crosslinking of approximately 35 different oxide aerogels yields a range of dimensionally stable, porous lightweight materials with unique combinations of structural, magnetic and optical properties. The main theme in materials development for space exploration is multifunction. For example, use of one material for thermal insulation/structural component will free weight for useful payload. In that regard, X-aerogels are evaluated at NASA for cryogenic fuel storage tanks and for spacesuits. Along the same lines, major impact fro X-Aerogels is also expected in commercial applications for thermal/acoustic insulation, in catalytic reformers and converters, in filtration membranes and membranes for fuel cells, as platforms for optical, electrical and magnetic sensors, and as lightweight structural component for aircraft and satellites.

X-linked gene transcription patterns in female and male in vivo, in vitro and cloned porcine individual blastocysts.

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Chi-Hun Park

Full Text Available To determine the presence of sexual dimorphic transcription and how in vitro culture environments influence X-linked gene transcription patterns in preimplantation embryos, we analyzed mRNA expression levels in in vivo-derived, in vitro-fertilized (IVF, and cloned porcine blastocysts. Our results clearly show that sex-biased expression occurred between female and male in vivo blastocysts in X-linked genes. The expression levels of XIST, G6PD, HPRT1, PGK1, and BEX1 were significantly higher in female than in male blastocysts, but ZXDA displayed higher levels in male than in female blastocysts. Although we found aberrant expression patterns for several genes in IVF and cloned blastocysts, similar sex-biased expression patterns (on average were observed between the sexes. The transcript levels of BEX1 and XIST were upregulated and PGK1 was downregulated in both IVF and cloned blastocysts compared with in vivo counterparts. Moreover, a remarkable degree of expression heterogeneity was observed among individual cloned embryos (the level of heterogeneity was similar in both sexes but only a small proportion of female IVF embryos exhibited variability, indicating that this phenomenon may be primarily caused by faulty reprogramming by the somatic cell nuclear transfer (SCNT process rather than in vitro conditions. Aberrant expression patterns in cloned embryos of both sexes were not ameliorated by treatment with Scriptaid as a potent HDACi, although the blastocyst rate increased remarkably after this treatment. Taken together, these results indicate that female and male porcine blastocysts produced in vivo and in vitro transcriptional sexual dimorphisms in the selected X-linked genes and compensation of X-linked gene dosage may not occur at the blastocyst stage. Moreover, altered X-linked gene expression frequently occurred in porcine IVF and cloned embryos, indicating that X-linked gene regulation is susceptible to in vitro culture and the SCNT process

Suspected X-linked facial dysmorphia and growth retardation in related Labrador retriever puppies.

Science.gov (United States)

Dierks, C; Hoffmann, H; Heinrich, F; Hellige, M; Hewicker-Trautwein, M; Distl, O

2017-02-01

Seven male Labrador retriever puppies from four different litters were identified with a brachycephalic-like face and skull, associated with low birth weight, severe growth retardation, and reduced abilities to crawl and suckle, which were not compatible with survival. Excessive doming of the cranium, brachygnathia superior and inferior, and an abnormally opened fontanelle were found in all affected puppies by computed tomography and at post-mortem examination. Pedigree analysis supported an X-linked recessive mode of inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preimplantation genetic diagnosis of X-linked diseases examined by indirect linkage analysis.

Science.gov (United States)

Borgulova, I; Putzova, M; Soldatova, I; Krautova, L; Pecnova, L; Mika, J; Kren, R; Potuznikova, P; Stejskal, D

2015-01-01

Many centers of assisted reproduction in the Czech Republic offer preimplantation genetic diagnosis with fluorescent in situ hybridization (FISH) to couples requiring preimplantation genetic diagnosis (PGD) of X-linked diseases. However, this process results in discarding all male embryos and is not able to distinguish a carrier or healthy female embryo in X-linked recessive disorders. The main aim of this study was to summarize a six-year period of PGD of X-linked monogenic diseases using indirect linkage analysis. We wanted to accentuate the advantage indirect analysis of PGD using multiple displacement amplification (MDA) followed by short tandem repeat (STR) analysis. We present forty-six PGD cycles, including pre-case haplotyping (PGH) panel, for fifteen X-linked diseases. Embryo transfer was made thirty-eight times and gravidity was confirmed in thirteen female probands with a success rate of pregnancy calculated at 42 %. PGD procedure using MDA amplification followed by STR analysis provides help in identifying genetic defects within embryos prior to implantation. The reliability of the method was also supported by high pregnancy rate compared to other publications, which commonly achieved a 30-35 % success rate (Tab. 2, Fig. 1, Ref. 33).

X-linked hydrocephalus : A novel missense mutation in the L1CAM gene

NARCIS (Netherlands)

Sztriha, L; Vos, YJ; Verlind, E; Johansen, J; Berg, B

2002-01-01

X-linked hydrocephalus is associated with mutations in the L1 neuronal cell adhesion molecule gene. L1 protein plays a key role in neurite outgrowth, axonal guidance, and pathfinding during the development of the nervous system. A male is described with X-linked hydrocephalus who had multiple small

Newborn Screening for Severe Combined Immunodeficiency in Israel

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Erez Rechavi

2017-06-01

Full Text Available Newborn screening (NBS programs for severe combined immunodeficiency (SCID, the most severe type of primary immunodeficiency, are being implemented in more and more countries with every passing year. Since October 2015, SCID screening via T cell receptor excision circle (TREC quantification in dried blood spots (DBS has been part of the Israeli NBS program. As an NBS program in its infancy, SCID screening is still evolving, making gathering input from the various programs crucial for compiling an ideal screening algorithm. The relatively high rate of consanguineous marriages in Israel, especially among non-Jews, correlates with an increased incidence of SCID. The Israeli algorithm uses a commercial kit and consists of a two-Guthrie card confirmation system prior to referral to a national immunology center. Preliminary data from the first year and a half of SCID screening in Israel has identified a surprisingly high prevalence of DNA cross-link repair protein 1c (DCLRE1C; ARTEMIS mutations as the cause of SCID in Israel. The clinically unbiased nature of SCID screening helps unearth mild/leaky SCID phenotypes, resulting in a better understanding of true SCID prevalence and etiology.

Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia.

Science.gov (United States)

Kasper, Burkhard S; Kurzbuch, Katrin; Chang, Bernard S; Pauli, Elisabeth; Hamer, Hajo M; Winkler, Jürgen; Hehr, Ute

2013-06-01

Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X-linked dominant inherited, caused by mutations in the Filamin A gene (FLNA) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA-associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X-linked dominant traits like FLNA-associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA-associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X-linked dominant inherited FLNA-associated PNH. Copyright © 2013 Wiley Periodicals, Inc.

Pyoderma gangrenosum-like ulcer in a patient with X-linked agammaglobulinemia: identification of Helicobacter bilis by mass spectrometry analysis.

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Murray, Patrick R; Jain, Ashish; Uzel, Gulbu; Ranken, Raymond; Ivy, Cristina; Blyn, Lawrence B; Ecker, David J; Sampath, Rangarajan; Lee, Chyi-Chia Richard; Turner, Maria L

2010-05-01

Pyoderma gangrenosum-like ulcers and cellulitis of the lower extremities associated with recurrent fevers in patients with X-linked (Bruton) agammaglobulinemia have been reported to be caused by Helicobacter bilis (formerly classified as Flexispira rappini and then Helicobacter strain flexispira taxon 8). Consistent themes in these reports are the difficulty in recovering this organism in blood and wound cultures and in maintaining isolates in vitro. We confirmed the presence of this organism in a patient's culture by using a novel application of gene amplification polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry. An adolescent boy with X-linked agammaglobulinemia presented with indurated plaques and a chronic leg ulcer whose origin was strongly suspected to be an H bilis organism. Histologic analysis demonstrated positive Warthin-Starry staining of curvilinear rods, which grew in culture but failed to grow when subcultured. They could not be identified by conventional techniques. A combination of gene amplification by polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry confirmed the identity of this organism. This novel technology was useful in the identification of a difficult-to-grow Helicobacter organism, the cause of pyoderma gangrenosum-like leg ulcers in patients with X-linked agammaglobulinemia. Correct identification of this organism as the cause of pyoderma gangrenosum-like ulcers in patients with X-linked agammaglobulinemia is of great importance for the early initiation of appropriate and curative antibiotic therapy.

Two Cases of Severe Combined Immunodeficiency Caused By Adenosine Deaminase Deficiency

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Turkan Patiroglu

2014-08-01

Full Text Available Severe Combined Immune Deficiency (SCID is a primary immune deficiency disorder manifested with severe infections upon first months of life, which is characterized by diverse genetic defects in T and B lymphocyte functions and occasionally in NK cells. ADA deficiency is a form of SCID progressing with severe lymphopenia and immune deficiency caused by toxic metabolites of ADA. Bone marrow transplantation (BMT is the only curative treatment although prophylactic anti-microbial therapy, intravenous immunoglobulin (IVIG and enzyme replacement can achieve transient improvements. Early diagnosis before development of severe infections and organ injury and referral to pediatric immunology clinics will make considerable contributions to prognosis. Here, we presented 2 cousins with SCID who had positive family history with deceased sibling; presented with tanning at skin, severe neonatal infections and Q246X (c736C>T non-sense mutation in exon 8 in ADA gene  in order to emphasize this rare mutation and pediatric emergencies associated with this disorder.

X-ray-mediated cross linking of protein and DNA

International Nuclear Information System (INIS)

Minsky, B.D.; Braun, A.

1977-01-01

Using a simple filter assay for the binding of BSA or lysozyme to DNA, two mechanisms of x-ray-mediated cross linking are shown to occur. One, a fast reaction, appears to involve a radical intermediate, is inhibited by high pH and salt, and seems to be enhanced by deoxygenation. The second mechanism, a slow time-dependent component, differs from the fast reaction in its stimulation by histidine, its inhibition by catalase, and the lack of an oxygen effect. Separate irradiation of DNA or water does not lead to cross linking. However, separate irradiation of protein leads to cross linking which proceeds with slow-component kinetics

Dynamic Copy Number Evolution of X- and Y-Linked Ampliconic Genes in Human Populations

DEFF Research Database (Denmark)

Lucotte, Elise A; Skov, Laurits; Jensen, Jacob Malte

2018-01-01

we explore the evolution of human X- and Y-linked ampliconic genes by investigating copy number variation (CNV) and coding variation between populations using the Simons Genome Diversity Project. We develop a method to assess CNVs using the read-depth on modified X and Y chromosome targets containing...... related Y haplogroups, that diversified less than 50,000 years ago. Moreover, X and Y-linked ampliconic genes seem to have a faster amplification dynamic than autosomal multicopy genes. Looking at expression data from another study, we also find that XY-linked ampliconic genes with extensive copy number...

The management of cornea blindness from severe corneal scarring, with the Athens Protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking).

Science.gov (United States)

Kanellopoulos, Anastasios John

2012-01-01

To evaluate the safety and efficacy of combined transepithelial topography-guided photorefractive keratectomy (PRK) therapeutic remodeling, combined with same-day, collagen cross-linking (CXL). This protocol was used for the management of cornea blindness due to severe corneal scarring. A 57-year-old man had severe corneal blindness in both eyes. Both corneas had significant central scars attributed to a firework explosion 45 years ago, when the patient was 12 years old. Corrected distance visual acuity (CDVA) was 20/100 both eyes (OU) with refraction: +4.00, -4.50 at 135° in the right eye and +3.50, -1.00 at 55° in the left. Respective keratometries were: 42.3, 60.4 at 17° and 35.8, 39.1 at 151.3°. Cornea transplantation was the recommendation by multiple cornea specialists as the treatment of choice. We decided prior to considering a transplant to employ the Athens Protocol (combined topography-guided partial PRK and CXL) in the right eye in February 2010 and in the left eye in September 2010. The treatment plan for both eyes was designed on the topography-guided wavelight excimer laser platform. Fifteen months after the right eye treatment, the right cornea had improved translucency and was topographically stable with uncorrected distance visual acuity (UDVA) 20/50 and CDVA 20/40 with refraction +0.50, -2.00 at 5°. We noted a similar outcome after similar treatment applied in the left eye with UDVA 20/50 and CDVA 20/40 with -0.50, -2.00 at 170° at the 8-month follow-up. In this case, the introduction of successful management of severe cornea abnormalities and scarring with the Athens Protocol may provide an effective alternative to other existing surgical or medical options.

X-linked creatine transporter deficiency: clinical aspects and pathophysiology

NARCIS (Netherlands)

van de Kamp, J.M.; Mancini, G.M.; Salomons, G.S.

2014-01-01

Creatine transporter deficiency was discovered in 2001 as an X-linked cause of intellectual disability characterized by cerebral creatine deficiency. This review describes the current knowledge regarding creatine metabolism, the creatine transporter and the clinical aspects of creatine transporter

Genetics Home Reference: X-linked congenital stationary night blindness

Science.gov (United States)

... collapse boxes. Description X-linked congenital stationary night blindness is a disorder of the retina , which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing ...

Algorithm of dynamic stabilization system for a car 4x4 with a link rear axle

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M. M. Jileikin

2014-01-01

Full Text Available The slow development of active safety systems of the automobile all-wheel drive vehicles is the cause of lack of researches in the field of power distribution under the specific conditions of movement. The purpose of work is to develop methods to control a curvilinear motion of 4x4 cars with a link to the rear axle that provides the increase in directional and trajectory stability of the car. The paper analyses the known methods to increase wheeled vehicles movement stability. It also offers a method for power flow redistribution in the transmission of the car 4x4 with a link to the rear axle, providing the increase in directional and trajectory stability of the car.To study the performance and effectiveness of the proposed method a mathematical model of the moving car 4x4 with a link to the rear axle is developed. Simulation methods allowed us to establish the following:1. for car 4x4 with redistribution of torque between the driving axles in the range of 100:0 - 50:50 and with redistribution of torque between the wheels of the rear axle in the range of 0:100 the most effective are the stabilization algorithms used in combination “Lowing power consumption of the engine +Creation of stabilizing the moment due to the redistribution of torque on different wheels", providing the increase in directional and trajectory stability by 12...93%;2. for car 4x4 with redistribution of torque between the driving axles in the range 100:0 - 0:100 and with redistribution of torque between the wheels of the rear axle in the range of 0:100 the best option is a combination of algorithms "Lowing power consumption of the engine + Creation of stabilizing moment due to redistribution of torques on different wheels", providing the increase in directional and trajectory stability by 27...93%.A comparative analysis of algorithms efficiency of dynamic stabilization system operation for two-axle wheeled vehicles depending on the torque redistribution between the driving

High-resolution mapping of the x-linked hypohidrotic ectodermal dysplasia (EDA) locus

Energy Technology Data Exchange (ETDEWEB)

Zonana, J.; Jones, M.; Litt, M.; Kramer, P.; Browne, D.; Becker, H.W. (Oregon Health Sciences Univ., Portland, OR (United States)); Brockdorff, N.; Rastan, S. (Medical Council Clinical Research Centre, Harrow (United Kingdom)); Davies, K.P.; Clarke, A. (Univ. of Wales College of Medicine, Cardiff (United Kingdom)) (and others)

1992-11-01

The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. The authors have extended previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analysis gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci could be inferred from a human-rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosites of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that consegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXSA732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively. 36 refs., 1 fig., 5 tabs.

X-linked Hyper IgM Syndrome Presenting as Pulmonary Alveolar Proteinosis.

Science.gov (United States)

Gallagher, Joel; Adams, Juan; Hintermeyer, Mary; Torgerson, Troy R; Lopez-Guisa, Jesus; Ochs, Hans D; Szabo, Sara; Salib, Mina; Verbsky, James; Routes, John

2016-08-01

X-linked hyper IgM syndrome (XHIGM) is a combined immunodeficiency caused by mutations in the CD40 ligand (CD40L) gene that typically results in decreased or absent CD40L expression on activated T cells, leading to defective class switching and somatic hypermutation. We describe an infant who presented with respiratory failure due to pulmonary alveolar proteinosis (PAP) with a novel damaging missense mutation in the CD40L gene. Whole exome sequencing (WES) was used to identify a mutation in the CD40L gene. CD40L expression and function were determined by flow cytometry. A 5-month-old previously-healthy male presented with respiratory failure and diffuse pulmonary ground glass opacities on CT scan of the chest. Laboratory evaluation revealed an undetectable IgG, normal IgA, and elevated IgM. A bronchoalveolar lavage demonstrated pulmonary alveolar proteinosis. WES demonstrated a c.608G > C mutation in the CD40L gene resulting in p.R203T. Flow cytometry demonstrated normal CD40L expression on activated T cells but absent binding of CD40-Ig to CD40L on activated patient T cells. The clinical manifestations of XHIGM in our patient had several unique features, including the presentation with PAP, normal serum IgA, and expression of non-functional CD40L on activated T cells. To our knowledge, this is the first published case of PAP in a patient with XHIGM.

Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

Science.gov (United States)

... Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia Printable PDF Open All Close ... boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

Apparent X-linked primary ciliary dyskinesia associated with retinitis pigmentosa and a hearing loss.

Science.gov (United States)

Krawczyński, Maciej R; Dmeńska, Hanna; Witt, Michał

2004-01-01

Three brothers, one 10-year-old and a pair of 14-year-old dizygotic twins--expressed the classical, early-onset retinitis pigmentosa (RP) with typical ophthalmoscopic findings, night blindness, visual field constricted to 10 degrees and flat ERG response. All three brothers were also diagnosed with primary ciliary dyskinesia (PCD) and had recurrent respiratory infections, chronic sinusitis and bronchiectasis. In all of them, resection of the middle lobe of the right lung was performed. A similar clinical picture of coexisting RP and PCD was noted in the brother of the probands' mother. All probands displayed situs solitus. Consistent with the X-linked mode of RP inheritance, there were also three obligatory female carriers of the disorder in this family: the mother of the affected boys, her mother and a daughter of her brother. In all of them, retinitis pigmentosa "sine pigmento" was found with milder but clinically significant symptoms (mild night blindness, visual field constricted to 30 degrees, and scotopic and photopic ERG responses reduced to 30-60%). No extraocular symptoms were detected in any of the heterozygous female carriers. This family presents an example of two rare phenomena: X-linked dominant retinitis pigmentosa (with milder expression in females) and a rare combination of RP with recurrent respiratory infections due to PCD.

Genetic localization and phenotypic expression of X-linked cataract (Xcat) in Mus musculus.

Science.gov (United States)

Favor, J; Pretsch, W

1990-01-01

Linkage data relative to the markers tabby and glucose-6-phosphate dehydrogenase are presented to locate X-linked cataract (Xcat) in the distal portion of the mouse X-chromosome between jimpy and hypophosphatemia. The human X-linked cataract-dental syndrome, Nance-Horan Syndrome, also maps closely to human hypophosphatemia and would suggest homology between mouse Xcat and human Nance-Horan Syndrome genes. In hemizygous males and homozygous females penetrance is complete with only slight variation in the degree of expression. Phenotypic expression in Xcat heterozygous females ranges from totally clear to totally opaque lenses. The phenotypic expression between the two lenses of a heterozygous individual could also vary between totally clear and totally opaque lenses. However, a correlation in the degree of expression between the eyes of an individual was observed. A variegated pattern of lens opacity was evident in female heterozygotes. Based on these observations, the site of gene action for the Xcat locus is suggested to be endogenous to the lens cells and the precursor cell population of the lens is concluded to be small. The identification of an X-linked cataract locus is an important contribution to the estimate of the number of mutable loci resulting in cataract, an estimate required so that dominant cataract mutagenesis results may be expressed on a per locus basis. The Xcat mutation may be a useful marker for a distal region of the mouse X-chromosome which is relatively sparsely marked and the X-linked cataract mutation may be employed in gene expression and lens development studies.

Lentiviral hematopoietic cell gene therapy for X-linked adrenoleukodystrophy.

Science.gov (United States)

Cartier, Nathalie; Hacein-Bey-Abina, Salima; Bartholomae, Cynthia C; Bougnères, Pierre; Schmidt, Manfred; Kalle, Christof Von; Fischer, Alain; Cavazzana-Calvo, Marina; Aubourg, Patrick

2012-01-01

X-linked adrenoleukodystrophy (X-ALD) is a severe genetic demyelinating disease caused by a deficiency in ALD protein, an adenosine triphosphate-binding cassette transporter encoded by the ABCD1 gene. When performed at an early stage of the disease, allogeneic hematopoietic stem cell transplantation (HCT) can arrest the progression of cerebral demyelinating lesions. To overcome the limitations of allogeneic HCT, hematopoietic stem cell (HSC) gene therapy strategy aiming to perform autologous transplantation of lentivirally corrected cells was developed. We demonstrated the preclinical feasibility of HSC gene therapy for ALD based on the correction of CD34+ cells from X-ALD patients using an HIV1-derived lentiviral vector. These results prompted us to initiate an HSC gene therapy trial in two X-ALD patients who had developed progressive cerebral demyelination, were candidates for allogeneic HCT, but had no HLA-matched donors or cord blood. Autologous CD34+ cells were purified from the peripheral blood after G-CSF stimulation, genetically corrected ex vivo with a lentiviral vector encoding wild-type ABCD1 cDNA, and then reinfused into the patients after they had received full myeloablative conditioning. Over 3 years of follow-up, the hematopoiesis remained polyclonal in the two patients treated with 7-14% of granulocytes, monocytes, and T and B lymphocytes expressing the lentivirally encoded ALD protein. There was no evidence of clonal dominance or skewing based on the retrieval of lentiviral insertion repertoire in different hematopoietic lineages by deep sequencing. Cerebral demyelination was arrested 14 and 16months, respectively, in the two treated patients, without further progression up to the last follow-up, a clinical outcome that is comparable to that observed after allogeneic HCT. Longer follow-up of these two treated patients and HSC gene therapy performed in additional ALD patients are however needed to evaluate the safety and efficacy of lentiviral HSC

Determination of electronic and atomic properties of surface, bulk and buried interfaces: Simultaneous combination of hard X-ray photoelectron spectroscopy and X-ray diffraction

Energy Technology Data Exchange (ETDEWEB)

Rubio-Zuazo, J., E-mail: rubio@esrf.fr [SpLine, Spanish CRG BM25 Beamline at the ESRF, ESRF, B.P. 220, F-38043 Grenoble (France); Instituto de Ciencia de Materiales de Madrid, ICMM, CSIC, Cantoblanco, E-28049 Madrid (Spain); Castro, G.R. [SpLine, Spanish CRG BM25 Beamline at the ESRF, ESRF, B.P. 220, F-38043 Grenoble (France); Instituto de Ciencia de Materiales de Madrid, ICMM, CSIC, Cantoblanco, E-28049 Madrid (Spain)

2013-10-15

Highlights: •We have developed a novel and exceptional tool for non-destructive characterization of bulk and buried interfaces that combine XRD and HAXPES. •We studied the correlation between the atomic, electronic and transport properties of oxygen deficient manganite thin films. •The diffraction data showed a cooperative tilt of the MnO{sub 6} block along the out-of-plane direction. •We shown the absence of the conventional basal plane rotation for the oxygen deficient samples. -- Abstract: Hard X-ray photoelectron spectroscopy (HAXPES) is a powerful novel emerging technique for bulk compositional, chemical and electronic properties determination in a non-destructive way. It benefits from the exceptionally large escape depth of high kinetic energy photoelectrons enabling the study of bulk and buried interfaces up to several tens of nanometres depth. Its advantage over conventional XPS is based on the long mean free path of high kinetic energetic photoelectrons. Using the advantage of tuneable X-ray radiation provided by synchrotron sources the photoelectron kinetic energy, i.e. the information depth can be changed and consequently electronic and compositional depth profiles can be obtained. The combination of HAXPES with an atomic structure sensitive technique, as X-ray diffraction, opens a new research field with great potential for many systems in which their electronic properties are intimately linked to their crystallographic structure. At SpLine, the Spanish CRG Beamline at the European Synchrotron Radiation Facility (ESRF) we have developed a novel and exceptional set-up that combine grazing incidence X-ray diffraction (GIXRD) and HAXPES. Both techniques can be operated simultaneously on the same sample and using the same excitation source. The set-up includes a heavy 2S+3D diffractometer and UHV chamber equipped with an electrostatic analyzer. The UHV chamber has also MBE evaporation sources, an ion gun, a LEED optic, a sample heating and cooling

An X-linked homologue of the autosomal inprinted gene ZNF127 escapes X inactivation

Energy Technology Data Exchange (ETDEWEB)

Longstreet, M.; Nicholls, R.D.; Willard, H.F. [Case Western Reserve Univ., Cleveland, OH (United States)] [and others

1994-09-01

The ZNF127 gene has been shown to be subject to parental imprinting in both humans and the mouse and maps to within the Prader-Willi/Angelman Syndrome critical region on chromosome 15. We have cloned two X-linked related loci, one of which, ZNFXp is a transcribed gene while the other, ZNFXq, is an untranscribed pseudogene. ZNFXp is 83.6% identical to ZNFXq and 65.4% identical to ZNF127 over 1.4 kb of open reading frame they share in common, Like ZNF127, the predicted protein sequence of ZNFXp contains a C{sub 3}HC{sub 4} zinc finger domain and C{sub 3}H zinc finger-like motifs. Whereas ZNF127 has three C{sub 3}H motifs, ZNFXp has four. A strong CpG island is located within 1 kb 5{prime} of the predicted amino terminus of ZNFXp. Expression of ZNFXp has been detected from mouse/human somatic cell hybrids containing either an active (n=2) or an inactive (n=4) chromosome, and thus escapes X inactivation. Probes made from the 3{prime} UTR of ZNFXp detect a number of related loci in both human and murine DNA, none of which is the ZNF127 locus on chromosome 15. None of the detectable murine bands shows dosage differences between males and females as would be expected for X-linked loci. This raises the possibility that ZNFXp inserted into the human X chromosome after its divergence from a common ancestor with the murine X. We have mapped ZNFXp to Xp11.4 by Southern blotting and PCR of hybrid DNAs and by fluorescence in situ hybridization (FISH). ZNFXq maps within the X Inactivation Center (XIC) region on Xq13.2, approximately 300 kb distal to the XIST gene. We find it intriguing, and perhaps significant, that two members of this gene family are subject to epigenetic regulation -- one autosomal imprinting, and the other escape from X inactivation. These results could imply an evolutionary and mechanistic relationship between these two processes.

Identifying structural variants using linked-read sequencing data.

Science.gov (United States)

Elyanow, Rebecca; Wu, Hsin-Ta; Raphael, Benjamin J

2017-11-03

Structural variation, including large deletions, duplications, inversions, translocations, and other rearrangements, is common in human and cancer genomes. A number of methods have been developed to identify structural variants from Illumina short-read sequencing data. However, reliable identification of structural variants remains challenging because many variants have breakpoints in repetitive regions of the genome and thus are difficult to identify with short reads. The recently developed linked-read sequencing technology from 10X Genomics combines a novel barcoding strategy with Illumina sequencing. This technology labels all reads that originate from a small number (~5-10) DNA molecules ~50Kbp in length with the same molecular barcode. These barcoded reads contain long-range sequence information that is advantageous for identification of structural variants. We present Novel Adjacency Identification with Barcoded Reads (NAIBR), an algorithm to identify structural variants in linked-read sequencing data. NAIBR predicts novel adjacencies in a individual genome resulting from structural variants using a probabilistic model that combines multiple signals in barcoded reads. We show that NAIBR outperforms several existing methods for structural variant identification - including two recent methods that also analyze linked-reads - on simulated sequencing data and 10X whole-genome sequencing data from the NA12878 human genome and the HCC1954 breast cancer cell line. Several of the novel somatic structural variants identified in HCC1954 overlap known cancer genes. Software is available at compbio.cs.brown.edu/software. braphael@princeton.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Cochlear implantation in X-linked deafness - How to manage the surgical challenges.

Science.gov (United States)

Saeed, Haroon; Powell, Harry R F; Saeed, Shakeel R

2016-07-01

In children with X-linked deafness, cochlear malformations challenge the implant surgeon to avoid electrode insertion into the internal auditory meatus and prevent a continuous cerebrospinal fluid (CSF) leak. We describe our experience of cochlear implantation (CI) in two children with profound hearing loss secondary to X-linked deafness, highlighting safer operative techniques to avoid potential complications. Descriptive cases of two children with X-linked deafness (patient 1 and patient 2) undergoing CI. Peri-operative imaging and work-up to surgery are discussed. Specific operative considerations, post-operative complications and subsequent audiological performance are highlighted. In each case, intra-operative fluoroscopic imaging ensured intra-cochlear insertion of electrodes. Expected CSF gusher was seen in each case which was initially controlled by packing around the cochleostomy and array with temporalis muscle and fascia. Patient 1 developed post-operative meningitis secondary to continuous CSF leak. We avoided further significant CSF leak by planning staged procedures for patient 2, with obliteration of the middle ear cleft and external ear canal (EAC) at the time of implantation. In both patients, bilateral implantation successfully provided hearing thresholds of less than 35 dB in both ears at routine follow up. When planning for CI in children with radiological features of X-linked deafness, intra-operative imaging should be utilized to ensure correct electrode positioning. Traditional methods of stopping a CSF gusher may not suffice. We therefore encourage additional surgical obliteration of the middle ear space and EAC to avoid persistent CSF leak and its associated complications.

Diagnosis of X-Linked Hypohidrotic Ectodermal Dysplasia by Meibography and Infrared Thermography of the Eye.

Science.gov (United States)

Kaercher, Thomas; Dietz, Jasna; Jacobi, Christina; Berz, Reinhold; Schneider, Holm

2015-09-01

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical characteristics include meibomian gland disorder and the resulting hyperevaporative dry eye. In this study, we evaluated meibography and ocular infrared thermography as novel methods to diagnose XLHED. Eight infants, 12 boys and 14 male adults with XLHED and 12 healthy control subjects were subjected to a panel of tests including the ocular surface disease index (OSDI), meibography and infrared thermography, non-invasive measurement of tear film break-up time (NIBUT) and osmolarity, Schirmer's test, lissamine green staining and fluorescein staining. Sensitivity and specificity were determined for single tests and selected test combinations. Meibography had 100% sensitivity and specificity for identifying XLHED. Infrared thermography, a completely non-invasive procedure, revealed a typical pattern for male subjects with XLHED. It was, however, less sensitive (86% for adults and 67% for children) than meibography or a combination of established routine tests. In adults, OSDI and NIBUT were the best single routine tests (sensitivity of 86% and 71%, respectively), whereas increased tear osmolarity appeared as a rather unspecific ophthalmic symptom. In children, NIBUT was the most convincing routine test (sensitivity of 91%). Meibography is the most reliable ophthalmic examination to establish a clinical diagnosis in individuals with suspected hypohidrotic ectodermal dysplasia, even before genetic test results are available. Tear film tests and ocular surface staining are less sensitive in children, but very helpful for estimating the severity of ocular surface disease in individuals with known XLHED.

Combined exposure of ELF magnetic fields and X-rays increased mutant yields compared with X-rays alone in pTN89 plasmids

International Nuclear Information System (INIS)

Koyama, Shin; Nakahara, Takehisa; Sakurai, Tomonori; Komatsubara, Yoshiki; Miyakoshi, Junji; Isozumi, Yasuhito

2005-01-01

We have examined mutations in the supF gene carried by pTN89 plasmids in Escherichia coli (E. coli) to examine the effects of extremely low frequency magnetic fields (ELFMFs) and/or X-rays to the plasmids. The plasmids were subjected to sham exposure or exposed to an ELFMF (5 mT), with or without X-ray irradiation (10 Gy). For the combined treatments, exposure to the ELFMF was immediately before or after X-ray irradiation. The mutant fractions were 0.94 x 10 -5 for X-rays alone, 1.58 x 10 -5 for an ELFMF followed by X-rays, and 3.64 x 10 -5 for X-rays followed by an ELFMF. Increased mutant fraction was not detected following exposure to a magnetic field alone, or after sham exposure. The mutant fraction for X-rays followed by an ELFMF was significantly higher than those of other treatments. Sequence analysis of the supF mutant plasmids revealed that base substitutions were dominant on exposure to X-rays alone and X-rays plus an ELFMF. Several types of deletions were detected in only the combined treatments, but not with X-rays alone. We could not find any mutant colonies in sham irradiated and an ELFMF alone treatment, but exposure to ELFMFs immediately before or after X-ray irradiation may enhance the mutations. Our results indicate that an ELFMF increases mutation and alters the spectrum of mutations. (author)

Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

Directory of Open Access Journals (Sweden)

Claudia A Montiel-Equihua

2009-12-01

Full Text Available Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID and especially adenosine deaminase (ADA-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID.Keywords: adenosine deaminase, severe combined immunodeficiency, gene therapy, hematopoietic stem cell, retrovirus, clinical trial

CAPILLARY NETWORK ALTERATIONS IN X-LINKED RETINOSCHISIS IMAGED ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Science.gov (United States)

Romano, Francesco; Arrigo, Alessandro; Chʼng, Soon Wai; Battaglia Parodi, Maurizio; Manitto, Maria Pia; Martina, Elisabetta; Bandello, Francesco; Stanga, Paulo E

2018-06-05

To assess foveal and parafoveal vasculature at the superficial capillary plexus, deep capillary plexus, and choriocapillaris of patients with X-linked retinoschisis by means of optical coherence tomography angiography. Six patients with X-linked retinoschisis (12 eyes) and seven healthy controls (14 eyes) were recruited and underwent complete ophthalmologic examination, including best-corrected visual acuity, dilated fundoscopy, and 3 × 3-mm optical coherence tomography angiography macular scans (DRI OCT Triton; Topcon Corp). After segmentation and quality review, optical coherence tomography angiography slabs were imported into ImageJ 1.50 (NIH; Bethesda) and digitally binarized. Quantification of vessel density was performed after foveal avascular zone area measurement and exclusion. Patients were additionally divided into "responders" and "nonresponders" to dorzolamide therapy. Foveal avascular zone area resulted markedly enlarged at the deep capillary plexus (P < 0.001), particularly in nonresponders. Moreover, patients disclosed a significant deep capillary plexus rarefaction, when compared with controls (P: 0.04); however, a subanalysis revealed that this damage was limited to the fovea (P: 0.006). Finally, the enlargement of foveal avascular zone area positively correlated with a decline in best-corrected visual acuity (P: 0.01). Prominent foveal vascular impairment is detectable in the deep capillary plexus of patients with X-linked retinoschisis. Our results correlate with functional outcomes, suggesting a possible vascular role in X-linked retinoschisis clinical manifestations.

Successful treatment with infliximab for inflammatory colitis in a patient with X-linked anhidrotic ectodermal dysplasia with immunodeficiency.

Science.gov (United States)

Mizukami, Tomoyuki; Obara, Megumi; Nishikomori, Ryuta; Kawai, Tomoki; Tahara, Yoshihiro; Sameshima, Naoki; Marutsuka, Kousuke; Nakase, Hiroshi; Kimura, Nobuhiro; Heike, Toshio; Nunoi, Hiroyuki

2012-02-01

X-linked anhidrotic ectodermal dysplasia with immunodeficiency (X-EDA-ID) is caused by hypomorphic mutations in the gene encoding nuclear factor-κB essential modulator protein (NEMO). Patients are susceptibile to diverse pathogens due to insufficient cytokine and frequently show severe chronic colitis. An 11-year-old boy with X-EDA-ID was hospitalized with autoimmune symptoms and severe chronic colitis which had been refractory to immunosuppressive drugs. Since tumor necrosis factor (TNF) α is responsible for the pathogenesis of NEMO colitis according to intestinal NEMO and additional TNFR1 knockout mice studies, and high levels of TNFα-producing mononuclear cells were detected in the patient due to the unexpected gene reversion mosaicism of NEMO, an anti-TNFα monoclonal antibody was administered to ameliorate his abdominal symptoms. Repeated administrations improved his colonoscopic findings as well as his dry skin along with a reduction of TNFα-expressing T cells. These findings suggest TNF blockade therapy is of value for refractory NEMO colitis with gene reversion.

X linked neonatal centronuclear/myotubular myopathy: evidence for linkage to Xq28 DNA marker loci.

OpenAIRE

Thomas, N S; Williams, H; Cole, G; Roberts, K; Clarke, A; Liechti-Gallati, S; Braga, S; Gerber, A; Meier, C; Moser, H

1990-01-01

We have studied the inheritance of several polymorphic Xq27/28 DNA marker loci in two three generation families with the X linked neonatal lethal form of centronuclear/myotubular myopathy (XL MTM). We found complete linkage of XLMTM to all four informative Xq28 markers analysed, with GCP/RCP (Z = 3.876, theta = 0.00), with DXS15 (Z = 3.737, theta = 0.00), with DXS52 (Z = 2.709, theta = 0.00), and with F8C (Z = 1.020, theta = 0.00). In the absence of any observable recombination, we are unable...

Subcortical laminar heterotopia and lissencephaly in two families: a single X linked dominant gene.

Science.gov (United States)

Pinard, J M; Motte, J; Chiron, C; Brian, R; Andermann, E; Dulac, O

1994-01-01

Neuronal migration disorders can now be recognised by MRI. This paper reports two families in which the mothers had subcortical laminar heterotopia and four of their children had either similar heterotopia (two girls) or severe pachygyria or lissencephaly (two boys). Laminar heterotopia was more evident on MRI T2 weighted images. The patients had mild to severe epilepsy and mental retardation depending on the extent of cortical abnormalities. In these families, subcortical laminar heterotopia, pachygyria, and lissencephaly seem to share the same X linked or autosomal dominant gene. No chromosomal abnormalities, especially of chromosome 17, could be identified. For appropriate genetic counselling of the family of a child with lissencephaly or subcortical laminar heterotopia, MRI should be performed in parents or siblings with mental retardation or epilepsy. Images PMID:8057113

A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic diabetes insipidus in two brothers.

Science.gov (United States)

Schernthaner-Reiter, Marie Helene; Adams, David; Trivellin, Giampaolo; Ramnitz, Mary Scott; Raygada, Margarita; Golas, Gretchen; Faucz, Fabio R; Nilsson, Ola; Nella, Aikaterini A; Dileepan, Kavitha; Lodish, Maya; Lee, Paul; Tifft, Cynthia; Markello, Thomas; Gahl, William; Stratakis, Constantine A

2016-05-01

X-linked nephrogenic diabetes insipidus (NDI, OMIM#304800) is caused by mutations in the arginine vasopressin (AVP, OMIM*192340) receptor type 2 (AVPR2, OMIM*300538) gene. A 20-month-old boy and his 8-year-old brother presented with polyuria, polydipsia, and failure to thrive. Both boys demonstrated partial DDAVP (1-desamino-8-D AVP or desmopressin) responses; thus, NDI diagnosis was delayed. While routine sequencing of AVPR2 showed a potential splice site variant, it was not until exome sequencing confirmed the AVPR2 splice site variant and did not reveal any more likely candidates that the patients' diagnosis was made and proper treatment was instituted. Both patients were hemizygous for two AVPR2 variants predicted in silico to affect AVPR2 messenger RNA (mRNA) splicing. A minigene assay revealed that the novel AVPR2 c.276A>G mutation creates a novel splice acceptor site leading to 5' truncation of AVPR2 exon 2 in HEK293 human kidney cells. Both patients have been treated with high-dose DDAVP with a remarkable improvement of their symptoms and accelerated linear growth and weight gain. We present here a unique case of partial X-linked NDI due to an AVPR2 splice site mutation; patients with diabetes insipidus of unknown etiology may harbor splice site mutations that are initially underestimated in their pathogenicity on sequence analysis. • X-linked nephrogenic diabetes insipidus is caused by AVPR2 mutations, and disease severity can vary depending on the functional effect of the mutation. What is New: • We demonstrate here that a splice site mutation in AVPR2 leads to partial X-linked NDI in two brothers. • Treatment with high-dose DDAVP led to improvement of polyuria and polydipsia, weight gain, and growth.

A heterozygous mutation in RPGR associated with X-linked retinitis pigmentosa in a patient with Turner syndrome mosaicism (45,X/46,XX).

Science.gov (United States)

Zhou, Qi; Yao, Fengxia; Wang, Feng; Li, Hui; Chen, Rui; Sui, Ruifang

2018-01-01

Turner syndrome with retinitis pigmentosa (RP) is rare, with only three cases reported based on clinical examination alone. We summarized the 4-year follow-up and molecular findings in a 28-year-old patient with Turner syndrome and the typical features of short stature and neck webbing, who also had X-linked RP. Her main complaints were night blindness and progressive loss of vision since the age of 9 years. Ophthalmologic examination, optical coherent tomographic imaging, and visual electrophysiology tests showed classic manifestations of RP. The karyotype of peripheral blood showed mosaicism (45,X [72%]/46,XX[28%]). A novel heterozygous frameshift mutation (c.2403_2406delAGAG, p.T801fsX812) in the RP GTPase regulator (RPGR) gene was detected using next generation sequencing and validated by Sanger sequencing. We believe that this is the first report of X-linked RP in a patient with Turner syndrome associated with mosaicism, and an RPGR heterozygous mutation. We hypothesize that X-linked RP in this woman is not related to Turner syndrome, but may be a manifestation of the lack of a normal paternal X chromosome with intact but mutated RPGR. © 2017 Wiley Periodicals, Inc.

Learning about Severe Combined Immunodeficiency (SCID)

Science.gov (United States)

... immunodeficiency From The Journal of Allergy and Clinical Immunology Learning About Severe Combined Immunodeficiency (SCID) What is ... immunodeficiency From The Journal of Allergy and Clinical Immunology Get Email Updates Privacy Copyright Contact Accessibility Plug- ...

Delineation of the KIAA2022 mutation phenotype: two patients with X-linked intellectual disability and distinctive features.

Science.gov (United States)

Kuroda, Yukiko; Ohashi, Ikuko; Naruto, Takuya; Ida, Kazumi; Enomoto, Yumi; Saito, Toshiyuki; Nagai, Jun-Ichi; Wada, Takahito; Kurosawa, Kenji

2015-06-01

Next-generation sequencing has enabled the screening for a causative mutation in X-linked intellectual disability (XLID). We identified KIAA2022 mutations in two unrelated male patients by targeted sequencing. We selected 13 Japanese male patients with severe intellectual disability (ID), including four sibling patients and nine sporadic patients. Two of thirteen had a KIAA2022 mutation. Patient 1 was a 3-year-old boy. He had severe ID with autistic behavior and hypotonia. Patient 2 was a 5-year-old boy. He also had severe ID with autistic behavior, hypotonia, central hypothyroidism, and steroid-dependent nephrotic syndrome. Both patients revealed consistent distinctive features, including upswept hair, narrow forehead, downslanting eyebrows, wide palpebral fissures, long nose, hypoplastic alae nasi, open mouth, and large ears. De novo KIAA2022 mutations (p.Q705X in Patient 1, p.R322X in Patient 2) were detected by targeted sequencing and confirmed by Sanger sequencing. KIAA2022 mutations and alterations have been reported in only four families with nonsyndromic ID and epilepsy. KIAA2022 is highly expressed in the fetal and adult brain and plays a crucial role in neuronal development. These additional patients support the evidence that KIAA2022 is a causative gene for XLID. © 2015 Wiley Periodicals, Inc.

X-linked inhibitor of apoptosis regulates T cell effector function

DEFF Research Database (Denmark)

Zehntner, Simone P; Bourbonnière, Lyne; Moore, Craig S

2007-01-01

To understand how the balance between pro- and anti-apoptotic signals influences effector function in the immune system, we studied the X-linked inhibitor of apoptosis (XIAP), an endogenous regulator of cellular apoptosis. Real-time PCR showed increased XIAP expression in blood of mice with exper......To understand how the balance between pro- and anti-apoptotic signals influences effector function in the immune system, we studied the X-linked inhibitor of apoptosis (XIAP), an endogenous regulator of cellular apoptosis. Real-time PCR showed increased XIAP expression in blood of mice...... dramatically reduced within the CNS. Flow cytometry showed an 88-93% reduction in T cells. The proportion of TUNEL(+) apoptotic CD4(+) T cells in the CNS was increased from Neurons...... and oligodendrocytes were not affected; neither did apoptosis increase in liver, where XIAP knockdown also occurred. ASO-XIAP increased susceptibility of T cells to activation-induced apoptosis in vitro. Our results identify XIAP as a critical controller of apoptotic susceptibility of effector T cell function...

A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells

NARCIS (Netherlands)

Kuijpers, Taco W.; van Leeuwen, Ester M. M.; Barendregt, Barbara H.; Klarenbeek, Paul; Aan de Kerk, Daan J.; Baars, Paul A.; Jansen, Machiel H.; de Vries, Niek; van Lier, René A. W.; van der Burg, Mirjam

2013-01-01

Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined

X-Linked and Autosomal Recessive Alport Syndrome

DEFF Research Database (Denmark)

Savige, Judith; Storey, Helen; Il Cheong, Hae

2016-01-01

Alport syndrome results from mutations in the COL4A5 (X-linked) or COL4A3/COL4A4 (recessive) genes. This study examined 754 previously- unpublished variants in these genes from individuals referred for genetic testing in 12 accredited diagnostic laboratories worldwide, in addition to all published...... COL4A5, COL4A3 and COL4A4 variants in the LOVD databases. It also determined genotype-phenotype correlations for variants where clinical data were available. Individuals were referred for genetic testing where Alport syndrome was suspected clinically or on biopsy (renal failure, hearing loss...

A three-year-old boy with X-linked adrenoleukodystrophy and congenital pulmonary adenomatoid malformation: a case report

Directory of Open Access Journals (Sweden)

Cakan Nedim

2009-12-01

Full Text Available Abstract Introduction X-linked adrenoleukodystrophy leads to demyelination of the nervous system, adrenal insufficiency, and accumulation of long-chain fatty acids. Most young patients with X-linked adrenoleukodystrophy develop seizures and progressive neurologic deficits, and die within the first two decades of life. Congenital or acquired disorders of the respiratory system have not been previously described in patients with X-linked adrenoleukodystrophy. Case presentation A 3-year-old Arabic boy from Yemen presented with discoloration of the mucous membranes and nail beds, which were considered cyanoses due to methemoglobinemia. He also had shortness of breath, fatigue, emesis and dehydration episodes for which he was admitted to our hospital. Chest radiograph and chest computed tomography scans showed congenital pulmonary adenomatoid malformation. A few weeks before the removal of the malformation, he had a significant episode of hypotension and hypoglycemia. This development required further in-hospital evaluation that led to the diagnosis of adrenal insufficiency and the initiation of treatment with corticosteroids. One year later, he developed seizures and loss of consciousness. Magnetic resonance imaging of his head showed diffuse demyelination secondary to X-linked adrenoleukodystrophy. He was treated with anti-seizure and anti-oxidants, and was referred for bone marrow transplant evaluation. Conclusion The presence of adrenal insufficiency, neurologic deficits and seizures are common manifestations of X-linked adrenoleukodystrophy. The association of congenital lung disease with X-linked adrenoleukodystrophy or Addison's disease has not been described previously.

X-Linked Creatine Transporter Deficiency Presenting as a Mitochondrial Disorder

NARCIS (Netherlands)

Hathaway, S.C.; Friez, M.; Limbo, K.; Parker, C.; Salomons, G.S.; Vockley, J.; Wood, T.; Abdul-Rahman, O.A.

2010-01-01

X-linked creatine transporter defect is caused by mutations in SLC6A8 at Xq28, which encodes the sodium-dependent creatine transporter. Reduction in creatine uptake results in elevated urine creatine and CSF creatine deficiency, which can be detected on magnetic resonance spectroscopy. We report a

Faster-X evolution: Theory and evidence from Drosophila.

Science.gov (United States)

Charlesworth, Brian; Campos, José L; Jackson, Benjamin C

2018-02-12

A faster rate of adaptive evolution of X-linked genes compared with autosomal genes can be caused by the fixation of recessive or partially recessive advantageous mutations, due to the full expression of X-linked mutations in hemizygous males. Other processes, including recombination rate and mutation rate differences between X chromosomes and autosomes, may also cause faster evolution of X-linked genes. We review population genetics theory concerning the expected relative values of variability and rates of evolution of X-linked and autosomal DNA sequences. The theoretical predictions are compared with data from population genomic studies of several species of Drosophila. We conclude that there is evidence for adaptive faster-X evolution of several classes of functionally significant nucleotides. We also find evidence for potential differences in mutation rates between X-linked and autosomal genes, due to differences in mutational bias towards GC to AT mutations. Many aspects of the data are consistent with the male hemizygosity model, although not all possible confounding factors can be excluded. © 2018 John Wiley & Sons Ltd.

Multipoint linkage analysis and homogeneity tests in 15 Dutch X-linked retinitis pigmentosa families

NARCIS (Netherlands)

Bergen, A. A.; van den Born, L. I.; Schuurman, E. J.; Pinckers, A. J.; van Ommen, G. J.; Bleekers-Wagemakers, E. M.; Sandkuijl, L. A.

1995-01-01

Linkage analysis and homogeneity tests were carried out in 15 Dutch families segregating X-linked retinitis pigmentosa (X L R P). The study included segregation data for eight polymorphic DNA markers from the short arm of the human X chromosome. The results of both multipoint linkage analysis in

Non-syndromic posterior lenticonus a cause of childhood cataract: evidence for X-linked inheritance.

Science.gov (United States)

Russell-Eggitt, I M

2000-12-01

When an X-linked pedigree of posterior lenticonus with cataract was identified further evidence for X-linked inheritance of this condition was sought. Forty-three cases of posterior lenticonus were identified from a database of 354 children with cataract. Two children with the X-linked syndromes of Lowe and Nance-Horan and 3 children with Fanconi syndrome have been excluded from further analysis. None of the children was deaf. None of the non-syndromic cases had microcornea. There were 38 cases of non-syndromic posterior lenticonus (approximately 11%). There were 15 children from 13 pedigrees and 23 apparently sporadic cases. Of the 106 cases on the database with unilateral cataract 15 had posterior lenticonus (approximately 14%). Eleven of 13 pedigrees were compatible with X-linked inheritance or autosomal dominant inheritance with variable expression. However, in 2 pedigrees there was father to son transmission. Posterior lenticonus is a common cause of unilateral infantile cataract, but is thought to be a rare cause of bilateral cataracts. This study suggests that posterior lenticonus is responsible for a significant proportion of childhood cataracts (approximately 14% of unilateral and approximately 9% of bilateral cases). Posterior lenticonus is generally thought to occur as a sporadic condition. This study demonstrates that there is a family history of early-onset cataract in a significant number of bilateral cases (approximately 58%).

Genotype-phenotype variations in five Spanish families with Norrie disease or X-linked FEVR.

Science.gov (United States)

Riveiro-Alvarez, Rosa; Trujillo-Tiebas, Maria José; Gimenez-Pardo, Ascension; Garcia-Hoyos, Maria; Cantalapiedra, Diego; Lorda-Sanchez, Isabel; Rodriguez de Alba, Marta; Ramos, Carmen; Ayuso, Carmen

2005-09-02

Norrie disease (OMIM 310600) is a rare X-linked disorder characterized by congenital blindness in males. Approximately 40 to 50% of the cases develop deafness and mental retardation. X-linked familial exudative vitreoretinopathy (XL-FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Both X-linked disorders are due to mutations in the NDP gene, which encodes a 133 amino acid protein called Norrin, but autosomal recessive (AR) and autosomal dominant (AD) forms of FEVR have also been described. In this study, we report the molecular findings and the related phenotype in five Spanish families affected with Norrie disease or XL-FEVR due to mutations of the NDP gene. The study was conducted in 45 subjects from five Spanish families. These families were clinically diagnosed with Norrie disease or similar conditions. The three exons of the NDP gene were analyzed by automatic DNA sequencing. Haplotype analyses were also performed. Two new nonsense mutations, apart from other mutations previously described in the NDP gene, were found in those patients affected with ND or X-linked FEVR. An important genotype-phenotype variation was found in relation to the different mutations of the NDP gene. In fact, the same mutation may be responsible for different phenotypes. We speculate that there might be other molecular factors that interact in the retina with Norrin, which contribute to the resultant phenotypes.

Skin barrier properties in patients with recessive X-linked ichthyosis

DEFF Research Database (Denmark)

Johansen, J D; Ramsing, D; Vejlsgaard, G

1995-01-01

Patients with X-linked recessive ichthyosis (RXLI) were studied as a model of the effect of disturbed epidermal lipid composition on skin barrier function. Thirteen patients with RXLI and 15 age- and sex-matched controls were patch-tested with sodium lauryl sulphate (SLS) 0.5% for 24 h. Basal skin...

The Nance-Horan syndrome: a rare X-linked ocular-dental trait with expression in heterozygous females.

Science.gov (United States)

Bixler, D; Higgins, M; Hartsfield, J

1984-07-01

This report describes two families with the Nance-Horan syndrome, an X-linked trait featuring lenticular cataracts and anomalies of tooth shape and number. Previous reports have described blindness in affected males but posterior sutural cataracts with normal vision as the primary ocular expression in heterozygous females. In one of these two families, the affected female is not only blind in one eye but reportedly had supernumerary central incisors (mesiodens) removed. This constitutes the most severe ocular and dental expression of this gene in heterozygous females yet reported.

Woman with x-linked recessive dystonia-parkinsonism: clue to the epidemiology of parkinsonism in Filipino women?

Science.gov (United States)

Domingo, Aloysius; Lee, Lillian V; Brüggemann, Norbert; Freimann, Karen; Kaiser, Frank J; Jamora, Roland D G; Rosales, Raymond L; Klein, Christine; Westenberger, Ana

2014-09-01

Despite recessive inheritance, X-linked dystonia-parkinsonism (Lubag disease) has also been described in women presenting with a late-onset isolated parkinsonian syndrome. Interestingly, unlike in other populations, there is a slight female predominance in the prevalence of parkinsonism in the Philippines. In a Filipino woman with suspected Parkinson disease, we confirmed the presence of all changes specific for X-linked dystonia-parkinsonism in genomic DNA. Subsequently, we analyzed complementary DNA and evaluated the methylation status of the androgen receptor gene. Owing to extremely skewed (98%:2%) X-chromosome inactivation, the patient expressed almost solely the mutated allele in a disease-specific change, rendering her molecularly comparable with a hemizygously affected man. Skewed X-chromosome inactivation is the likely cause of parkinsonism in this heterozygous mutation carrier. Because women carriers of the genetic changes specific for X-linked dystonia-parkinsonism are common in the Philippines, the epigenetic factor of nonrandom X-chromosome inactivation may contribute to the skewing of the sex prevalence of parkinsonism toward women in this country, warranting further investigation.

Combination of supramolecular cross-linking with covalent cross-linking through epoxide ring-opening including gel studies

NARCIS (Netherlands)

Hofmeier, H.; El-Ghayoury, A.; Schubert, U.S.

2003-01-01

Terpolymers based on poly(methyl methacrylate), containing terpyridinemoieties as well as epoxide groups, were synthesized via free-radical polymerization. The products were cross-linked non-covalently with iron(II) ions and covalently by treatment with AlCl3. Both steps could be combined in

Normalized burn ratios link fire severity with patterns of avian occurrence

Science.gov (United States)

Rose, Eli T.; Simons, Theodore R.; Klein, Rob; McKerrow, Alexa

2016-01-01

ContextRemotely sensed differenced normalized burn ratios (DNBR) provide an index of fire severity across the footprint of a fire. We asked whether this index was useful for explaining patterns of bird occurrence within fire adapted xeric pine-oak forests of the southern Appalachian Mountains.ObjectivesWe evaluated the use of DNBR indices for linking ecosystem process with patterns of bird occurrence. We compared field-based and remotely sensed fire severity indices and used each to develop occupancy models for six bird species to identify patterns of bird occurrence following fire.MethodsWe identified and sampled 228 points within fires that recently burned within Great Smoky Mountains National Park. We performed avian point counts and field-assessed fire severity at each bird census point. We also used Landsat™ imagery acquired before and after each fire to quantify fire severity using DNBR. We used non-parametric methods to quantify agreement between fire severity indices, and evaluated single season occupancy models incorporating fire severity summarized at different spatial scales.ResultsAgreement between field-derived and remotely sensed measures of fire severity was influenced by vegetation type. Although occurrence models using field-derived indices of fire severity outperformed those using DNBR, summarizing DNBR at multiple spatial scales provided additional insights into patterns of occurrence associated with different sized patches of high severity fire.ConclusionsDNBR is useful for linking the effects of fire severity to patterns of bird occurrence, and informing how high severity fire shapes patterns of bird species occurrence on the landscape.

Increased insula-putamen connectivity in X-linked dystonia-parkinsonism

Directory of Open Access Journals (Sweden)

Anne J. Blood

2018-01-01

Full Text Available Preliminary evidence from postmortem studies of X-linked dystonia-parkinsonism (XDP suggests tissue loss may occur first and/or most severely in the striatal striosome compartment, followed later by cell loss in the matrix compartment. However, little is known about how this relates to pathogenesis and pathophysiology. While MRI cannot visualize these striatal compartments directly in humans, differences in relative gradients of afferent cortical connectivity across compartments (weighted toward paralimbic versus sensorimotor cortex, respectively can be used to infer potential selective loss in vivo. In the current study we evaluated relative connectivity of paralimbic versus sensorimotor cortex with the caudate and putamen in 17 individuals with XDP and 17 matched controls. Although caudate and putamen volumes were reduced in XDP, there were no significant reductions in either “matrix-weighted”, or “striosome-weighted” connectivity. In fact, paralimbic connectivity with the putamen was elevated, rather than reduced, in XDP. This was driven most strongly by elevated putamen connectivity with the anterior insula. There was no relationship of these findings to disease duration or striatal volume, suggesting insula and/or paralimbic connectivity in XDP may develop abnormally and/or increase in the years before symptom onset.

Combination of supramolecular cross-linking with covalent cross-linking through epoxide ring-opening including gel studies

NARCIS (Netherlands)

Hofmeier, H.; El-Ghayoury, A.; Schubert, U.S.

2003-01-01

Terpolymers based on poly(methyl methacrylate), containing terpyridine-moieties as well as epoxide groups, were synthesized via free-radical polymeri-zation. The products were cross-linked non-covalently with iron(II) ions and cova-lently by treatment with AlCl3. Both steps could be combined in

Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects

NARCIS (Netherlands)

A.F. Daly (Adrian); B. Yuan (Bo); Fina, F. (Frederic); J.-H. Caberg (Jean-Hubert); G. Trivellin (Giampaolo); L. Rostomyan (Liliya); W.W. de Herder (Wouter); L.A. Naves (Lucianna); D. Metzger (Daniel); T. Cuny (Thomas); Rabl, W. (Wolfgang); N.S. Shah (Nalini Samir); M-L. Jaffrain-Rea (Marie-Lise); Chiara Zatelli, M. (Maria); F.R. Faucz (Fabio R.); E. Castermans (Emilie); Nanni-Metellus, I. (Isabelle); Lodish, M. (Maya); A. Muhammad (Ammar); Palmeira, L. (Leonor); Potorac, I. (Iulia); G. Mantovani (Giovanna); S.J.C.M.M. Neggers (Bas); Klein, M. (Marc); A. Barlier (Anne); P. Liu (Pengfei); Ouafik, L. (L'houcine); V. Bours (Vincent); Lupski, J.R. (James R.); C.A. Stratakis (Constantine); A. Beckers (Albert)

2016-01-01

textabstractSomatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG)syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic

[Clinical and molecular study in a child with X-linked hypohidrotic ectodermal dysplasia].

Science.gov (United States)

Callea, Michele; Yavuz, Izzet; Clarich, Gabriella; Cammarata-Scalisi, Francisco

2015-12-01

Ectodermal dysplasia encompasses more than 200 clinically distinct entities, which affect at least two structures derived from the ectoderm, including the skin, hair, nails, teeth, sweat glands, and sebaceous glands. X-linked hypohidrotic ectodermal dysplasia is the most common type and is caused by mutation of the EDA gene that encodes Ectodysplasin-A. It occurs in less than 1 in 100 000 individuals and is clinically characterized by hypodontia, hypohidrosis, hypotrichosis, and eye dis orders. We present a child evaluated in a multidisciplinary manner with clinical and molecular diagnosis of X-linked hypohidrotic ectodermal dysplasia with type missense mutation c.1133C> T; p.T378M in EDA gene.

X-linked Myotubular Myopathy with a Novel MTM1 Mutation in a Taiwanese Child

Directory of Open Access Journals (Sweden)

Chia-Ying Chang

2008-12-01

Full Text Available We report a male, preterm newborn infant with X-linked myotubular myopathy, the most severe type of the disease. He presented at birth with generalized hypotonia, difficulty in swallowing, and respiratory distress with frequent episodes of atelectasis. The infant had a long thin face, generalized hypotonia, and arachnodactyly. Diagnosis was based on fetal history, muscle histopathology, electron microscopy and a genetic study. A base pair change was detected in exon 11 of the MTM1 gene: c.1160C > A, which caused an amino acid change, p.S387Y. The father's gene was normal but the mother had the same mutation as her son and was thus a carrier.

X-linked adrenal hypoplasia congenita: a case report and ethical dilemma.

Science.gov (United States)

Ismail, Heba M; Rincon, Marielisa

2014-07-01

Our objective is to present the first case report of X-linked adrenal hypoplasia congenita in a child conceived by a donated egg and which also presented atypically, with initial mineralocorticoid deficiency. Case report with literature review. A late preterm fraternal twin male, conceived by in vitro fertilization of donated eggs, presented shortly after birth with feeding intolerance, hyponatremia, and hyperkalemia. Testing revealed a low aldosterone level, high plasma renin activity, normal cortisol level, and normal 17-hydroxyprogesterone level. He was diagnosed with 18-hydroxylase deficiency based on low 18-hydroxycorticosterone levels and was treated with mineralocorticoid successfully for 17 months. At age 18 months, he presented with dehydration secondary to herpetic gingivostomatitis and was found to be hypoglycemic, hyponatremic, hyperkalemic, and acidotic, with a low serum cortisol level. An adrenocorticotropic hormone (ACTH) stimulation test revealed low levels of all adrenal cortex products, with an elevated ACTH level. He was started on glucocorticoids. Genetic testing confirmed X-linked adrenal hypoplasia congenita (AHC). His asymptomatic fraternal twin underwent genetic testing and the results were negative. The fertility center records indicated that the mother had donated eggs to other families, but none of the children were known to have this disorder. The egg donor was informed but did not pursue genetic testing. We report a case of X-linked AHC presenting in the context of extraordinary ethical considerations. Our case raises a question unique to the era of assisted reproduction: should routine genetic screening of gamete donors be done for rare but potentially life-threatening conditions?

Expanding phenotype of p.Ala140Val mutation in MECP2 in a 4 generation family with X-linked intellectual disability and spasticity.

Science.gov (United States)

Lambert, Sophie; Maystadt, Isabelle; Boulanger, Sébastien; Vrielynck, Pascal; Destrée, Anne; Lederer, Damien; Moortgat, Stéphanie

2016-10-01

Mutations in MECP2 (MIM #312750), located on Xq28 and encoding a methyl CpG binding protein, are classically associated with Rett syndrome in female patients, with a lethal effect in hemizygous males. However, MECP2 mutations have already been reported in surviving males with severe neonatal-onset encephalopathy, or with X-linked intellectual disability associated with psychosis, pyramidal signs, parkinsonian features and macro-orchidism (PPM-X syndrome; MIM3 #300055). Here we report on the identification of the p.Ala140Val mutation in the MECP2 gene in 4 males and 3 females of a large Caucasian family affected with X-linked intellectual disability. Females present with mild cognitive impairment and speech difficulties. Males have moderate intellectual disability, impaired language development, friendly behavior, slowly progressive spastic paraparesis and dystonic movements of the hands. Two of them show microcephaly. The p.Ala140Val mutation is recurrent, as it was already described in 4 families with X-linked mental retardation and in three sporadic male patients with intellectual disability. We further delineate the phenotype associated with the p.Ala140Val mutation, illustrating a variable expressivity even within a given family, and we compare our patients with previous reported cases in the literature. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Screening for severe combined immunodeficiency in neonates

OpenAIRE

Kelly, Brian T; Tam, Jonathan S; Verbsky, James W; Routes, John M

2013-01-01

Brian T Kelly,1 Jonathan S Tam,1 James W Verbsky,1,2 John M Routes1,2 1Department of Pediatrics, 2Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA Abstract: Severe combined immunodeficiency (SCID) is a rare disease that severely affects the cellular and humoral immune systems. Patients with SCID present with recurrent or severe infections and often with chronic diarrhea and failure to thrive. The disease is uniformly fatal, making early diag...

Severe combined immune deficiency syndrome

International Nuclear Information System (INIS)

Saleem, A.F.; Khawaja, R.D.A.; Shaikh, A.S.; Ali, S.A.; Zaidi, A.K.M.

2013-01-01

To determine the clinico-demographic features and laboratory parameters of children with severe combined immunodeficiency (SCID). Study Design: Case series. Place and Duration of Study: Department of Paediatrics and Child Health, the Aga Khan University, Karachi, from July 2006 to July 2011. Methodology: Thirteen infants who were discharged with a diagnosis of SCID were inducted in the study. Their clinicodemographic features and laboratory parameters were determined. Descriptive statistics has been used for computing frequency and percentage. Results: The median age at diagnosis was five months; 5 infants presented within 3 months of life. Three-fourth (77%) were males. Most of the infants were severely malnourished (85%) at the time of presentation. More than two-thirds (69%) were products of consanguineous marriages. All subjects had severe lymphopenia (absolute lymphocyte count (ALC) ranging between 170 – 2280) and low T and B lymphocyte counts. Conclusion: SCID should be considered in infants presenting with severe and recurrent infections. Low ALC (< 2500/mm3), is a reliable diagnostic feature of SCID. These infants should be promptly referred to a facility where stem cell transplant can be done. (author)

X-linked lethal infantile spinal muscular atrophy: From clinical description to molecular mapping

Energy Technology Data Exchange (ETDEWEB)

Baumbach, L.; Schiavi, A. [Univ. of Miami, FL (United States)] [and others

1994-09-01

The proximal spinal muscular atrophies (PSMA), one of the most common forms of lower motor neuron disease in children, are characterized by progressive muscle weakness due to loss of anterior horn cells. All three autosomal recessive forms have been mapped to chromosome 5q11.2-11.3, implying an allelic association between these disorders. Recent evidence from our laboratories, as well as others, suggests that a distinct form of lethal neonatal spinal muscular atrophy, associated with early onset contractures, is determined by a gene on the X chromosome. We report our efforts in mapping this disease locus. Our original studies have focused on two unrelated multigenerational families with similar clinical presentations of severe hypotonia, muscle weakness, and a disease course similar to Werdnig Hoffman except for the additional finding of congenital or early onset contractures. Muscle biopsy and/or autopsy were indicative of anterior horn cell loss in affected males. Disease occurrence in each of the families was consistent with an X-linked recessive mode of inheritance. Subsequently, two additional families have been identified, as well as several sporadic male cases. Linkage analysis has been completed in one of these families using highly polymorphic repeats dispersed 10 cM on the X chromosome. Interpretation of results was achieved using an automated data acquisition program. Analysis of over 300 haplotypes generated using PCR-based DNA markers have identified two 16 cM regions on Xp with complete concordance to the disease phenotype. Our currents efforts are focused on the region surrounding the Kallman gene, in attempts to better define a candidate region, as well as analyze possible candidate genes within this region.

The rapid evolution of X-linked male-biased gene expression and the large-X effect in Drosophila yakuba, D. santomea, and their hybrids.

Science.gov (United States)

Llopart, Ana

2012-12-01

The X chromosome has a large effect on hybrid dysfunction, particularly on hybrid male sterility. Although the evidence for this so-called large-X effect is clear, its molecular causes are not yet fully understood. One possibility is that, under certain conditions, evolution proceeds faster in X-linked than in autosomal loci (i.e., faster-X effect) due to both natural selection and their hemizygosity in males, an effect that is expected to be greatest in genes with male-biased expression. Here, I study genome-wide variation in transcript abundance between Drosophila yakuba and D. santomea, within these species and in their hybrid males to evaluate both the faster-X and large-X effects at the level of expression. I find that in X-linked male-biased genes (MBGs) expression evolves faster than in their autosomal counterparts, an effect that is accompanied by a unique reduction in expression polymorphism. This suggests that Darwinian selection is driving expression differences between species, likely enhanced by the hemizygosity of the X chromosome in males. Despite the recent split of the two sister species under study, abundant changes in both cis- and trans-regulatory elements underlie expression divergence in the majority of the genes analyzed, with significant differences in allelic ratios of transcript abundance between the two reciprocal F(1) hybrid males. Cis-trans coevolution at molecular level, evolved shortly after populations become isolated, may therefore contribute to explain the breakdown of the regulation of gene expression in hybrid males. Additionally, the X chromosome plays a large role in this hybrid male misexpression, which affects not only MBG but also, to a lesser degree, nonsex-biased genes. Interestingly, hybrid male misexpression is concentrated mostly in autosomal genes, likely facilitated by the rapid evolution of sex-linked trans-acting factors. I suggest that the faster evolution of X-linked MBGs, at both protein and expression levels

+2.71 LOD score at zero recombination is not sufficient for establishing linkage between X-linked mental retardation and X-chromosome markers

Energy Technology Data Exchange (ETDEWEB)

Robledo, R.; Melis, P.; Siniscalco, M. [and others

1996-07-12

Nonspecific X-linked mental retardation (MRX) is the denomination attributed to the familial type of mental retardation compatible with X-linked inheritance but lacking specific phenotypic manifestations. It is thus to be expected that families falling under such broad definition are genetically heterogeneous in the sense that they may be due to different types of mutations occurring, most probably, at distinct X-chromosome loci. To facilitate a genetic classification of these conditions, the Nomenclature Committee of the Eleventh Human Gene Mapping Workshop proposed to assign a unique MRX-serial number to each family where evidence of linkage with one or more X-chromosome markers had been established with a LOD score of at least +2 at zero recombination. This letter is meant to emphasize the inadequacy of this criterion for a large pedigree where the segregation of the disease has been evaluated against the haplotype constitution of the entire X-chromosome carrying the mutation in question. 12 refs., 2 figs., 1 tab.

X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene.

Science.gov (United States)

Lagresle-Peyrou, Chantal; Luce, Sonia; Ouchani, Farid; Soheili, Tayebeh Shabi; Sadek, Hanem; Chouteau, Myriam; Durand, Amandine; Pic, Isabelle; Majewski, Jacek; Brouzes, Chantal; Lambert, Nathalie; Bohineust, Armelle; Verhoeyen, Els; Cosset, François-Loïc; Magerus-Chatinet, Aude; Rieux-Laucat, Frédéric; Gandemer, Virginie; Monnier, Delphine; Heijmans, Catherine; van Gijn, Marielle; Dalm, Virgil A; Mahlaoui, Nizar; Stephan, Jean-Louis; Picard, Capucine; Durandy, Anne; Kracker, Sven; Hivroz, Claire; Jabado, Nada; de Saint Basile, Geneviève; Fischer, Alain; Cavazzana, Marina; André-Schmutz, Isabelle

2016-12-01

We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections. We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency. We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment. We observed hemizygous mutations in the moesin (MSN) gene (located on the X chromosome and coding for MSN) in all 7 patients. Six of the latter had the same missense mutation, which led to an amino acid substitution (R171W) in the MSN four-point-one, ezrin, radixin, moesin domain. The seventh patient had a nonsense mutation leading to a premature stop codon mutation (R533X). The naive T-cell counts were particularly low for age, and most CD8 + T cells expressed the senescence marker CD57. This phenotype was associated with impaired T-cell proliferation, which was rescued by expression of wild-type MSN. MSN-deficient T cells also displayed poor chemokine receptor expression, increased adhesion molecule expression, and altered migration and adhesion capacities. Our observations establish a causal link between an ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects.

Science.gov (United States)

Daly, Adrian F; Yuan, Bo; Fina, Frederic; Caberg, Jean-Hubert; Trivellin, Giampaolo; Rostomyan, Liliya; de Herder, Wouter W; Naves, Luciana A; Metzger, Daniel; Cuny, Thomas; Rabl, Wolfgang; Shah, Nalini; Jaffrain-Rea, Marie-Lise; Zatelli, Maria Chiara; Faucz, Fabio R; Castermans, Emilie; Nanni-Metellus, Isabelle; Lodish, Maya; Muhammad, Ammar; Palmeira, Leonor; Potorac, Iulia; Mantovani, Giovanna; Neggers, Sebastian J; Klein, Marc; Barlier, Anne; Liu, Pengfei; Ouafik, L'Houcine; Bours, Vincent; Lupski, James R; Stratakis, Constantine A; Beckers, Albert

2016-04-01

Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101 We studied XLAG syndrome patients (n= 18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2ratio (LR) compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8%. These characteristics were replicated using a novel, personalized breakpoint junction-specific quantification droplet digital polymerase chain reaction (ddPCR) technique. Using a separate ddPCR technique, we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism, and identified one female gigantism patient who had had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes. © 2016 Society for Endocrinology.

A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation

DEFF Research Database (Denmark)

Kleine-Kohlbrecher, Daniela; Christensen, Jesper; Vandamme, Julien

2010-01-01

X-linked mental retardation (XLMR) is an inherited disorder that mostly affects males and is caused by mutations in genes located on the X chromosome. Here, we show that the XLMR protein PHF8 and a C. elegans homolog F29B9.2 catalyze demethylation of di- and monomethylated lysine 9 of histone H3 (H......3K9me2/me1). The PHD domain of PHF8 binds to H3K4me3 and colocalizes with H3K4me3 at transcription initiation sites. Furthermore, PHF8 interacts with another XMLR protein, ZNF711, which binds to a subset of PHF8 target genes, including the XLMR gene JARID1C. Of interest, the C. elegans PHF8 homolog...... is highly expressed in neurons, and mutant animals show impaired locomotion. Taken together, our results functionally link the XLMR gene PHF8 to two other XLMR genes, ZNF711 and JARID1C, indicating that MR genes may be functionally linked in pathways, causing the complex phenotypes observed in patients...

Substitution rates in the X- and Y-linked genes of the plants, Silene latifolia and S. dioica.

Science.gov (United States)

Filatov, Dmitry A; Charlesworth, Deborah

2002-06-01

Theory predicts that selection should be less effective in the nonrecombining genes of Y-chromosomes, relative to the situation for genes on the other chromosomes, and this should lead to the accumulation of deleterious nonsynonymous substitutions. In addition, synonymous substitution rates may differ between X- and Y-linked genes because of the male-driven evolution effect and also because of actual differences in per-replication mutation rates between the sex chromosomes. Here, we report the first study of synonymous and nonsynonymous substitution rates on plant sex chromosomes. We sequenced two pairs of sex-linked genes, SlX1-SlY1 and SlX4-SlY4, from dioecious Silene latifolia and S. dioica, and their non-sex-linked homologues from nondioecious S. vulgaris and Lychnis flos-jovis, respectively. The rate of nonsynonymous substitutions in the SlY4 gene is significantly higher than that in the SlX4 gene. Silent substitution rates are also significantly higher in both Y-linked genes, compared with their X-linked homologues. The higher nonsynonymous substitution rate in the SlY4 gene is therefore likely to be caused by a mutation rate difference between the sex chromosomes. The difference in silent substitution rates between the SlX4 and SlY4 genes is too great to be explained solely by a higher per-generation mutation rate in males than females. It is thus probably caused by a difference in per-replication mutation rates between the sex chromosomes. This suggests that the local mutation rate can change in a relatively short evolutionary time.

JS-X syndrome: A multiple congenital malformation with vocal cord paralysis, ear deformity, hearing loss, shoulder musculature underdevelopment, and X-linked recessive inheritance.

Science.gov (United States)

Hoeve, Hans L J; Brooks, Alice S; Smit, Liesbeth S

2015-07-01

We report on a family with a not earlier described multiple congenital malformation. Several male family members suffer from laryngeal obstruction caused by bilateral vocal cord paralysis, outer and middle ear deformity with conductive and sensorineural hearing loss, facial dysmorphisms, and underdeveloped shoulder musculature. The affected female members only have middle ear deformity and hearing loss. The pedigree is suggestive of an X-linked recessive inheritance pattern. SNP-array revealed a deletion and duplication on Xq28 in the affected family members. A possible aetiology is a neurocristopathy with most symptoms expressed in structures derived from branchial arches. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

High bone mineral apparent density in children with X-linked hypophosphatemia

DEFF Research Database (Denmark)

Beck-Nielsen, Signe; Brixen, K; Gram, J

2013-01-01

of the spine compared to femoral neck. INTRODUCTION: BMAD obtained by dual-energy X-ray absorptiometry scans in children with XLH was evaluated, as they are unlikely to have the extra-skeletal ossifications contributing to the elevated bone mineral density of the spine in adult patients. METHODS: A total of 15......Bone mineral apparent density (BMAD) in children with X-linked hypophosphatemia (XLH) was evaluated, as they are unlikely to have extra-skeletal ossifications contributing to the elevated bone mineral density of the spine in adult patients. Children with XLH also had significantly higher BMAD...

Effects of combined heat and x-rays on tumours in mice

International Nuclear Information System (INIS)

Hill, S.A.

1980-08-01

The therapeutic potential of combined hyperthermia and radiation was investigated in six different types of experimental mouse tumour. Their response to hyperthermia alone and combined heat and X-ray treatments was assessed by delay in tumour regrowth. Thermal sensitivity was found to vary from tumour to tumour. The importance of the order of application and the time interval between treatments was investigated, and the tumour response compared with that of mouse skin as an example of a normal tissue. A therapeutic gain was not seen for X-rays and heat in close sequence. It was however seen when heat was applied several hours after irradiation. Constriction of the tumour blood supply, either artificially, or naturally by implantation into a constricted site, was found to increase thermal sensitivity dramatically. Possible reasons for this are discussed. Heat applied immediately before irradiation may result in a small increase in metastatic spread. Heat applied at other times did not influence the metastatic incidence. Immersion in hot water was examined as a method of heating experimental mouse tumours, and was found to be inadequate in terms of the temperature uniformity achieved. The influence of this factor on results using water bath heating are discussed. (author)

X-Linked Dystonia Parkinsonism: Clinical Phenotype, Genetics and Therapeutics

Directory of Open Access Journals (Sweden)

Raymond L. Rosales

2010-10-01

Full Text Available The clinical phenotype of X-Linked Dystonia Parkinsonism (XDP is typically one that involves a Filipino adult male whose ancestry is mostly traced in the Philippine island of Panay. Dystonia usually starts focally in the lower limbs or oromandibular regions, then spreads to become generalized eventually. Parkinsonism sets in later into the disease and usually in combination with dystonia. /DYT3/ and /TAF1/ are the two genes associated with XDP. An SVA retrotransposon insertion in an intron of /TAF1/ may reduce neuron-specific expression of the /TAF1/ isoform in the caudate nucleus, and subsequently interfere with the transcription of many neuronal genes. Polypharmacy with oral benzodiazepines, anticholinergic agents and muscle relaxants leaves much to be desired in terms of efficacy. The medications to date that may appear beneficial, especially in disabling dystonias, are zolpidem, muscle afferent block with lidocaine-ethanol and botulinum toxin type A. Despite the few cases undergoing deep brain stimulation, this functional surgery has shown the greatest promise in XDP. An illustrative case of XDP in a family depicts the variable course of illness, including a bout of “status dystonicus,” challenges in therapy, reckoning with the social impact of the disease, and eventual patient demise. Indeed, there remains some gaps in understanding some phenomenological, genetic and treatment aspects of XDP, the areas upon which future research directions may be worthwhile.

X-linked recessive primary retinal dysplasia is linked to the Norrie disease locus.

Science.gov (United States)

Ravia, Y; Braier-Goldstein, O; Bat-Miriam, K M; Erlich, S; Barkai, G; Goldman, B

1993-08-01

X-linked primary retinal dysplasia (PRD) refers to an abnormal proliferation of retinal tissue causing either its neural elements or its glial tissue to form folds, giving rise to gliosis. A Jewish family of oriental origin was previously reported by Godel and Goodman, in which a total of five males suffer from different degrees of blindness. The authors postulated that the described findings are distinguished from Norrie disease, since in this case no clinical findings, other than those associated with the eyes, were noticed in the affected males. In addition, two of the carrier females exhibit minimal eye changes. We have performed linkage analysis of the family using the L1.28, p58-1 and m27 beta probes, and DXS426 and MAOB associated microsatellites. Our results map the gene responsible for the disorder between the MAOB and DXS426, m27 beta and p58-1 loci, on the short arm of the X chromosome at Xp11.3, which suggest the possibility that the same gene is responsible for both primary retinal dysplasia and Norrie disease.

Germline but macrophage-tropic CYBB mutations in kindreds with X-linked predisposition to tuberculous mycobacterial diseases

OpenAIRE

2011-01-01

Abstract Germline mutations in the human CYBB gene, encoding the gp91phox subunit of the phagocyte NADPH oxidase, impair the respiratory burst of phagocytes and result in X-linked chronic granulomatous disease. We report two kindreds in which otherwise healthy male adults show X-linked recessive Mendelian susceptibility to mycobacterial diseases. These patients harbor mutations in CYBB that profoundly reduce the respiratory burst in monocyte-derived macrophages, but not in monocyte...

[X-linked adrenoleukodystrophy: a report of three cases. The importance of early diagnosis].

Science.gov (United States)

López Úbeda, Marta; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José I; García Jiménez, María C

2017-10-01

X-linked adrenoleukodystrophy is the most common peroxisomal disorder. This disease is caused by a defect in the ABCD1 gen. Saturated very long chain fatty acids are accumulated in serum, adrenal cortex and central nervous system white matter. The clinical spectrum is characterized by progressive neurological dysfunction and adrenal insufficiency with a devastating prognosis. We report a first case of X-linked adrenoleukodystrophy with fatal evolution which identified two asymptomatic family members and established a preventive treatment. Although there is no definitive cure, we stress the importance of family study and evaluation of the individual in situation of risk to establish an early preventive treatment and to give in each particular situation suitable professional advice. Sociedad Argentina de Pediatría.

Patulous Subarachnoid Space of the Optic Nerve Associated with X-Linked Hypophosphatemic Rickets.

Science.gov (United States)

Galvez-Ruiz, Alberto; Chaudhry, Imtiaz

2013-01-01

Although the deficiency forms are the most common manifestations of rickets, there are other forms of rickets that are resistant to vitamin D. Of these, the most common is X-linked hypophosphatemic rickets. Rickets represents a group of multiple cranial bone disorders-craniosynostosis and the presence of Chari I malformation being the most notable-that explain the increase in intracranial pressure. We present a 4-year-old patient with an unusual association of X-linked hypophosphataemic rickets, bilateral proptosis, and prominent bilateral widening of the optic nerve sheaths. Although the association between intracranial hypertension and rickets is known, to the best of our knowledge, such a prominent distention of the subarachnoid space of the optic nerve without papilloedema has not been previously described.

Studies on combination effects of peplomycin and x-ray irradiation

International Nuclear Information System (INIS)

Munenaga, Yasuichi

1984-01-01

In order to study effects and methods of combination of peplomycin (PEP) and x-ray irradiation, inhibitory effects on DNA synthesis were investigated with synchronized cells from the parotid gland of mice treated with isoproterenol (IPR) and inhibitory effects on cell proliferation were investigated with Ehrlich solid tumor cells. PEP had dose-dependent effects on the inhibition of DNA synthesis and on the prolongation of cell cycles in the IPR-treated mouse cells. When 3.0 and 5.0 mg/kg of PEP were combined with 200 rad of x-ray irradiation at the early phase of G 1 , synergistic effects on the inhibition of DNA synthesis were seen. This was most noted in the group with PEP 30 minutes before irradiation. PEP had also dose-dependent inhibitory effects on the proliferation of Ehrlich solid tumor cells. This was increased when x-ray irradiation was combined with PEP. Inhibitory effects on the proliferation of tumor cells were greater when PEP was given before x-ray irradiation than after x-ray irradiation, regardless of the amount. The greatest effect was seen in the group with PEP 30 minutes before irradiation, as well as in the experiment with IPR-treated mouse cells. (Namekawa, K.)

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3). Combination effect on the metastatic tumors

Energy Technology Data Exchange (ETDEWEB)

Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-03-01

Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF/sub 1/ mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free.

MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

Science.gov (United States)

Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

2016-01-01

Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

Combining X-ray Absorption and X-ray Diffraction Techniques for in Situ Studies of Chemical Transformations in Heterogeneous Catalysis: Advantages and Limitations

International Nuclear Information System (INIS)

Frenkel, A.I.; Hanson, J.; Wang, Q.; Marinkovic, N.; Chen, J.G.; Barrio, L.; Si, R.; Lopez Camara, A.; Estrella, A.M.; Rodriguez, J.A.

2011-01-01

Recent advances in catalysis instrumentations include synchrotron-based facilities where time-resolved X-ray scattering and absorption techniques are combined in the same in situ or operando experiment to study catalysts at work. To evaluate the advances and limitations of this method, we performed a series of experiments at the new XAFS/XRD instrument in the National Synchrotron Light Source. Nearly simultaneous X-ray diffraction (XRD) and X-ray absorption fine-structure (XAFS) measurements of structure and kinetics of several catalysts under reducing or oxidizing conditions have been performed and carefully analyzed. For CuFe 2 O 4 under reducing conditions, the combined use of the two techniques allowed us to obtain accurate data on kinetics of nucleation and growth of metallic Cu. For the inverse catalyst CuO/CeO 2 that underwent isothermal reduction (with CO) and oxidation (with O 2 ), the XAFS data measured in the same experiment with XRD revealed strongly disordered Cu species that went undetected by diffraction. These and other examples emphasize the unique sensitivity of these two complementary methods to follow catalytic processes in the broad ranges of length and time scales.

Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects

NARCIS (Netherlands)

Bauters, M.; Frints, S.G.; Esch, H. van; Spruijt, L.; Baldewijns, M.M.; Die-Smulders, C.E.M. de; Fryns, J.P.; Marynen, P.; Froyen, G.

2014-01-01

Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from

X-linked mental retardation with neonatal hypotonia in a French family (MRX15): Gene assignment to Xp11.22-Xp21.1

Energy Technology Data Exchange (ETDEWEB)

Raynaud, M.; Dessay, B.; Ayrault, A.D. [INSERM, Marseille (France)] [and others

1996-07-12

Linkage analysis was performed in a family with non-specific X-linked mental retardation (MRX 15). Hypotonia in infancy was the most remarkable physical manifestation. The severity of mental deficiency was variable among the patients, but all of them had poor or absent speech. Significant lod scores at a recombination fraction of zero were detected with the marker loci DXS1126, DXS255, and DXS573 (Zmax = 2.01) and recombination was observed with the two flanking loci DXS164 (Xp21.1) and DXS988 (Xp11.22), identifying a 17 cM interval. This result suggests a new gene localization in the proximal Xp region. In numerous families with non-specific X-linked mental retardation (MRX), the corresponding gene has been localized to the paracentromeric region in which a low recombination rate impairs the precision of mapping. 58 refs., 3 figs., 5 tabs.

CRISPR/Cas9 Promotes Functional Study of Testis Specific X-Linked Gene In Vivo.

Directory of Open Access Journals (Sweden)

Minyan Li

Full Text Available Mammalian spermatogenesis is a highly regulated multistage process of sperm generation. It is hard to uncover the real function of a testis specific gene in vitro since the in vitro model is not yet mature. With the development of the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9 system, we can now rapidly generate knockout mouse models of testis specific genes to study the process of spermatogenesis in vivo. SYCP3-like X-linked 2 (SLX2 is a germ cell specific component, which contains a Cor1 domain and belongs to the XLR (X-linked, lymphocyte regulated family. Previous studies suggested that SLX2 might play an important role in mouse spermatogenesis based on its subcellular localization and interacting proteins. However, the function of SLX2 in vivo is still elusive. Here, to investigate the functions of SLX2 in spermatogenesis, we disrupted the Slx2 gene by using the CRISPR/Cas9 system. Since Slx2 is a testis specific X-linked gene, we obtained knockout male mice in the first generation and accelerated the study process. Compared with wild-type mice, Slx2 knockout mice have normal testis and epididymis. Histological observation of testes sections showed that Slx2 knockout affected none of the three main stages of spermatogenesis: mitosis, meiosis and spermiogenesis. In addition, we further confirmed that disruption of Slx2 did not affect the number of spermatogonial stem cells, meiosis progression or XY body formation by immunofluorescence analysis. As spermatogenesis was normal in Slx2 knockout mice, these mice were fertile. Taken together, we showed that Slx2 itself is not an essential gene for mouse spermatogenesis and CRISPR/Cas9 technique could speed up the functional study of testis specific X-linked gene in vivo.

Fatal hepatic hemorrhage by peliosis hepatis in X-linked myotubular myopathy: a case report.

Science.gov (United States)

Motoki, T; Fukuda, M; Nakano, T; Matsukage, S; Fukui, A; Akiyoshi, S; Hayashi, Y K; Ishii, E; Nishino, I

2013-11-01

We report a 5-year-old boy with X-linked myotubular myopathy complicated by peliosis hepatis. At birth, he was affected with marked generalized muscle hypotonia and weakness, which required permanent ventilatory support, and was bedridden for life. He died of acute fatal hepatic hemorrhage after using a mechanical in-exsufflator. Peliosis hepatis, defined as multiple, variable-sized, cystic blood-filled spaces through the liver parenchyma, was confirmed by autopsy. To avoid fatal hepatic hemorrhage by peliosis hepatis, routine hepatic function tests and abdominal imaging tests should be performed for patients with X-linked myotubular myopathy, especially at the time of using artificial respiration. Copyright © 2013 Elsevier B.V. All rights reserved.

X irradiation combined with TNF alpha-related apoptosis-inducing ligand (TRAIL) reduces hypoxic regions of human gastric adenocarcinoma xenografts in SCID mice

International Nuclear Information System (INIS)

Takahashi, Momoko; Yasui, Hironobu; Ogura, Aki; Asanuma, Taketoshi; Inanami, Osamu; Kubota, Nobuo; Tsujitani, Michihiko; Kuwabara, Mikinori

2008-01-01

Our previous study showed that X irradiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines under not only normoxia but also hypoxia. X irradiation combined with TNF α-related apoptosis-inducing ligand (TRAIL), which is the ligand of DR5, induced apoptosis in vitro (Takahashi et al., (2007) Journal of Radiation Research, 48: 461-468). In this report, we examined the in vivo antitumor efficacy of X irradiation combined with TRAIL treatment in tumor xenograft models derived from human gastric adenocarcinoma MKN45 and MKN28 cells in severe combined immunodeficiency (SCID) mice. X irradiation combined with TRAIL synergistically suppressed the tumor growth rates in the xenograft models derived from MKN45 and MKN28 cells, which have wild type Tp53 and mutated Tp53, respectively, indicating that the antitumor effects occurred in a Tp53-independent manner. Histological analysis showed that the combination of X irradiation and TRAIL induced caspase-3-dependent apoptotic cell death. Moreover, the immunohistochemical detection of hypoxic regions using the hypoxic marker pimonidazole revealed that caspase-3-dependent apoptosis occurred in the hypoxic regions in the tumors. These results indicated that X irradiation combined with TRAIL may be a useful treatment to reduce tumor growth in not only normoxic but also hypoxic regions. (author)

Clinical manifest x-linked recessive adrenoleukodystrophy in a female

DEFF Research Database (Denmark)

Jack, Gyda Hlin Skuladottir; Malm-Willadsen, Karolina; Frederiksen, Anja

2013-01-01

Adrenoleukodystrophy (ALD) is a rare X-linked inherited leukodystrophy with a reduced capacity for degradation of very long chain fatty acids (VLCFAs). The intracellular accumulation of VLCFA leads to demyelination in the central nervous system (CNS) and cell destruction in the adrenal glands. ALD...... examination revealed decreased sensitivity in the feet, particularly to touch. Deep tendon reflexes in the lower limbs were brisk, and Babinski's sign was present bilaterally. Multiple sclerosis (MS) was excluded, and all clinical and biochemical tests were normal. After two years of progressing symptoms...

X-linked ocular albinism in Blacks. Ocular albinism cum pigmento.

Science.gov (United States)

O'Donnell, F E; Green, W R; Fleischman, J A; Hambrick, G W

1978-07-01

X-linked ocular albinism can be an unsuspected cause of congenital nystagmus in blacks. In this study, eight of ten black ocular albinos from two kindreds had nonalbinotic, moderately pigmented fundi and no transillumination of the iris. We refer to this paradoxical condition as "ocular albinism cum pigmento." The only constant ophthalmoscopic feature was a foveal hypoplasia. Biopsy of clinically normal skin to demonstrate giant pigment granules is the most accurate means of diagnosis.

Somatic Mosaicism Underlies X-linked Acrogigantism (XLAG) Syndrome in Sporadic Male Subjects

Science.gov (United States)

Daly, Adrian F.; Yuan, Bo; Fina, Frederic; Caberg, Jean-Hubert; Trivellin, Giampaolo; Rostomyan, Liliya; de Herder, Wouter W.; Naves, Luciana A.; Metzger, Daniel; Cuny, Thomas; Rabl, Wolfgang; Shah, Nalini; Jaffrain-Rea, Marie-Lise; Zatelli, Maria Chiara; Faucz, Fabio R; Castermans, Emilie; Nanni-Metellus, Isabelle; Lodish, Maya; Muhammad, Ammar; Palmeira, Leonor; Potorac, Iulia; Mantovani, Giovanna; Neggers, Sebastian J.; Klein, Marc; Barlier, Anne; Liu, Pengfei; Ouafik, L'Houcine; Bours, Vincent; Lupski, James R.; Stratakis, Constantine A.; Beckers., Albert

2016-01-01

Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101. We studied XLAG syndrome patients (N=18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome were identified with Xq26.3 duplications using high definition array comparative genome hybridization (HD-aCGH). We noted males with XLAG had a decreased log2 ratio compared with expected values, suggesting potential mosaicism, while females showed no such decrease. As compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1-53.8%. These characteristics were replicated using a novel, personalized breakpoint-junction specific quantification droplet digital PCR (ddPCR) technique. Using a separate ddPCR technique we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism and identified one female gigantism patient that had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes. PMID:26935837

Detection of mutations in the COL4A5 gene by SSCP in X-linked Alport syndrome

DEFF Research Database (Denmark)

Hertz, Jens Michael; Juncker, I; Persson, U

2001-01-01

, three in-frame deletions, four nonsense mutations, and six splice site mutations. Twenty-two of the mutations have not previously been reported. Furthermore, we found one non-pathogenic amino acid substitution, one rare variant in a non-coding region, and one polymorphism with a heterozygosity of 28...... of type IV-collagen. We performed mutation analysis of the COL4A5 gene by PCR-SSCP analysis of each of the 51 exons with flanking intronic sequences in 81 patients suspected of X-linked Alport syndrome including 29 clear X-linked cases, 37 cases from families with a pedigree compatible with X...

Effects of combined X-radiation and UV-radiation on HeLa cells

International Nuclear Information System (INIS)

Luible, M.

1982-01-01

A combined X-ray-UV irradiation was performed in nonsynchronized HeLa-cells. A pre-irradiation with UV-light, that reduced the survival rate to 42% and the following X-ray radiation yielded a similar dose-effect characteristic as with ordinary X-ray irradiation, only its shoulder was smaller. An additive radiation interaction with the cellular molecular structure was observed. A pre-irradiation with X-rays followed by step-wise UV-irradiation yielded a function similar to the UV-action curve but also with a narrower shoulder. A additive effect could be observed. One can conclude from this that in combined irradiation two interacting processes cause the death of the cells. The gene mutations caused by UV-light lead to cell death. X-rays however cause chromosome breaks, that in an unfavourable combination also lead to cell death. The DNA distorsion caused by the UV-light increases the possibility of misrepair. (orig.) [de

Kinetically directed combination therapy with adriamycin and x-irradiation in a mammary tumor model

International Nuclear Information System (INIS)

Braunschweiger, P.G.; Schenken, L.L.; Schiffer, L.M.

1981-01-01

In the present studies, the interaction of adriamycin (A) and x-irradiation (X) in T1699 mouse mammary tumors was evaluated. Mitotic indices and thymidine labeling indices were determined at various intervals after A or X alone, and after A + X given in combination. The results with A (1.0 mg/kg) and X(200 R) alone suggest that those quantities of each agent induce a G 2 progression delay of 9 to 12 h. The kinetic results after A + X in combination indicated increased S phase transit time and G 2 progression delay. Recovery kinetics after A + X were used to predict optimum sequence intervals for subsequent A + X fractions. Sequential A + X treatment schedules, up to 4 fractions, were designed and evaluated by regrowth delay measurements. The results indicated that the interaction was additive when A and X were given together in combination. Fractionation of A + X to minimize proliferative recovery between fractions resulted in an enhanced antitumor effect

X linked neonatal centronuclear/myotubular myopathy: evidence for linkage to Xq28 DNA marker loci.

Science.gov (United States)

Thomas, N S; Williams, H; Cole, G; Roberts, K; Clarke, A; Liechti-Gallati, S; Braga, S; Gerber, A; Meier, C; Moser, H

1990-05-01

We have studied the inheritance of several polymorphic Xq27/28 DNA marker loci in two three generation families with the X linked neonatal lethal form of centronuclear/myotubular myopathy (XL MTM). We found complete linkage of XLMTM to all four informative Xq28 markers analysed, with GCP/RCP (Z = 3.876, theta = 0.00), with DXS15 (Z = 3.737, theta = 0.00), with DXS52 (Z = 2.709, theta = 0.00), and with F8C (Z = 1.020, theta = 0.00). In the absence of any observable recombination, we are unable to sublocalise the XLMTM locus further within the Xq28 region. This evidence for an Xq28 localisation may allow us to carry out useful genetic counselling within such families.

Molecular characterization of a novel X-linked syndrome involving developmental delay and deafness.

Science.gov (United States)

Hildebrand, Michael S; de Silva, Michelle G; Tan, Tiong Yang; Rose, Elizabeth; Nishimura, Carla; Tolmachova, Tanya; Hulett, Joanne M; White, Susan M; Silver, Jeremy; Bahlo, Melanie; Smith, Richard J H; Dahl, Hans-Henrik M

2007-11-01

X-linked syndromes associated with developmental delay and sensorineural hearing loss (SNHL) have been characterized at the molecular level, including Mohr-Tranebjaerg syndrome and Norrie disease. In this study we report on a novel X-linked recessive, congenital syndrome in a family with developmental delay and SNHL that maps to a locus associated with mental retardation (MR) for which no causative gene has been identified. The X-linked recessive inheritance and congenital nature of the syndrome was confirmed by detailed clinical investigation and the family history. Linkage mapping of the X-chromosome was conducted to ascertain the disease locus and candidate genes were screened by direct sequencing and STRP analysis. The recessive syndrome was mapped to Xp11.3-q21.32 and a deletion was identified in a regulatory region upstream of the POU3F4 gene in affected family members. Since mutations in POU3F4 cause deafness at the DFN3 locus, the deletion is the likely cause of the SNHL in this family. The choroideremia (CHM) gene was also screened and a novel missense change was identified. The alteration changes the serine residue at position 89 in the Rab escort 1 protein (REP-1) to a cysteine (S89C). Prenylation of Rab proteins was investigated in patients and the location of REP-1 expression in the brain determined. However, subsequent analysis revealed that this change in CHM was polymorphic having no effect on REP-1 function. Although the causative gene at the MR locus in this family has not been identified, there are a number of genes involved in syndromic and nonsyndromic forms of MR that are potential candidates. Copyright 2007 Wiley-Liss, Inc.

X-linked hypophosphatemic rickets and sagittal craniosynostosis: three patients requiring operative cranial expansion: case series and literature review.

Science.gov (United States)

Jaszczuk, Phillip; Rogers, Gary F; Guzman, Raphael; Proctor, Mark R

2016-05-01

A defect in a phosphate-regulating gene leads to the most common form of rickets: X-linked hypophosphatemic rickets (XLH) or vitamin D-resistant rickets (VDDR). XLH has been associated with craniosynostosis, the sagittal suture being the most commonly involved. We present three patients with rickets and symptomatic sagittal suture craniosynostosis all of whom presented late (>2 years of age). Two had a severe phenotype and papilledema, while the third presented with an osseous bulging near the anterior fontanel and experienced chronic headaches. All underwent successful cranial vault expansion. Rachitic patients with scaphocephaly should be screened for craniosynostosis.

Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with "Lorenzo's oil"

NARCIS (Netherlands)

van Geel, B. M.; Assies, J.; Haverkort, E. B.; Koelman, J. H.; Verbeeten, B.; Wanders, R. J.; Barth, P. G.

1999-01-01

OBJECTIVES: X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal fatty acid oxidation, biochemically characterised by the accumulation of saturated very long chain fatty acids (VLCFAs), particularly hexacosanoic acid (C26:0). Dietary treatment with a 4:1 mixture of

Combined X-ray CT and mass spectrometry for biomedical imaging applications

Science.gov (United States)

Schioppa, E., Jr.; Ellis, S.; Bruinen, A. L.; Visser, J.; Heeren, R. M. A.; Uher, J.; Koffeman, E.

2014-04-01

Imaging technologies play a key role in many branches of science, especially in biology and medicine. They provide an invaluable insight into both internal structure and processes within a broad range of samples. There are many techniques that allow one to obtain images of an object. Different techniques are based on the analysis of a particular sample property by means of a dedicated imaging system, and as such, each imaging modality provides the researcher with different information. The use of multimodal imaging (imaging with several different techniques) can provide additional and complementary information that is not possible when employing a single imaging technique alone. In this study, we present for the first time a multi-modal imaging technique where X-ray computerized tomography (CT) is combined with mass spectrometry imaging (MSI). While X-ray CT provides 3-dimensional information regarding the internal structure of the sample based on X-ray absorption coefficients, MSI of thin sections acquired from the same sample allows the spatial distribution of many elements/molecules, each distinguished by its unique mass-to-charge ratio (m/z), to be determined within a single measurement and with a spatial resolution as low as 1 μm or even less. The aim of the work is to demonstrate how molecular information from MSI can be spatially correlated with 3D structural information acquired from X-ray CT. In these experiments, frozen samples are imaged in an X-ray CT setup using Medipix based detectors equipped with a CO2 cooled sample holder. Single projections are pre-processed before tomographic reconstruction using a signal-to-thickness calibration. In the second step, the object is sliced into thin sections (circa 20 μm) that are then imaged using both matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and secondary ion (SIMS) mass spectrometry, where the spatial distribution of specific molecules within the sample is determined. The

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3)

International Nuclear Information System (INIS)

Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-01-01

Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF 1 mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free. (author)

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.

Science.gov (United States)

Schneider, Holm; Faschingbauer, Florian; Schuepbach-Mallepell, Sonia; Körber, Iris; Wohlfart, Sigrun; Dick, Angela; Wahlbuhl, Mandy; Kowalczyk-Quintas, Christine; Vigolo, Michele; Kirby, Neil; Tannert, Corinna; Rompel, Oliver; Rascher, Wolfgang; Beckmann, Matthias W; Schneider, Pascal

2018-04-26

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.).

Recurrent Anion Gap Acidosis: An Unusual Presentation of X-Linked Adrenoleukodystrophy in a Five-year-old Male.

Science.gov (United States)

Schwab, Joel; Pena, Loren; Sigman, Laura; Waggoner, Darrel

2010-01-01

We are presenting a five-year-old male with recurrent anion gap acidosis. During his last admission, it was detected that he had elevated VLCFA and the evaluation discovered that he had X-linked Adrenooleukodystrophy. He had the Addisonian only phenotype without any clinical or radiographic CNS findings. We were unable to find any other reports of this presentation of ALD. If the work-up of recurrent anion gap acidosis does not uncover an etiology, X-linked ALD should be considered in the differential diagnosis.

Mechanical design of ultraprecision weak-link stages for nanometer-scale x-ray imaging

Energy Technology Data Exchange (ETDEWEB)

Shu, D [APS Engineering Support Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Maser, J, E-mail: shu@aps.anl.go [Center for Nanoscale Materials, Argonne National Laboratory, Argonne, IL 60439 (United States)

2009-09-01

A nanopositioning diagnostic setup has been built to support the Argonne Center for Nanoscale Materials (CNM) nanoprobe instrument commissioning process at the APS. Its laser Doppler interferometer system provides subnanometer positioning diagnostic resolution with large dynamic range. A set of original APS designed ultraprecision PZT-driven weak-link stages with high-stiffness motor-driven stages has been tested with this diagnostic setup. In this paper we present a preliminary test result of the ultraprecision weak-link stage system developed for the CNM hard x-ray nanoprobe instrument at APS sector 26. A test result for a novel laminar weak-link mechanism with sub-centimeter travel range and sub-nanometer positioning resolution is also introduced in this paper as a future work.

Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation.

NARCIS (Netherlands)

Kalscheuer, V.M.M.; Freude, K.; Musante, L.; Jensen, L.R.; Yntema, H.G.; Gecz, J.; Sefiani, A.; Hoffmann, K.; Moser, B.; Haas, S.; Gurok, U.; Haesler, S.; Aranda, B.; Nshedjan, A.; Tzschach, A.; Hartmann, N.; Roloff, T.C.; Shoichet, S.; Hagens, O.; Tao, J.; Bokhoven, J.H.L.M. van; Turner, G.; Chelly, J.; Moraine, C.; Fryns, J.P.; Nuber, U.; Hoeltzenbein, M.; Scharff, C.; Scherthan, H.; Lenzner, S.; Hamel, B.C.J.; Schweiger, S.; Ropers, H.H.

2003-01-01

We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously

Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation

DEFF Research Database (Denmark)

Kalscheuer, Vera M; Freude, Kristine; Musante, Luciana

2003-01-01

We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previou...

Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation

NARCIS (Netherlands)

Kalscheuer, VM; Freude, K; Musante, L; Jensen, LR; Yntema, HG; Gecz, J; Sefiani, A; Hoffmann, K; Moser, B; Haas, S; Gurok, U; Haesler, S; Aranda, B; Nshedjan, A; Tzschach, A; Hartmann, N; Roloff, TC; Shoichet, S; Hagens, O; Tao, J; van Bokhoven, H; Turner, G; Chelly, J; Moraine, C; Fryns, JP; Nuber, U; Hoeltzenbein, M; Scharff, C; Scherthan, H; Lenzner, S; Hamel, BCJ; Schweiger, S; Ropers, Hans-Hilger

2003-01-01

We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously

Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

Science.gov (United States)

Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

2014-08-01

Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease

NARCIS (Netherlands)

Sillevis Smitt, J. H.; Weening, R. S.; Krieg, S. R.; Bos, J. D.

1990-01-01

A questionnaire was sent to 16 carriers of the X-linked cytochrome-b558 negative variant of chronic granulomatous disease (CGD). Of the 15 who answered the questionnaire and from data of one additional case, 70% reported recurrent aphthous stomatitis and 63% had recurrent skin eruptions. Five of the

X-Linked Lymphoproliferative Disease Presenting as Pancytopenia in a 10-Month-Old Boy

Directory of Open Access Journals (Sweden)

S. Nicole Chadha

2010-01-01

Full Text Available X-linked lymphoproliferative disease, also known as Duncan's syndrome, is a rare genetic disorder that causes exaggerated immune responses to Epstein-Barr virus (EBV infection and often leads to death. Patient presentation varies but can include signs and symptoms typical of EBV, pancytopenia, and fulminant hepatitis.

Three Ways to Link Merge with Hierarchical Concept-Combination

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Chris Thornton

2016-11-01

Full Text Available In the Minimalist Program, language competence is seen to stem from a fundamental ability to construct hierarchical structure, an operation dubbed ‘Merge’. This raises the problem of how to view hierarchical concept-combination. This is a conceptual operation which also builds hierarchical structure. We can conceive of a garden that consists of a lawn and a flower-bed, for example, or a salad consisting of lettuce, fennel and rocket, or a crew consisting of a pilot and engineer. In such cases, concepts are put together in a way that makes one the accommodating element with respect to the others taken in combination. The accommodating element becomes the root of a hierarchical unit. Since this unit is itself a concept, the operation is inherently recursive. Does this mean the mind has two independent systems of hierarchical construction? Or is some form of integration more likely? Following a detailed examination of the operations involved, this paper shows there are three main ways in which Merge might be linked to hierarchical concept-combination. Also examined are the architectural implications that arise in each case.

X-ray analysis of 80 patients with severe endemic fluorosis caused by coal burning

Energy Technology Data Exchange (ETDEWEB)

Zhao, Z.P.; Yuan, M.B.; Liu, G.F. [Luzhou Medical College, Luzhou (China)

1996-05-01

Radiographs of 80 patients with severe endemic fluorosis of coalburning type (CBFF) - 49 males and 31 females aged 30 to 70 years - were analysed to examine the changes to the bone substance, peripheral structure of bone, and joints. The changes to bone substance were: (1) osteosclerosis type, 62 cases (77.5%); (2) mixed type, 16 cases (21.25%); (3) osteoporosis type, one case (1.25%); (4) osteomalacia type, one case (1.25%). The changes to the joints were found in the hips and elbows in 79 cases (98.75%), and in the knees in 75 cases (93.75%). When combinations of the above three changes occur, the classification of the disease is according to the most severe one of the three. Our findings can increase the accuracy of X-ray diagnosis, making it more consistent with clinical diagnosis, thus improving prevention and treatment of CBEF.

Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder

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Kumiko Yanagi

2012-01-01

Full Text Available Mutations in the X-linked genes neuroligin 3 (NLGN3 and neuroligin 4X (NLGN4X were first implicated in the pathogenesis of X-linked autism in Swedish families. However, reports of mutations in these genes in autism spectrum disorder (ASD patients from various ethnic backgrounds present conflicting results regarding the etiology of ASD, possibly because of genetic heterogeneity and/or differences in their ethnic background. Additional mutation screening study on another ethnic background could help to clarify the relevance of the genes to ASD. We scanned the entire coding regions of NLGN3 and NLGN4X in 62 Japanese patients with ASD by polymerase chain reaction-high-resolution melting curve and direct sequencing analyses. Four synonymous substitutions, one in NLGN3 and three in NLGN4X, were identified in four of the 62 patients. These substitutions were not present in 278 control X-chromosomes from unrelated Japanese individuals and were not registered in the database of Single Nucleotide Polymorphisms build 132 or in the Japanese Single Nucleotide Polymorphisms database, indicating that they were novel and specific to ASD. Though further analysis is necessary to determine the physiological and clinical importance of such substitutions, the possibility of the relevance of both synonymous and nonsynonymous substitutions with the etiology of ASD should be considered.

Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

OpenAIRE

Naves, Luciana A.; Daly, Adrian Francis; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Junior, Armindo Jreige; Neto, Florencio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S.; Stratakis, Constantine A.; Lupski, James R.

2016-01-01

X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm,...

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

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Dussaillant Catalina

2012-11-01

Full Text Available Abstract Background Severe hypertriglyceridemia (HTG has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. Methods We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel. Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. Results A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. Conclusion The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

APOA5 Q97X mutation identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family.

Science.gov (United States)

Dussaillant, Catalina; Serrano, Valentina; Maiz, Alberto; Eyheramendy, Susana; Cataldo, Luis Rodrigo; Chavez, Matías; Smalley, Susan V; Fuentes, Marcela; Rigotti, Attilio; Rubio, Lorena; Lagos, Carlos F; Martinez, José Alfredo; Santos, José Luis

2012-11-15

Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB

NARCIS (Netherlands)

Wolach, Baruch; Scharf, Yitshak; Gavrieli, Ronit; de Boer, Martin; Roos, Dirk

2005-01-01

Most patients with chronic granulomatous disease (CGD) have mutations in the X-linked CYBB gene that encodes gp91(phox), a component of the phagocyte NADPH oxidase. The resulting X-linked form of CGD is usually manifested in boys. Rarely, X-CGD is encountered in female carriers with extreme

Diffuse X-Ray Scattering from Several Platinum Chain Compounds

DEFF Research Database (Denmark)

Braude, A.; Lindegaard-Andersen, Asger; Carneiro, K.

1980-01-01

Values of the Fermi wavevector for several platinum based one-dimensional conductors were determined from diffuse X-ray scattering measurements. The values were compared with those expected from the chemical compositions. The importance of conclusive values of this parameter is stressed and the c...

Genotype-phenotype correlation in boys with X-linked hypohidrotic ectodermal dysplasia.

Science.gov (United States)

Burger, Kristin; Schneider, Anne-Theres; Wohlfart, Sigrun; Kiesewetter, Franklin; Huttner, Kenneth; Johnson, Ramsey; Schneider, Holm

2014-10-01

X-linked hypohidrotic ectodermal dysplasia (XLHED), the most frequent form of ectodermal dysplasia, is a genetic disorder of ectoderm development characterized by malformation of multiple ectodermal structures such as skin, hair, sweat and sebaceous glands, and teeth. The disease is caused by a broad spectrum of mutations in the gene EDA. Although XLHED symptoms show inter-familial and intra-familial variability, genotype-phenotype correlation has been demonstrated with respect to sweat gland function. In this study, we investigated to which extent the EDA genotype correlates with the severity of XLHED-related skin and hair signs. Nineteen male children with XLHED (age range 3-14 years) and seven controls (aged 6-14 years) were examined by confocal microscopy of the skin, quantification of pilocarpine-induced sweating, semi-quantitative evaluation of full facial photographs with respect to XLHED-related skin issues, and phototrichogram analysis. All eight boys with known hypomorphic EDA mutations were able to produce at least some sweat and showed less severe cutaneous signs of XLHED than the anhidrotic XLHED patients (e.g., perioral and periorbital eczema or hyperpigmentation, regional hyperkeratosis, characteristic wrinkles under the eyes). As expected, individuals with XLHED had significantly less and thinner hair than healthy controls. However, there were also significant differences in hair number, diameter, and other hair characteristics between the group with hypomorphic EDA mutations and the anhidrotic patients. In summary, this study indicated a remarkable genotype-phenotype correlation of skin and hair findings in prepubescent males with XLHED. © 2014 Wiley Periodicals, Inc.

Epstein-Barr virus induced hemophagocytic lymphohistiocytosis in X-linked lymphoproliferative disease

Directory of Open Access Journals (Sweden)

Senthilkumar Sankararaman

2014-01-01

Full Text Available X-linked lymphoproliferative disease (XLP is a rare, often fatal genetic disorder characterized by extreme vulnerability to Epstein-Barr virus (EBV. EBV-induced hemophagocytic lymphohistiocytosis (HLH is a known presentation in XLP. In EBV-induced HLH in XLP, the brain imaging findings in the acute phase include a non specific pattern. In this report, we highlight the magnetic resonance imaging and magnetic resonance spectroscopy findings in a child with EBV induced HLH in XLP.

Papilledema in the Setting of X-Linked Hypophosphatemic Rickets with Craniosynostosis

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Lora R. Dagi Glass

2011-12-01

Full Text Available Purpose: Introduction to the ophthalmic literature of an unusual cause of papilledema and subsequent optic atrophy: X-linked hypophosphatemic rickets (XLH. Methods: Case report of a 3-year-old female presenting with papilledema resulting from craniosynostosis secondary to XLH. Results: Early intervention with craniofacial surgery prevented the development of optic atrophy. Conclusion: Children with XLH should be screened for ophthalmic evidence of elevated intracranial pressure to aid early intervention and prevention of permanent loss of vision.

The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies

NARCIS (Netherlands)

D'Adamo, P.; Fassone, L.; Gedeon, A.; Janssen, E. A.; Bione, S.; Bolhuis, P. A.; Barth, P. G.; Wilson, M.; Haan, E.; Orstavik, K. H.; Patton, M. A.; Green, A. J.; Zammarchi, E.; Donati, M. A.; Toniolo, D.

1997-01-01

Barth syndrome (BTHS) is an X-linked disorder characterized clinically by the associated features of cardiac and skeletal myopathy, short stature, and neutropenia. The clinical manifestations of the disease are, in general, quite variable, but cardiac failure as a consequence of cardiac dilatation

Dilemmas in counselling females with the fragile X syndrome

NARCIS (Netherlands)

B.B.A. de Vries (Bert); H.M. van den Boer-van den Berg; M.F. Niermeijer (Martinus); A. Tibben (Arend)

1999-01-01

textabstractThe dilemmas in counselling a mildly retarded female with the fragile X syndrome and her retarded partner are presented. The fragile X syndrome is an X linked mental retardation disorder that affects males and, often less severely, females. Affected females

A combined scanning tunnelling microscope and x-ray interferometer

Science.gov (United States)

Yacoot, Andrew; Kuetgens, Ulrich; Koenders, Ludger; Weimann, Thomas

2001-10-01

A monolithic x-ray interferometer made from silicon and a scanning tunnelling microscope have been combined and used to calibrate grating structures with periodicities of 100 nm or less. The x-ray interferometer is used as a translation stage which moves in discrete steps of 0.192 nm, the lattice spacing of the silicon (220) planes. Hence, movements are traceable to the definition of the metre and the nonlinearity associated with the optical interferometers used to measure displacement in more conventional metrological scanning probe microscopes (MSPMs) removed.

Methylation state of the EDA gene promoter in Chinese X-linked hypohidrotic ectodermal dysplasia carriers.

Directory of Open Access Journals (Sweden)

Wei Yin

Full Text Available Hypodontia, hypohidrosis, sparse hair and characteristic faces are the main characters of X-linked hypohidrotic ectodermal dysplasia (XLHED which is caused by genetic ectodysplasin A (EDA deficiency. Heterozygous female carriers tend to have mild to moderate XLHED phenotype, even though 30% of them present no obvious symptom.A large Chinese XLHED family was reported and the entire coding region and exon-intron boundaries of EDA gene were sequenced. To elucidate the mechanism for carriers' tempered phenotype, we analyzed the methylation level on four sites of the promoter of EDA by the pyrosequencing system.A known frameshift mutation (c.573-574 insT was found in this pedigree. Combined with the pedigrees we reported before, 120 samples comprised of 23 carrier females from 11 families and 97 healthy females were analyzed for the methylation state of EDA promoter. Within 95% confidence interval (CI, 18 (78.26% carriers were hypermethylated at these 4 sites.Chinese XLHED carriers often have a hypermethylated EDA promoter.

Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and other primary immunodeficiency diseases

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O. Jilkina

2014-01-01

Full Text Available In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency (SCID is three-fold higher than the national average, with SCID overrepresented in two population groups: Mennonites and First Nations of Northern Cree ancestries. T-cell receptor excision circle (TREC assay is being used increasingly for neonatal screening for SCID in North America. However, the majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely that the TREC assay will not identify these infants. The goal of this study was to blindly and retrospectively perform TREC analysis in confirmed SCID patients using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative SCID (3 with adenosine deaminase deficiency, 1 with CD3δ deficiency, and 1 unclassified and 8 T-positive SCID (5 with zeta chain-associated protein kinase (ZAP70 deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ deficiency. As a non-SCID patient group, 5 Primary Immunodeficiency Disease (PID patients were studied: 1 T-negative PID (cartilage-hair hypoplasia and 4 T-positive PID (2 common immune deficiency (CID, 1 Wiskott–Aldrich syndrome, and 1 X-linked lymphoproliferative disease. Both patient groups required hematopoietic stem cell transplantation. In addition, randomly-selected de-identified controls (n = 982 were tested. Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in 2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified controls. Conclusions: TREC method will identify T-negative SCID and T-negative PID. To identify other SCID babies, newborn screening in Manitoba must include supplemental targeted screening for ethnic-specific mutations.

Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia.

Science.gov (United States)

Goodwin, Alice F; Larson, Jacinda R; Jones, Kyle B; Liberton, Denise K; Landan, Maya; Wang, Zhifeng; Boekelheide, Anne; Langham, Margaret; Mushegyan, Vagan; Oberoi, Snehlata; Brao, Rosalie; Wen, Timothy; Johnson, Ramsey; Huttner, Kenneth; Grange, Dorothy K; Spritz, Richard A; Hallgrímsson, Benedikt; Jheon, Andrew H; Klein, Ophir D

2014-09-01

Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.

The combined effects of MRI and x-rays on ICR mouse embryos during organogenesis

International Nuclear Information System (INIS)

Gu, Yeunhwa; Hasegawa, Takeo; Yamamoto, Youichi; Kai, Michiaki; Kusama, Tomoko

2001-01-01

The combined effects of X-rays and magnetic resonance imaging (MRI) on mouse embryos at an early stage of organogenesis were investigated. Pregnant ICR mice were irradiated on day 8 of gestation with X-rays at a dose of 1 Gy and/or MRI at 0.5 T for 1 hour. The mortality rates of the embryos or fetuses, the incidence of external malformations, the fetal body weight and the sex ratio were observed at day 18 of gestation. A significant increase in embryonic mortality was observed after exposure to either 1 Gy of X-radiation or 0.5 T MRI. However, the combined X-rays and MRI did not show a statistically significant increase in embryonic mortality compared with the control. External malformations, such as exencephaly, a cleft palate and anophthalmia, were observed in mice irradiated with X-rays and/or MRI. The incidence of each malformation in all treated groups increased with statistical significance compared with the control mice. The incidence in mice irradiated with both X-rays and MRI was lower than in mice irradiated with only X-rays. The combined effects of the combination of radiation and MRI on the external malformations might be antagonistic. There were no statistically significant differences in fetal death, fetal body weight and sex ratio among all experimental groups. (author)

The combined effects of MRI and x-rays on ICR mouse embryos during organogenesis

Energy Technology Data Exchange (ETDEWEB)

Gu, Yeunhwa; Hasegawa, Takeo; Yamamoto, Youichi [Suzuka Univ. of Medical Science, Mie (Japan); Kai, Michiaki; Kusama, Tomoko

2001-09-01

The combined effects of X-rays and magnetic resonance imaging (MRI) on mouse embryos at an early stage of organogenesis were investigated. Pregnant ICR mice were irradiated on day 8 of gestation with X-rays at a dose of 1 Gy and/or MRI at 0.5 T for 1 hour. The mortality rates of the embryos or fetuses, the incidence of external malformations, the fetal body weight and the sex ratio were observed at day 18 of gestation. A significant increase in embryonic mortality was observed after exposure to either 1 Gy of X-radiation or 0.5 T MRI. However, the combined X-rays and MRI did not show a statistically significant increase in embryonic mortality compared with the control. External malformations, such as exencephaly, a cleft palate and anophthalmia, were observed in mice irradiated with X-rays and/or MRI. The incidence of each malformation in all treated groups increased with statistical significance compared with the control mice. The incidence in mice irradiated with both X-rays and MRI was lower than in mice irradiated with only X-rays. The combined effects of the combination of radiation and MRI on the external malformations might be antagonistic. There were no statistically significant differences in fetal death, fetal body weight and sex ratio among all experimental groups. (author)

A recoding scheme for X-linked and pseudoautosomal loci to be used with computer programs for autosomal LOD-score analysis.

Science.gov (United States)

Strauch, Konstantin; Baur, Max P; Wienker, Thomas F

2004-01-01

We present a recoding scheme that allows for a parametric multipoint X-chromosomal linkage analysis of dichotomous traits in the context of a computer program for autosomes that can use trait models with imprinting. Furthermore, with this scheme, it is possible to perform a joint multipoint analysis of X-linked and pseudoautosomal loci. It is required that (1) the marker genotypes of all female nonfounders are available and that (2) there are no male nonfounders who have daughters in the pedigree. The second requirement does not apply if the trait locus is pseudoautosomal. The X-linked marker loci are recorded by adding a dummy allele to the males' hemizygous genotypes. For modelling an X-linked trait locus, five different liability classes are defined, in conjunction with a paternal imprinting model for male nonfounders. The formulation aims at the mapping of a diallelic trait locus relative to an arbitrary number of codominant markers with known genetic distances, in cases where a program for a genuine X-chromosomal analysis is not available. 2004 S. Karger AG, Basel.

Inherent X-Linked Genetic Variability and Cellular Mosaicism Unique to Females Contribute to Sex-Related Differences in the Innate Immune Response

Directory of Open Access Journals (Sweden)

Zoltan Spolarics

2017-11-01

Full Text Available Females have a longer lifespan and better general health than males. Considerable number of studies also demonstrated that, after trauma and sepsis, females present better outcomes as compared to males indicating sex-related differences in the innate immune response. The current notion is that differences in the immuno-modulatory effects of sex hormones are the underlying causative mechanism. However, the field remains controversial and the exclusive role of sex hormones has been challenged. Here, we propose that polymorphic X-linked immune competent genes, which are abundant in the population are important players in sex-based immuno-modulation and play a key role in causing sex-related outcome differences following trauma or sepsis. We describe the differences in X chromosome (ChrX regulation between males and females and its consequences in the context of common X-linked polymorphisms at the individual as well as population level. We also discuss the potential pathophysiological and immune-modulatory aspects of ChrX cellular mosaicism, which is unique to females and how this may contribute to sex-biased immune-modulation. The potential confounding effects of ChrX skewing of cell progenitors at the bone marrow is also presented together with aspects of acute trauma-induced de novo ChrX skewing at the periphery. In support of the hypothesis, novel observations indicating ChrX skewing in a female trauma cohort as well as case studies depicting the temporal relationship between trauma-induced cellular skewing and the clinical course are also described. Finally, we list and discuss a selected set of polymorphic X-linked genes, which are frequent in the population and have key regulatory or metabolic functions in the innate immune response and, therefore, are primary candidates for mediating sex-biased immune responses. We conclude that sex-related differences in a variety of disease processes including the innate inflammatory response to injury

Inference of the phase-to-mechanical property link via coupled X-ray spectrometry and indentation analysis: Application to cement-based materials

Energy Technology Data Exchange (ETDEWEB)

Krakowiak, Konrad J.; Wilson, William [Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139-4307 (United States); James, Simon [Schlumberger Riboud Product Center, 1 Rue Henri Becquerel, Clamart 92140 (France); Musso, Simone [Schlumberger-Doll Research Center, 1 Hampshire St., Cambridge, MA 02139-1578 (United States); Ulm, Franz-Josef, E-mail: ulm@mit.edu [Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139-4307 (United States)

2015-01-15

A novel approach for the chemo-mechanical characterization of cement-based materials is presented, which combines the classical grid indentation technique with elemental mapping by scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDS). It is illustrated through application to an oil-well cement system with siliceous filler. The characteristic X-rays of major elements (silicon, calcium and aluminum) are measured over the indentation region and mapped back on the indentation points. Measured intensities together with indentation hardness and modulus are considered in a clustering analysis within the framework of Finite Mixture Models with Gaussian component density function. The method is able to successfully isolate the calcium-silica-hydrate gel at the indentation scale from its mixtures with other products of cement hydration and anhydrous phases; thus providing a convenient means to link mechanical response to the calcium-to-silicon ratio quantified independently via X-ray wavelength dispersive spectroscopy. A discussion of uncertainty quantification of the estimated chemo-mechanical properties and phase volume fractions, as well as the effect of chemical observables on phase assessment is also included.

Relapsing Campylobacter jejuni Systemic Infections in a Child with X-Linked Agammaglobulinemia

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Paola Ariganello

2013-01-01

Full Text Available X-linked agammaglobulinemia (XLA is a primary immunodeficiency of the humoral compartment, due to a mutation in the Bruton tyrosine kinase (BTK gene, characterized by a severe defect of circulating B cells and serum immunoglobulins. Recurrent infections are the main clinical manifestations; although they are especially due to encapsulated bacteria, a specific association with Campylobacter species has been reported. Here, we report the case of a boy with XLA who presented with relapsing Campylobacter jejuni systemic infections. His clinical history supports the hypothesis of the persistence of C. jejuni in his intestinal tract. Indeed, as previously reported, XLA patients may become chronic intestinal carriers of Campylobacter, even in absence of symptoms, with an increased risk of relapsing bacteraemia. The humoral defect is considered to be crucial for this phenomenon, as well as the difficulties to eradicate the pathogen with an appropriate antibiotic therapy; drug resistance is raising in Campylobacter species, and the appropriate duration of treatment has not been established. C. jejuni should always be suspected in XLA patients with signs and symptoms of systemic infection, and treatment should be based on antibiogram to assure the eradication of the pathogen.

Isolation and characterization of X-linked mutants of Drosophila melanogaster which are sensitive to mutagens

International Nuclear Information System (INIS)

Boyd, J.B.; Golino, M.D.; Nguyen, T.D.; Green, M.M.

1976-01-01

Thirteen X-linked mutants have been isolated in Drosophila melanogaster which render male and homozygous female larvae sensitive to the mutagen methyl methanesulfonate. Their characterization and preliminary assignment to functional groups is described. Four of these mutants are alleles of mei-41. Like previously isolated alleles of this locus, these mutants reduce fertility and increase loss and nondisjunction of the X-chromosome in homozygous females. The remaining mutants have been tentatively assigned to six functional groups (two mutants to the mus(1)101 locus, two to mus(1)102, two to mus(1)103, and one each to mus(1)104, mus(1)105, and mus(1)106. Several of the complementation groups can be distinguished on the basis of nondisjunction and cross sensitivity to mutagens. Females homozygous for the mei-41, mus(1)101 and mus(1)102 mutants exhibit elevated levels of nondisjunction. Mutants belonging to complementation groups mei-41, mus(1)101, and mus(1)104 are sensitive to nitrogen mustard (HN2) in addition to their MMS sensitivity. Among these mutants there is currently a direct correlation between sensitivity to HN2, sensitivity to 2-acetylaminofluorene and a deficiency in post-replication repair. Only the mei-41 mutants are hypersensitive to uv radiation, although several of the mutants exhibit sensitivity to γ-rays. Semidominance is observed in female larvae of the mei-41, mus(1)104, and mus(1)103 mutants after exposure to high concentrations of MMS. The properties of the mutants generally conform to a pattern which has been established for related mutants in yeast

Multipoint linkage analysis in X-linked ocular albinism of the Nettleship-Falls type

NARCIS (Netherlands)

Bergen, A. A.; Samanns, C.; Schuurman, E. J.; van Osch, L.; van Dorp, D. B.; Pinckers, A. J.; Bakker, E.; Gal, A.; van Ommen, G. J.; Bleeker-Wagemakers, E. M.

1991-01-01

An extensive linkage analysis was performed by studying ten Xp22 loci in ten families segregating for X-linked ocular albinism of the Nettleship-Falls type (XOA). Linkage was confirmed between the XOA locus (OA1) and both DXS16 (theta max = 0.10, zeta max = 4.09) and DXS237 (theta max = 0.12, zeta

Phenotypic heterogeneity and mutational spectrum in a cohort of 45 Italian males subjects with X-linked ectodermal dysplasia.

Science.gov (United States)

Guazzarotti, L; Tadini, G; Mancini, G E; Giglio, S; Willoughby, C E; Callea, M; Sani, I; Nannini, P; Mameli, C; Tenconi, A A; Mauri, S; Bottero, A; Caimi, A; Morelli, M; Zuccotti, G V

2015-04-01

Ectodermal dysplasias (EDs) are a group of genetic disorders characterized by the abnormal development of the ectodermal-derived structures. X-linked hypohidrotic ectodermal dysplasia, resulting from mutations in ED1 gene, is the most common form. The main purpose of this study was to characterize the phenotype spectrum in 45 males harboring ED1 mutations. The study showed that in addition to the involvement of the major ectodermal tissues, the majority of patients also have alterations of several minor ectodermal-derived structures. Characterizing the clinical spectrum resulting from ED1 gene mutations improves diagnosis and can direct clinical care. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Autosomal-recessive and X-linked forms of hereditary motor and sensory neuropathy in childhood.

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Ouvrier, Robert; Geevasingha, Nimeshan; Ryan, Monique M

2007-08-01

The hereditary motor and sensory neuropathies (HMSNs, Charcot-Marie-Tooth neuropathies) are the most common degenerative disorders of the peripheral nervous system. In recent years a dramatic expansion has occurred in our understanding of the molecular basis and cell biology of the recessively inherited demyelinating and axonal neuropathies, with delineation of a number of new neuropathies. Mutations in some genes cause a wide variety of clinical, neurophysiologic, and pathologic phenotypes, rendering diagnosis difficult. The X-linked forms of HMSN represent at least 10%-15% of all HMSNs and have an expanded disease spectrum including demyelinating, intermediate, and axonal neuropathies, transient central nervous system (CNS) dysfunction, mental retardation, and hearing loss. This review presents an overview of the recessive and X-linked forms of HMSN observed in childhood, with particular reference to disease phenotype and neurophysiologic and pathologic abnormalities suggestive of specific diagnoses. These findings can be used by the clinician to formulate a differential diagnosis and guide targeted genetic testing.

Effect of X-rays combined with ACNU and O sup 6 -ethylguanine on rat subcutaneous gliomas

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Takahashi, Kou; Katakura, Rhuichi; Mashiyama, Shoji; Yoshimoto, Takashi; Suzuki, Jiro (Tohoku Univ., Sendai (Japan). School of Medicine); Sasaki, Takehito

1991-06-01

Rat gliomas of subcutaneously transplanted RGc-6 cells were irradiated with X-ray either alone, or combined with ACNU, and the cell-survival was assayed in vitro. Cell-survival curve composed of two components by X-irradiation alone indicated the presence of a hypoxic cell fraction. We have previously shown that combined treatment with ACNU apparently made the effect of X-ray on spheroids in vitro of the same cell line of RGc-6 more powerful. Although treatment of rat gliomas with ACNU administered at 2 hrs prior to X-irradiation was most effective, it resulted in only the additive effect of the independent action of the two agents. Further treatment by O{sup 6}-ethylguanine prior to ACNU administration and X-irradiation apparently increased the strength of the effect of ACNU combined with X-ray to the dose-modifying factor for X-ray of 1.8. The result indicated that the combination of O{sup 6}-ethylguanine prior to ACNU administration and X-irradiation may clinically enhance the effect of X-ray against apparent ACNU-resistant glioma cells such as RGc-6 cells. (author).

Development of a combined portable x-ray fluorescence and Raman spectrometer for in situ analysis.

Science.gov (United States)

Guerra, M; Longelin, S; Pessanha, S; Manso, M; Carvalho, M L

2014-06-01

In this work, we have built a portable X-ray fluorescence (XRF) spectrometer in a planar configuration coupled to a Raman head and a digital optical microscope, for in situ analysis. Several geometries for the XRF apparatus and digital microscope are possible in order to overcome spatial constraints and provide better measurement conditions. With this combined spectrometer, we are now able to perform XRF and Raman measurements in the same point without the need for sample collection, which can be crucial when dealing with cultural heritage objects, as well as forensic analysis. We show the capabilities of the spectrometer by measuring several standard reference materials, as well as other samples usually encountered in cultural heritage, geological, as well as biomedical studies.

Skewed X-inactivation in cloned mice

International Nuclear Information System (INIS)

Senda, Sho; Wakayama, Teruhiko; Yamazaki, Yukiko; Ohgane, Jun; Hattori, Naka; Tanaka, Satoshi; Yanagimachi, Ryuzo; Shiota, Kunio

2004-01-01

In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P < 0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders

A previously unidentified deletion in G protein-coupled receptor 143 causing X-linked congenital nystagmus in a Chinese family

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Jing Liu

2016-01-01

Full Text Available Background: Congenital nystagmus (CN is characterized by conjugated, spontaneous, and involuntary ocular oscillations. It is an inherited disease and the most common inheritance pattern is X-linked CN. In this study, our aim is to identify the disease-causing mutation in a large sixth-generation Chinese family with X-linked CN. Methods: It has been reported that mutations in four-point-one, ezrin, radixin, moesin domain-containing 7 gene (FRMD7 and G protein-coupled receptor 143 gene (GPR143 account for the majority patients of X-linked nystagmus. We collected 8 ml blood samples from members of a large sixth-generation pedigree with X-linked CN and 100 normal controls. FRMD7 and GPR143 were scanned by polymerase chain reaction (PCR-based DNA sequencing assays, and multiplex PCR assays were applied to detect deletions. Results: We identified a previously unreported deletion covering 7 exons in GPR143 in a Chinese family. The heterozygous deletion from exon 3 to exon 9 of GPR143 was detected in all affected males in the family, while it was not detected in other unaffected relatives or 100 normal controls. Conclusions: This is the first report of molecular characterization in GPR143 gene in the CN family. Our results expand the spectrum of GPR143 mutations causing CN and further confirm the role of GPR143 in the pathogenesis of CN.

An X-linked Myh11-CreERT2 mouse line resulting from Y to X chromosome-translocation of the Cre allele.

Science.gov (United States)

Liao, Mingmei; Zhou, Junmei; Wang, Fen; Ali, Yasmin H; Chan, Kelvin L; Zou, Fei; Offermanns, Stefan; Jiang, Zhisheng; Jiang, Zhihua

2017-09-01

The Myh11-CreER T2 mouse line (Cre + ) has gained increasing application because of its high lineage specificity relative to other Cre drivers targeting smooth muscle cells (SMCs). This Cre allele, however, was initially inserted into the Y chromosome (X/Y Cre+ ), which excluded its application in female mice. Our group established a Cre + colony from male ancestors. Surprisingly, genotype screening identified female carriers that stably transmitted the Cre allele to the following generations. Crossbreeding experiments revealed a pattern of X-linked inheritance for the transgene (k > 1000), indicating that these female carries acquired the Cre allele through a mechanism of Y to X chromosome translocation. Further characterization demonstrated that in hemizygous X/X Cre+ mice Cre activity was restricted to a subset arterial SMCs, with Cre expression in arteries decreased by 50% compared to X/Y Cre+ mice. This mosaicism, however, diminished in homozygous X Cre+ /X Cre+ mice. In a model of aortic aneurysm induced by a SMC-specific Tgfbr1 deletion, the homozygous X Cre+ /X Cre+ Cre driver unmasked the aortic phenotype that is otherwise subclinical when driven by the hemizygous X/X Cre+ Cre line. In conclusion, the Cre allele carried by this female mouse line is located on the X chromosome and subjected to X-inactivation. The homozygous X Cre+ /X Cre+ mice produce uniform Cre activity in arterial SMCs. © 2017 Wiley Periodicals, Inc.

Radiological assessment of the placement of Essure® in order to reduce hysterosalpingography: Pelvic X-ray versus combined pelvic X-ray and ultrasound.

Science.gov (United States)

Petit, C; Vernet, T; Verpillat, P; Rubod, C; Cosson, M; Giraudet, G

2017-10-01

Three months after hysteroscopic sterilisation with Essure ® , a confirmation test is required to evaluate the correct location of the inserts. The test may be conducted using a pelvic ultrasound (2D or 3D) or an abdominal X-ray. Should the location not look satisfactory on these tests, a follow-up hysterosalpingography (HSG) would be required. The objective of our study is to assess whether the Essure ® 3-month confirmation test using a single X-ray or a combination of X-ray and ultrasound could reduce the use of HSG. This retrospective study examined patients who underwent birth control Essure ® procedure between 2009 and 2015 in the Gynaecological Surgery Department at the Regional University Hospital Centre (CHRU) in Lille. We divided patients into two groups based on the imaging tests performed: single X-ray (2009-2010) versus X-ray and pelvic ultrasound (2014-2015). We then compared the results of the imaging tests and the use of HSG between the two groups. One hundred and thirty-four patients were tested, of which 60 (44.8%) using a single X-ray and 74 (55.2%) using a combination of X-ray and ultrasound. We note that the combined X-ray/ultrasound test reduces significantly the number of HSG performed (26.7% versus 12.2%, P=0.04). Compared to a single X-ray, the combination of X-ray and ultrasound enables to significantly limit the use of HSG. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sagittal synostosis in X-linked hypophosphatemic rickets and related diseases

Energy Technology Data Exchange (ETDEWEB)

Currarino, Guido [Texas Scottish Rite Hospital, Department of Radiology, Dallas, TX (United States)

2007-08-15

The recent observations of two new cases of X-linked hypophosphatemic rickets associated with premature closure of the sagittal suture prompted a review of similar cases seen in this institution. To review the clinical records and skull radiographs of 28 children with hypophosphatemic rickets in order to investigate the frequency and type of craniosynostosis and other cranial vault changes seen in these conditions and to review the literature for relevant findings. Clinical and imaging records were reviewed on 28 patients with hypophosphatemic rickets, all younger than 18 years. Most patients had X-linked hypophosphatemic rickets and a few had autosomal-dominant hypophosphatemic rickets or were non-familial cases. Of the 28 patients, 13 had sagittal synostosis. Dolichocephaly was present in ten patients. The configuration of the cranial vault in some of these ten patients with dolichocephaly varied somewhat from that seen in nonsyndromic sagittal synostosis. In one patient, a Chiari I malformation was demonstrated by MRI. In another patient with increased intracranial pressure the sagittal suture closure was associated with lambdoidal synostosis. Dolichocephaly was not present in three patients, suggesting that the synostosis started later than in the other patients, probably in the second year of life, a period of slower brain growth than in the first year. The two patients in this group of three showed thickening and sclerosis of the cranial vault of uncertain etiology. There is an increased risk of sagittal synostosis in hypophosphatemic rickets and related diseases in children. The appearance of the cranial vault in this type of synostosis can vary from that seen in nonsyndromic synostosis. In this setting, careful clinical and imaging follow-up is warranted. (orig.)

Sagittal synostosis in X-linked hypophosphatemic rickets and related diseases

International Nuclear Information System (INIS)

Currarino, Guido

2007-01-01

The recent observations of two new cases of X-linked hypophosphatemic rickets associated with premature closure of the sagittal suture prompted a review of similar cases seen in this institution. To review the clinical records and skull radiographs of 28 children with hypophosphatemic rickets in order to investigate the frequency and type of craniosynostosis and other cranial vault changes seen in these conditions and to review the literature for relevant findings. Clinical and imaging records were reviewed on 28 patients with hypophosphatemic rickets, all younger than 18 years. Most patients had X-linked hypophosphatemic rickets and a few had autosomal-dominant hypophosphatemic rickets or were non-familial cases. Of the 28 patients, 13 had sagittal synostosis. Dolichocephaly was present in ten patients. The configuration of the cranial vault in some of these ten patients with dolichocephaly varied somewhat from that seen in nonsyndromic sagittal synostosis. In one patient, a Chiari I malformation was demonstrated by MRI. In another patient with increased intracranial pressure the sagittal suture closure was associated with lambdoidal synostosis. Dolichocephaly was not present in three patients, suggesting that the synostosis started later than in the other patients, probably in the second year of life, a period of slower brain growth than in the first year. The two patients in this group of three showed thickening and sclerosis of the cranial vault of uncertain etiology. There is an increased risk of sagittal synostosis in hypophosphatemic rickets and related diseases in children. The appearance of the cranial vault in this type of synostosis can vary from that seen in nonsyndromic synostosis. In this setting, careful clinical and imaging follow-up is warranted. (orig.)

Molecular analysis of T-B-NK+ severe combined immunodeficiency and Omenn syndrome cases in Saudi Arabia

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Al-Kayal Fadi

2009-11-01

Full Text Available Abstract Background Children with Severe Combined Immunodeficiency (SCID lack autologous T lymphocytes and present with multiple infections early in infancy. Omenn syndrome is characterized by the sole emergence of oligoclonal auto-reactive T lymphocytes, resulting in erythroderma and enteropathy. Omenn syndrome (OS shares the genetic aetiology of T-B-NK+ SCID, with mutations in RAG1, RAG2, or DCLRE1C. Methods Patients diagnosed with T-B-NK+ SCID or phenotypes suggestive of Omenn syndrome were investigated by molecular genetic studies using gene tightly linked microsatellite markers followed by direct sequencing of the coding regions and splice sites of the respective candidate genes. Results We report the molecular genetic basis of T-B-NK+ SCID in 22 patients and of OS in seven patients all of Arab descent from Saudi Arabia. Among the SCID patients, six (from four families displayed four homozygous missense mutations in RAG1 including V433M, R624H, R394W, and R559S. Another four patients (from three familes showed 3 novel homozygous RAG2 mutations including K127X, S18X, and Q4X; all of which predict unique premature truncations of RAG2 protein. Among Omenn patients, four (from two families have S401P and R396H mutations in RAG1, and a fifth patient has a novel I444M mutation in RAG2. Seven other patients (six SCID and one OS showed a gross deletion in exons 1-3 in DCLRE1C. Altogether, mutations in RAG1/2 and DCLRE1C account for around 50% and 25%, respectively, in our study cohort, a proportion much higher than in previous reported series. Seven (24% patients lack a known genetic aetiology, strongly suggesting that they carry mutations in novel genes associated with SCID and Omenn disorders that are yet to be discovered in the Saudi population. Conclusion Mutation-free patients who lack a known genetic aetiology are likely to carry mutations in the regulatory elements in the SCID-causing genes or in novel genes that are yet to be discovered

Electron microscopic studies on experimental skin cancer after combination treatment with X-ray, hematoporphyrin oligomer and caffeine

International Nuclear Information System (INIS)

Ueda, Keiichi; Ishiguro, Kazumori; Takaishi, Kimiko; Hatcho, Masahiro; Nakagawa, Shigemori

1992-01-01

The effect of combination treatment with X-ray, hematoporphyrin oligomer (HpO) and caffeine (Caf) was compared electron microscopically with that of a single use of these treatments. In experimental skin cancer, ultrastructural changes of nuclei and cytoplasm of tumor cells after combination treatment with HpO, X-ray and Caf showed more remarkable changes than in single X-ray irradiation and in HpO and X-ray irradiation. It is concluded that the combination treatment of HpO, X-ray and Caf is useful to the skin cancers in clinical practice. (author)

Electron microscopic studies on experimental skin cancer after combination treatment with X-ray, hematoporphyrin oligomer and caffeine

Energy Technology Data Exchange (ETDEWEB)

Ueda, Keiichi; Ishiguro, Kazumori; Takaishi, Kimiko; Hatcho, Masahiro; Nakagawa, Shigemori (Fukui Medical School, Matsuoka (Japan))

1992-05-01

The effect of combination treatment with X-ray, hematoporphyrin oligomer (HpO) and caffeine (Caf) was compared electron microscopically with that of a single use of these treatments. In experimental skin cancer, ultrastructural changes of nuclei and cytoplasm of tumor cells after combination treatment with HpO, X-ray and Caf showed more remarkable changes than in single X-ray irradiation and in HpO and X-ray irradiation. It is concluded that the combination treatment of HpO, X-ray and Caf is useful to the skin cancers in clinical practice. (author).

Sex-linked dominant

Science.gov (United States)

Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

DIA1R is an X-linked gene related to Deleted In Autism-1.

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Azhari Aziz

Full Text Available BACKGROUND: Autism spectrum disorders (ASDS are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1 gene. METHODOLOGY/PRINCIPAL FINDINGS: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related. While DIA1 is autosomal (chromosome 3, position 3q24, DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical, and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. CONCLUSIONS/SIGNIFICANCE: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.

Sex-specific expression of the X-linked histone demethylase gene Jarid1c in brain.

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Jun Xu

Full Text Available Jarid1c, an X-linked gene coding for a histone demethylase, plays an important role in brain development and function. Notably, JARID1C mutations cause mental retardation and increased aggression in humans. These phenotypes are consistent with the expression patterns we have identified in mouse brain where Jarid1c mRNA was detected in hippocampus, hypothalamus, and cerebellum. Jarid1c expression and associated active histone marks at its 5'end are high in P19 neurons, indicating that JARID1C demethylase plays an important role in differentiated neuronal cells. We found that XX mice expressed Jarid1c more highly than XY mice, independent of their gonadal types (testes versus ovaries. This increased expression in XX mice is consistent with Jarid1c escape from X inactivation and is not compensated by expression from the Y-linked paralogue Jarid1d, which is expressed at a very low level compared to the X paralogue in P19 cells. Our observations suggest that sex-specific expression of Jarid1c may contribute to sex differences in brain function.

Dysregulation of X-Linked Gene Expression in Klinefelter’s Syndrome and Association With Verbal Cognition

Science.gov (United States)

Vawter, Marquis P.; Harvey, Philip D.; DeLisi, Lynn E.

2007-01-01

Klinefelter’s Syndrome (KS) is a chromosomal karyotype with one or more extra X chromosomes. KS individuals often show language impairment and the phenotype might be due to overexpression of genes on the extra X chromosome(s). We profiled mRNA derived from lymphoblastoid cell lines from males with documented KS and control males using the Affymetrix U133P microarray platform. There were 129 differentially expressed genes (DEGs) in KS group compared with controls after Benjamini–Hochberg false discovery adjustment. The DEGs included 14 X chromosome genes which were significantly over-represented. The Y chromosome had zero DEGs. In exploratory analysis of gene expression–cognition relationships, 12 DEGs showed significant correlation of expression with measures of verbal cognition in KS. Overexpression of one pseudoautosomal gene, GTPBP6 (GTP binding protein 6, putative) was inversely correlated with verbal IQ (r = −0.86, P < 0.001) and four other measures of verbal ability. Overexpression of XIST was found in KS compared to XY controls suggesting that silencing of many genes on the X chromosome might occur in KS similar to XX females. The microarray findings for eight DEGs were validated by quantitative PCR. The 14 X chromosome DEGs were not differentially expressed in prior studies comparing female and male brains suggesting a dysregulation profile unique to KS. Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition–gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function. A screen of candidate genes may serve as biomarkers of KS for early diagnosis. PMID:17347996

Effect of pancreatic kallikrein combined with magnesium sulfate therapy on disease severity of patients with severe preeclampsia

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Yi Yang

2016-10-01

Full Text Available Objective: To study the clinical effect of pancreatic kallikrein combined with magnesium sulfate therapy on severe preeclampsia. Methods: A total of 47 patients with severe preeclampsia treated in our hospital from May 2013 to October 2015 were retrospectively analyzed, patients who received pancreatic kallikrein combined with magnesium sulfate therapy were selected as observation group, patients who received magnesium sulfate therapy were selected as control group, and then blood pressure level, renal function, uterine artery and umbilical artery blood flow state, and hypoxia indexes in serum and placenta were compared between two groups. Results: After treatment, systolic pressure and diastolic pressure levels as well as serum CysC level and 24 h urine protein level of observation group were significantly lower than those of control group, the uterine artery and umbilical artery S/ D and PI were significantly lower than those of control group, PIGF and NO levels in serum as well as Xiap and Survivin levels in placenta were significantly higher than those of control group, and sVEGFR1 level in serum as well as Caspase-3 and Caspase-7 levels in placenta was significantly lower than those of control group. Conclusions: Pancreatic kallikrein combined with magnesium sulfate therapy can alleviate the disease severity, lower blood pressure and vascular resistance, and improve renal function and the apoptosis caused by placental hypoxia in patients with severe preeclampsia.

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect.

Science.gov (United States)

Ravell, Juan; Chaigne-Delalande, Benjamin; Lenardo, Michael

2014-12-01

To describe the role of the magnesium transporter 1 (MAGT1) in the pathogenesis of 'X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia' (XMEN) disease and its clinical implications. The magnesium transporter protein MAGT1 participates in the intracellular magnesium ion (Mg) homeostasis and facilitates a transient Mg influx induced by the activation of the T-cell receptor. Loss-of-function mutations in MAGT1 cause an immunodeficiency named 'XMEN syndrome', characterized by CD4 lymphopenia, chronic EBV infection, and EBV-related lymphoproliferative disorders. Patients with XMEN disease have impaired T-cell activation and decreased cytolytic function of natural killer (NK) and CD8 T cells because of decreased expression of the NK stimulatory receptor 'natural-killer group 2, member D' (NKG2D). Patients may have defective specific antibody responses secondary to T cell dysfunction, but B cells have not been shown to be directly affected by mutations in MAGT1. XMEN disease has revealed a novel role for free intracellular magnesium in the immune system. Further understanding of the MAGT1 signaling pathway may lead to new diagnostic and therapeutic approaches.

Severe recurrent achalasia cardia responding to treatment of severe autoimmune acquired haemophilia

OpenAIRE

Al-Jafar, H; Laffan, M; Al-Sabah, S; Elmorsi, M; Habeeb, M; Alnajar, F

2012-01-01

Acquired haemophilia A and severe acquired achalasia are both very rare conditions with unknown aetiology. Haemophilia A is a haemorrhagic disease induced by deficiency or malfunction of coagulation factor VIII. Congenital haemophilia is an inherited disease transmitted by the mother through X-linked inheritance and primarily affects males. However, acquired haemophilia A is a serious, sudden-onset, autoimmune disease that affects either sex. In addition, achalasia is a disease of the oesopha...

Dosage compensation and demasculinization of X chromosomes in Drosophila.

Science.gov (United States)

Bachtrog, Doris; Toda, Nicholas R T; Lockton, Steven

2010-08-24

The X chromosome of Drosophila shows a deficiency of genes with male-biased expression, whereas mammalian X chromosomes are enriched for spermatogenesis genes expressed premeiosis and multicopy testis genes. Meiotic X-inactivation and sexual antagonism can only partly account for these patterns. Here, we show that dosage compensation (DC) in Drosophila may contribute substantially to the depletion of male genes on the X. To equalize expression between X-linked and autosomal genes in the two sexes, male Drosophila hypertranscribe their single X, whereas female mammals silence one of their two X chromosomes. We combine fine-scale mapping data of dosage compensated regions with genome-wide expression profiles and show that most male-biased genes on the D. melanogaster X are located outside dosage compensated regions. Additionally, X-linked genes that have newly acquired male-biased expression in D. melanogaster are less likely to be dosage compensated, and parental X-linked genes that gave rise to an autosomal male-biased retrocopy are more likely located within compensated regions. This suggests that DC contributes to the observed demasculinization of X chromosomes in Drosophila, both by limiting the emergence of male-biased expression patterns of existing X genes, and by contributing to gene trafficking of male genes off the X. Copyright 2010 Elsevier Ltd. All rights reserved.

Nonspecific X-linked mental retardation with macrocephaly and obesity: A further family

Energy Technology Data Exchange (ETDEWEB)

Baraitser, M.; Reardon, W. [Hospital for Sick Children, London (United Kingdom); Vijeratnam, S. [Highlands Hospital, London (United Kingdom)

1995-07-03

The phenotypic nonspecificity of many forms of X-linked mental retardation has hampered attempts to classify them into clinically homogeneous groups. One such condition, described by Clark and Baraitser, has been the subject of a single pedigree report to date. We now describe a further pedigree whose affected members share many manifestations with those reported by Clark and Baraitser, and we consider the possible distinction between this condition and Atkin-Flaitz syndrome. 9 refs., 4 figs., 1 tab.

The combination of an industrial X-ray-film with a vacuum-adapter instead of a foil-less industrial X-ray-film

International Nuclear Information System (INIS)

Kurz, C.S.; Rotte, K.

1980-01-01

In clinical routine it was proved, how far an industrial X-ray-film in combination with the low-dose-system gives the same evidence as an foil-less industrial X-ray-film. Patients which had got in the past a mammography at both sides with a foil-less industrial X-ray-film received a mammography at both sides with the low-dose-system. Both X-rays were compared in the following criteria: artefacts, micro-calcifications, structure-differentiation, difinition, contrast, exposure, time of diagnosis and overal impression. Considering an evident dose reduction by the low-dose-system the result is, that a film-foil-combination with a vacuum-adapter is available without impairment of diagnostic evidence in clinical routine. (orig.) [de

Structure cristalline du composé Hg3-xSbx(S+Se2+xI2-x (x ≃ 0.1

Directory of Open Access Journals (Sweden)

Mohammed Kars

2016-03-01

Full Text Available Single crystals of the mercury chalcohalide Hg3-xSbx(S+Se2+xI2-x (x ≃ 0.1 (mercury antimony sulfide selenide iodide, were grown by a chemical transport reaction. The structure contains three independent A (Hg/Sb atoms; each atom is strongly covalently bonded with two X (Se/S atoms to form approximately linear X–A–X units. The X–A–X units link to form A4X4 rings, which are combined into infinite crankshaft-type bands running along the [100] direction. Four equatorial E (I/X = Se,S atoms at relatively long distances complete the distorted octahedral coordination of A (Hg/Sb. The crystal under investigation was twinned by non-merohedry with a refined twin domain fraction of 0.814 (6:0.186 (6. The structure is isotypic with Hg3Se2I2 [Beck & Hedderich (2000. J. Solid State Chem. 151, 73–76], but the current determination reveals a coupled substitution, with partial replacement of Hg+2 by Sb+3, balanced by the equivalent substitution of I−1 by S−2 and Se−2. Bond-valence calculations are consistent with this relative substitution model.

Combined synthetic x-ray and radio observations of simulated radio jets

Energy Technology Data Exchange (ETDEWEB)

Tregillis, I. L. (Ian L.); Jones, T. W. (Thomas Walter),; Ryu, Dongsu

2004-01-01

We present results from an extensive synthetic observation analysis of numerically-simulated radio galaxy jets. This is the first such analysis to be based on simulations with sufficient physical detail to allow the application of standard observational analysis techniques to simulated radio galaxies. Here we focus on extracting magnetic field properties from nonthermal intensity information. We study field values obtained via the combination of synchrotron radio and inverse-Compton X-ray data as well as those from the minimum-energy approach. The combined radio/X-ray technique provides meaningful information about the field. The minimum-energy approach retrieves reasonable field estimates in regions physically close to the minimum-energy partitioning, though the technique is highly susceptible to deviations from the underlying assumptions. We also look at how the two field measurement techniques might be combined to provide a rough measure of the actual energy in particles and fields. A full report on this work can be found in the Astrophysical Journal, v601, p778.

X-linked deafness, stapes gushers and a distinctive defect of the inner ear

Energy Technology Data Exchange (ETDEWEB)

Phelps, P.D. (Royal National Throat, Nose and Ear Hospital, London (United Kingdom)); Reardon, W.; Pembrey, M. (Institute of Child Health, London (United Kingdom)); Bellman, S. (Hospital for Sick Children, London (United Kingdom)); Luxom, L. (National Hospital for Neurology and Neurosurgery, London (United Kingdom))

1991-08-01

We have made genetic linkage studies in 7 pedigrees in whom deafness was inherited in an X-linked manner. All patients had a full range of audiometric and vestibular function tests. Thin section high resolution CT in two planes was used to assess the state of the middle and inner ears. We found a distinctive inner ear deformity in some of the deaf males. Moreover, some of the obligate feamle carriers seem to have a milder form of the same anomaly associated with slight hearing loss. Genetic studies on some of the deaf males with apparently normal inner ear anatomy suggest a different locus on the X chromosome and hence a different pathogenesis for the deafness. (orig./GDG).

X-linked deafness, stapes gushers and a distinctive defect of the inner ear

International Nuclear Information System (INIS)

Phelps, P.D.; Reardon, W.; Pembrey, M.; Bellman, S.; Luxom, L.

1991-01-01

We have made genetic linkage studies in 7 pedigrees in whom deafness was inherited in an X-linked manner. All patients had a full range of audiometric and vestibular function tests. Thin section high resolution CT in two planes was used to assess the state of the middle and inner ears. We found a distinctive inner ear deformity in some of the deaf males. Moreover, some of the obligate feamle carriers seem to have a milder form of the same anomaly associated with slight hearing loss. Genetic studies on some of the deaf males with apparently normal inner ear anatomy suggest a different locus on the X chromosome and hence a different pathogenesis for the deafness. (orig./GDG)

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism.

Science.gov (United States)

Tronnier, V M; Domingo, A; Moll, C K; Rasche, D; Mohr, C; Rosales, R; Capetian, P; Jamora, R D; Lee, L V; Münchau, A; Diesta, C C; Tadic, V; Klein, C; Brüggemann, N; Moser, A

2015-08-01

Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gastric adenocarcinoma in a patient with X-linked agammaglobulinemia and HIV: Case report and review of the literature

Directory of Open Access Journals (Sweden)

Joud Hajjar

2016-09-01

Full Text Available X-linked agammaglobulinemia (XLA is an X-linked inherited disease usually caused by a germline mutation in the BTK gene leading to Bruton’s tyrosine kinase deficiency, which results in the impaired development of B-lymphocytes and a subsequent lack of immunoglobulin production. Patients with XLA have an increased susceptibility to bacterial and viral infections, and multiple case reports have been published regarding an association between XLA and gastrointestinal (GI malignancy. Here, we describe a case of a 25-year-old man with XLA and HIV, who developed gastric adenocarcinoma. Previously reported cases of XLA and GI malignancy are also reviewed and summarized.

Exonization of a LINE1 fragment implicated in X-linked hypohidrotic ectodermal dysplasia in cattle

DEFF Research Database (Denmark)

Karlskov-Mortensen, Peter; Cirera Salicio, Susanna; Nielsen, Ole Lerberg

2011-01-01

A case of X-linked hypohidrotic ectodermal dysplasia (XHED) was identified in a family of Danish Red Holstein cattle. The ectodysplasin-signalling protein (EDA) is known to be central in the normal development of ectodermal structures, and mutations in the ectodysplasin A (EDA) gene have been rep...

Severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia.

Science.gov (United States)

Scott, Angela; Glover, Jason; Skoda-Smith, Suzanne; Torgerson, Troy R; Xu, Min; Burroughs, Lauri M; Woolfrey, Ann E; Fleming, Mark D; Shimamura, Akiko

2015-11-01

Aplastic anemia in the neonate is rare. We report a case of severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia. This report highlights the importance of considering SCID early in the evaluation of neonatal aplastic anemia prior to the development of infectious complications. © 2015 Wiley Periodicals, Inc.

The combined effects of MRI and X-radiation on ICR mouse embryos during organogenesis

International Nuclear Information System (INIS)

Gu, Y.H.; Hasegawa, T.; Yamamoto, Y.; Mori, T.; Bamen, K.; Iwasa, T.; Kai, M.; Kusama, T.

2000-01-01

The combined effects of X-radiation magnetic resonance imaging (MRI) malformations, fetal body weight and sex ratios of mice treated on day 8 of gestation were determined at day 18 of gestation. These were no significant differences in the frequency of prenatal death, fetal body weight and sex ratios between control and 0.5 T irradiated mice. The frequencies of embryonic deaths in mice irradiated with X-rays increased significantly. The frequencies of external malformations such as exencephaly and anophthalmia in mice irradiated with X-rays or MRI increased significantly. However the frequencies of external malformation and prenatal death in the mice irradiated with both X-rays and MRI decreased more than in mice irradiated with X-rays alone. The combined effects of radiation and MRI on the external malformations and embryonic death might be antagonistic. (author)

The combined effects of MRI and X-radiation on ICR mouse embryos during organogenesis

Energy Technology Data Exchange (ETDEWEB)

Gu, Y.H.; Hasegawa, T.; Yamamoto, Y.; Mori, T. [Suzuka University of Medical Science, Department of Radiological Technology, Suzuka, Mie (Japan); Bamen, K.; Iwasa, T. [Oita University of Nursing and Health Sciences, Department of Health Science, Oita (Japan); Kai, M.; Kusama, T. [Bio Queen Co., Ltd., Tokyo (Japan)

2000-05-01

The combined effects of X-radiation magnetic resonance imaging (MRI) malformations, fetal body weight and sex ratios of mice treated on day 8 of gestation were determined at day 18 of gestation. These were no significant differences in the frequency of prenatal death, fetal body weight and sex ratios between control and 0.5 T irradiated mice. The frequencies of embryonic deaths in mice irradiated with X-rays increased significantly. The frequencies of external malformations such as exencephaly and anophthalmia in mice irradiated with X-rays or MRI increased significantly. However the frequencies of external malformation and prenatal death in the mice irradiated with both X-rays and MRI decreased more than in mice irradiated with X-rays alone. The combined effects of radiation and MRI on the external malformations and embryonic death might be antagonistic. (author)

Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

Science.gov (United States)

Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular, and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and fou...

Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice

International Nuclear Information System (INIS)

Yasui, Hironobu; Inanami, Osamu; Asanuma, Taketoshi; Iizuka, Daisuke; Nakajima, Takayuki; Kon, Yasuhiro; Matsuda, Akira; Kuwabara, Mikinori

2007-01-01

Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth

X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face

NARCIS (Netherlands)

Harakalova, Magdalena; van den Boogaard, Marie-Jose; Sinke, Richard; van Lieshout, Stef; van Tuil, Marc C.; Duran, Karen; Renkens, Ivo; Terhal, Paulien A.; de Kovel, Carolien; Nijman, Ies J.; van Haelst, Mieke; Knoers, Nine V. A. M.; van Haaften, Gijs; Kloosterman, Wigard; Hennekam, Raoul C. M.; Cuppen, Edwin; van Amstel, Hans Kristian Ploos

Background We present a large Dutch family with seven males affected by a novel syndrome of X-linked intellectual disability, hypogonadism, gynaecomastia, truncal obesity, short stature and recognisable craniofacial manifestations resembling but not identical to Wilson-Turner syndrome. Seven female

X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face

NARCIS (Netherlands)

Harakalova, Magdalena; van den Boogaard, Marie-Jose; Sinke, Richard; van Lieshout, Stef; van Tuil, Marc C.; Duran, Karen; Renkens, Ivo; Terhal, Paulien A.; de Kovel, Carolien; Nijman, Ies J.; van Haelst, Mieke; Knoers, Nine V. A. M.; van Haaften, Gijs; Kloosterman, Wigard; Hennekam, Raoul C. M.; Cuppen, Edwin; Ploos van Amstel, Hans Kristian

2012-01-01

Background We present a large Dutch family with seven males affected by a novel syndrome of X-linked intellectual disability, hypogonadism, gynaecomastia, truncal obesity, short stature and recognisable craniofacial manifestations resembling but not identical to Wilson-Turner syndrome. Seven female

X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face

NARCIS (Netherlands)

Harakalova, M.; van den Boogaard, M.J.; Sinke, R.; van Lieshout, S.; van Tuil, M.C.; Duran, K.; Renkens, I.; Terhal, P.A.; de Kovel, C.; Nijman, I.J.; van Haelst, M.; Knoers, N.V.; van Haaften, G.; Kloosterman, W.; Hennekam, R.C.; Cuppen, E.; Ploos van Amstel, H.K.

2012-01-01

BACKGROUND: We present a large Dutch family with seven males affected by a novel syndrome of X-linked intellectual disability, hypogonadism, gynaecomastia, truncal obesity, short stature and recognisable craniofacial manifestations resembling but not identical to Wilson-Turner syndrome. Seven female

Regulatory divergence of X-linked genes and hybrid male sterility in mice.

Science.gov (United States)

Oka, Ayako; Shiroishi, Toshihiko

2014-01-01

Postzygotic reproductive isolation is the reduction of fertility or viability in hybrids between genetically diverged populations. One example of reproductive isolation, hybrid male sterility, may be caused by genetic incompatibility between diverged genetic factors in two distinct populations. Genetic factors involved in hybrid male sterility are disproportionately located on the X chromosome. Recent studies showing the evolutionary divergence in gene regulatory networks or epigenetic effects suggest that the genetic incompatibilities occur at much broader levels than had previously been thought (e.g., incompatibility of protein-protein interactions). The latest studies suggest that evolutionary divergence of transcriptional regulation causes genetic incompatibilities in hybrid animals, and that such incompatibilities preferentially involve X-linked genes. In this review, we focus on recent progress in understanding hybrid sterility in mice, including our studies, and we discuss the evolutionary significance of regulatory divergence for speciation.

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations.

Science.gov (United States)

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10-13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease.

Methyldopa combined with prindolol in the treatment of severe ...

African Journals Online (AJOL)

In a clinical trial of 30 patients suffering from severe hypertension (diastolic blood pressure above 130 mmHg) the combination of methyldopa and prindolol produced a satisfactory drop in blood pressure; a further 2 patients were satisfactorily controlled with the addition of furosemide 40 mg daily. Side-effects were few, and ...

Combining operando synchrotron X-ray tomographic microscopy and scanning X-ray diffraction to study lithium ion batteries

Science.gov (United States)

Pietsch, Patrick; Hess, Michael; Ludwig, Wolfgang; Eller, Jens; Wood, Vanessa

2016-06-01

We present an operando study of a lithium ion battery combining scanning X-ray diffraction (SXRD) and synchrotron radiation X-ray tomographic microscopy (SRXTM) simultaneously for the first time. This combination of techniques facilitates the investigation of dynamic processes in lithium ion batteries containing amorphous and/or weakly attenuating active materials. While amorphous materials pose a challenge for diffraction techniques, weakly attenuating material systems pose a challenge for attenuation-contrast tomography. Furthermore, combining SXRD and SRXTM can be used to correlate processes occurring at the atomic level in the crystal lattices of the active materials with those at the scale of electrode microstructure. To demonstrate the benefits of this approach, we investigate a silicon powder electrode in lithium metal half-cell configuration. Combining SXRD and SRXTM, we are able to (i) quantify the dissolution of the metallic lithium electrode and the expansion of the silicon electrode, (ii) better understand the formation of the Li15Si4 phase, and (iii) non-invasively probe kinetic limitations within the silicon electrode. A simple model based on the 1D diffusion equation allows us to qualitatively understand the observed kinetics and demonstrates why high-capacity electrodes are more prone to inhomogeneous lithiation reactions.

Combining operando synchrotron X-ray tomographic microscopy and scanning X-ray diffraction to study lithium ion batteries

Science.gov (United States)

Pietsch, Patrick; Hess, Michael; Ludwig, Wolfgang; Eller, Jens; Wood, Vanessa

2016-01-01

We present an operando study of a lithium ion battery combining scanning X-ray diffraction (SXRD) and synchrotron radiation X-ray tomographic microscopy (SRXTM) simultaneously for the first time. This combination of techniques facilitates the investigation of dynamic processes in lithium ion batteries containing amorphous and/or weakly attenuating active materials. While amorphous materials pose a challenge for diffraction techniques, weakly attenuating material systems pose a challenge for attenuation-contrast tomography. Furthermore, combining SXRD and SRXTM can be used to correlate processes occurring at the atomic level in the crystal lattices of the active materials with those at the scale of electrode microstructure. To demonstrate the benefits of this approach, we investigate a silicon powder electrode in lithium metal half-cell configuration. Combining SXRD and SRXTM, we are able to (i) quantify the dissolution of the metallic lithium electrode and the expansion of the silicon electrode, (ii) better understand the formation of the Li15Si4 phase, and (iii) non-invasively probe kinetic limitations within the silicon electrode. A simple model based on the 1D diffusion equation allows us to qualitatively understand the observed kinetics and demonstrates why high-capacity electrodes are more prone to inhomogeneous lithiation reactions. PMID:27324109

Drugs + HIV, Learn the Link

Medline Plus

Full Text Available ... projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

Neuroleptic malignant syndrome during zuclopenthixol therapy in X-linked cerebral adrenoleukodystrophy.

NARCIS (Netherlands)

Rubio Gozalbo, M.E.; Waardenburg, D.A. van; Forget, P.P.; Spaapen, L.J.; Verrips, A.; Vroomen, P.C.

2001-01-01

An 8 year-old boy with X-ALD under treatment with simvastatin developed a severe adverse reaction when the dose of his other medication, zuclopenthixol was increased. Both drugs were withdrawn after a diagnosis of neuroleptic malignant syndrome was made.

Impact of corneal cross-linking combined with photorefractive keratectomy on blurring strength

OpenAIRE

Labiris, Georgios; Sideroudi, Haris; Angelonias, Dimitris; Georgantzoglou, Kimonas; Kozobolis, Vassilios P

2016-01-01

Georgios Labiris,1,2 Haris Sideroudi,2 Dimitris Angelonias,2 Kimonas Georgantzoglou,2 Vassilios P Kozobolis1,21Department of Ophthalmology, University Hospital of Alexandroupolis, 2Eye Institute of Thrace, Alexandroupolis, GreecePurpose: The aim of this study was to evaluate the impact of corneal cross-linking combined with photorefractive keratectomy (PRK) on blurring strength.Methods: A total of 63 patients with keratoconus were recruited for this study, and two study groups were formed acc...

Drugs + HIV, Learn the Link

Medline Plus

Full Text Available ... site. Please link these banners back to this site at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to ...

The contribution of color to visual memory in X-chromosome-linked dichromats.

Science.gov (United States)

Gegenfurtner, K R; Wichmann, F A; Sharpe, L T

1998-04-01

We used a recognition memory paradigm to assess the visual memory of X-chromosome-linked dichromats for color images of natural scenes. The performance of 17 protanopes and 14 deuteranopes, who lack the second (red-green opponent) subsystem of color vision, but retain the primordial (yellow-blue opponent) subsystem, was compared with that of 36 color normal observers. During the presentation phase, 48 images of natural scenes were displayed on a CRT for durations between 50 and 1000 msec. Each image was followed by a random noise mask. Half of the images were presented in color and half in black and white. In the subsequent query phase, the same 48 images were intermixed with 48 new images and the subjects had to indicate which of the images they had already seen during the presentation phase. We find that the performance of the color normal observers increases with exposure duration. However, they perform 5-10% better for colored than for black and white images, even at exposure durations as short as 50 msec. Surprisingly, performance is not impaired for the dichromats, whose recognition performance is also better for colored than for black and white images. We conclude either that X-chromosome-linked dichromats may be able to compensate for their reduced chromatic information range when viewing complex natural scenes or that the chromatic information in most natural scenes, for the durations tested, is sufficiently represented by the surviving primordial color subsystem.

Drugs + HIV, Learn the Link

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Full Text Available ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to parents, teachers, and the media about the link between drug ...

Dental management of patients with X-linked hypophosphatemia

Directory of Open Access Journals (Sweden)

Bin-Na Lee

2017-05-01

Full Text Available X-linked hypophosphatemia (XLH is a hereditary metabolic disease caused by the loss of phosphate through the renal tubules into the urine, and an associated decrease in serum calcium and potassium phosphate. Its dental features include spontaneous dental abscesses that occur in the absence of trauma or dental caries. The aim of this case report was to describe the dental problems of XLH patients and to evaluate limitations in their treatment. A 14 year old male and a 38 year old female with XLH were referred to the Department of Conservative Dentistry for endodontic treatment. The dental findings were periapical abscesses without obvious trauma or caries. Conservative endodontic treatment was performed in teeth with pulp necrosis and abscess. In case 1, the treated teeth showed improvements in bone healing, without clinical symptoms. However, in case 2, the implants and the treated tooth showed hypermobility, and the final restoration was therefore postponed. Early diagnosis, periodic examinations, and communication with the patient's pediatrician are important in the dental management of patients with XLH

Combined Application of QEM-SEM and Hard X-ray Microscopy to Determine Mineralogical Associations and Chemcial Speciation of Trace Metals

Energy Technology Data Exchange (ETDEWEB)

M Grafe; M Landers; R Tappero; P Austin; B Gan; A Grabsch; C Klauber

2011-12-31

We describe the application of quantitative evaluation of mineralogy by scanning electron microscopy in combination with techniques commonly available at hard X-ray microprobes to define the mineralogical environment of a bauxite residue core segment with the more specific aim of determining the speciation of trace metals (e.g., Ti, V, Cr, and Mn) within the mineral matrix. Successful trace metal speciation in heterogeneous matrices, such as those encountered in soils or mineral residues, relies on a combination of techniques including spectroscopy, microscopy, diffraction, and wet chemical and physical experiments. Of substantial interest is the ability to define the mineralogy of a sample to infer redox behavior, pH buffering, and mineral-water interfaces that are likely to interact with trace metals through adsorption, coprecipitation, dissolution, or electron transfer reactions. Quantitative evaluation of mineralogy by scanning electron microscopy coupled with micro-focused X-ray diffraction, micro-X-ray fluorescence, and micro-X-ray absorption near edge structure (mXANES) spectroscopy provided detailed insights into the composition of mineral assemblages and their effect on trace metal speciation during this investigation. In the sample investigated, titanium occurs as poorly ordered ilmenite, as rutile, and is substituted in iron oxides. Manganese's spatial correlation to Ti is closely linked to ilmenite, where it appears to substitute for Fe and Ti in the ilmenite structure based on its mXANES signature. Vanadium is associated with ilmenite and goethite but always assumes the +4 oxidation state, whereas chromium is predominantly in the +3 oxidation state and solely associated with iron oxides (goethite and hematite) and appears to substitute for Fe in the goethite structure.

Remote sensing of fire severity: linking post-fire reflectance data with physiological responses in two western conifer species

Science.gov (United States)

Sparks, A. M.; Smith, A. M.; Kolden, C.; Apostol, K. G.; Boschetti, L.

2014-12-01

Fire is a common disturbance in forested ecosystems in the western U.S. and can be responsible for long-term impacts on vegetation and soil. An improved understanding of how ecosystems recover after fire is necessary so that land managers can plan for and mitigate the effects of these disturbances. Although several studies have attempted to link fire intensity with severity, direct links between spectral indices of severity and key physiological changes in vegetation are not well understood. We conducted an assessment of how two western conifer species respond to four fire radiative energy treatments, with spectra acquired pre- and up to a month post-burn. After transforming the spectral data into Landsat 8 equivalent reflectance, burn severity indices commonly used in the remote sensing community were compared to concurrent physiological measurements including gas exchange and photosynthetic rate. Preliminary results indicate significant relationships between several fire severity indices and physiological responses measured in the conifer seedlings.

Mutation pattern in the Bruton's tyrosine kinase gene in 26 unrelated patients with X-linked agammaglobulinemia

DEFF Research Database (Denmark)

Vorechovský, I; Luo, L; Hertz, Jens Michael

1997-01-01

Mutation pattern was characterized in the Bruton's tyrosine kinase gene (BTK) in 26 patients with X-linked agammaglobulinemia, the first described immunoglobulin deficiency, and was related to BTK expression. A total of 24 different mutations were identified. Most BTK mutations were found to result...

Carrier detection in X-linked ocular albinism of the Nettleship-Falls type by DNA analysis

NARCIS (Netherlands)

Bergen, A. A.; Schuurman, E. J.; van den Born, L. I.; Samanns, C.; van Dorp, D. B.; Pinckers, A. J.; Bakker, E.; van Ommen, G. J.; Gal, A.; Bleeker-Wagemakers, E. M.

1992-01-01

X-linked ocular albinism (XOA) is characterized by anomalies of the eyes and hypopigmentation or absence of pigment in skin, hair and eyes due to a hereditary inborn error of metabolism affecting the pigment cells. The gene of XOA of the Nettleship-Falls type (OA1) has been mapped to Xp22.3, and

Novel and recurrent NDP gene mutations in familial cases of Norrie disease and X-linked exudative vitreoretinopathy.

Science.gov (United States)

Pelcastre, Erika L; Villanueva-Mendoza, Cristina; Zenteno, Juan C

2010-05-01

To present the results of molecular analysis of the NDP gene in Mexican families with Norrie disease (ND) and X-linked familial exudative vitreoretinopathy (XL-FEVR). Two unrelated families with ND and two with XL-FEVR were studied. Clinical diagnosis was suspected on the basis of a complete ophthalmologic examination. Molecular methods included DNA isolation from peripheral blood leucocytes, polymerase chain reaction amplification and direct nucleotide sequencing analysis of the complete coding region and exon-intron junctions of NDP. Haplotype analysis using NDP-linked microsatellites markers was performed in both ND families. A novel Norrin missense mutation, p.Arg41Thr, was identified in two apparently unrelated families with ND. Haplotype analysis demonstrated that affected males in these two families shared the same ND-linked haplotype, suggesting a common origin for this novel mutation. The previously reported p.Arg121Trp and p.Arg121Gln Norrin mutations were identified in the two families with XL-FEVR. Our results expand the mutational spectrum in ND. This is the first report of ND resulting from mutation at arginine position 41 of Norrin. Interestingly, mutations at the same residue but resulting in a different missense change were previously described in subjects with XL-FEVR (p.Arg41Lys) or persistent fetal vasculature syndrome (p.Arg41Ser), indicating that the novel p.Arg41Thr change causes a more severe retinal phenotype. Preliminary data suggest a founder effect for the ND p.Arg41Thr mutation in these two Mexican families.

Soft X-ray radio-sensitivities of pollens in several fruit species

International Nuclear Information System (INIS)

Hu Chungen; Deng Xiuxin

1996-01-01

Irradiated with different dosages of soft X-ray, pollen germinations of prunus baimang, pear kieffer, trifoliate orange and pummelo, were investigated immediately or several days later after irradiation. The results revealed that the pollens of these fruit tress had different sensitivites to soft X-ray and various responses to storage duration. Therefore, even to the same kind of pollen, irradiation with different optimal exposure doses, as well as pollination at different times during storage, should be adopted variously according to the different aims and methods of breeding programs. (author)

Wear performance of neat and vitamin E blended highly cross-linked PE under severe conditions: The combined effect of accelerated ageing and third body particles during wear test.

Science.gov (United States)

Affatato, Saverio; De Mattia, Jonathan Salvatore; Bracco, Pierangiola; Pavoni, Eleonora; Taddei, Paola

2016-12-01

The objective of this study is to evaluate the effects of third-body particles on the in vitro wear behaviour of three different sets of polyethylene acetabular cups after prolonged testing in a hip simulator and accelerated ageing. Vitamin E-blended, cross-linked polyethylene (XLPE_VE), cross-linked polyethylene (XLPE) and conventional polyethylene (STD_PE) acetabular cups were simulator tested for two million cycles under severe conditions (i.e. by adding third-body particles to the bovine calf serum lubricant). Micro-Fourier Transform Infrared and micro-Raman spectroscopic analyses, differential scanning calorimetry, and crosslink density measurements were used to characterize the samples at a molecular level. The STD_PE cups had twice mass loss than the XLPE_VE components and four times than the XLPE samples; statistically significant differences were found between the mass losses of the three sets of cups. The observed wear trend was justified on the basis of the differences in cross-link density among the samples (XLPE>XLPE_VE>STD_PE). FTIR crystallinity profiles, bulk DSC crystallinity and surface micro-Raman crystallinity seemed to have a similar behaviour upon testing: all of them (as well as the all-trans and ortho-trans contents) revealed the most significant changes in XLPE and XLPE_VE samples. The more severe third-body wear testing conditions determined more noticeable changes in all spectroscopic markers with respect to previous tests. Unexpectedly, traces of bulk oxidation were found in both STD_PE (unirradiated) and XLPE (remelting-stabilized), which were expected to be stable to oxidation; on the contrary, XLPE_VE demonstrated a high oxidative stability in the present, highly demanding conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1

NARCIS (Netherlands)

Jensen, L.R.; Chen, W.; Moser, B.; Lipkowitz, B.; Schroeder, C.; Musante, L.; Tzschach, A.; Kalscheuer, V.M.M.; Meloni, I.; Raynaud, M.; Esch, H. van; Chelly, J.; Brouwer, A.P. de; Hackett, A.; Haar, S. van der; Henn, W.; Gecz, J.; Riess, O.; Bonin, M.; Reinhardt, R.; Ropers, H.H.; Kuss, A.W.

2011-01-01

X-linked intellectual disability (XLID), also known as X-linked mental retardation, is a highly genetically heterogeneous condition for which mutations in >90 different genes have been identified. In this study, we used a custom-made sequencing array based on the Affymetrix 50k platform for mutation

Physiological Arousal in Autism and Fragile X Syndrome: Group Comparisons and Links with Pragmatic Language

Science.gov (United States)

Klusek, Jessica; Martin, Gary E.; Losh, Molly

2013-01-01

This study tested the hypothesis that pragmatic (i.e., social) language impairment is linked to arousal dysregulation in autism spectrum disorder (ASD) and fragile X syndrome (FXS). Forty boys with ASD, 39 with FXS, and 27 with typical development (TD), aged 4-15 years, participated. Boys with FXS were hyperaroused compared to boys with TD but did…

Educational paper: The expanding clinical and immunological spectrum of severe combined immunodeficiency

NARCIS (Netherlands)

M. van der Burg (Mirjam); A.R. Gennery (Andy R.)

2011-01-01

textabstractSevere combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical presentation varies from the classical

Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease

Science.gov (United States)

Bustamante, Jacinta; Arias, Andres A; Vogt, Guillaume; Picard, Capucine; Galicia, Lizbeth Blancas; Prando, Carolina; Grant, Audrey V; Marchal, Christophe C; Hubeau, Marjorie; Chapgier, Ariane; de Beaucoudrey, Ludovic; Puel, Anne; Feinberg, Jacqueline; Valinetz, Ethan; Jannière, Lucile; Besse, Céline; Boland, Anne; Brisseau, Jean-Marie; Blanche, Stéphane; Lortholary, Olivier; Fieschi, Claire; Emile, Jean-François; Boisson-Dupuis, Stéphanie; Al-Muhsen, Saleh; Woda, Bruce; Newburger, Peter E; Condino-Neto, Antonio; Dinauer, Mary C; Abel, Laurent; Casanova, Jean-Laurent

2011-01-01

Germline mutations in CYBB, the human gene encoding the gp91phox subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This ‘experiment of nature’ indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria. PMID:21278736

Assessment of single and combined X-ray and colchicine treatment on Trichosanthes anguina L

International Nuclear Information System (INIS)

Datta, S.K.

1992-01-01

The results of the present experiment on combined treatment with 18 kR X-rays followed by treatment with 0.25, 0.50 and 1.00 per cent aqueous solution of colchicine on white fruit colour variety of T. anguina have been found to be very interesting. The treatments have led to an increase in surviving plants till maturity, reduction in percentage of pollen mother cells with chromosomal aberrations and increase in pollen fertility. Analysis of root tip mitosis has shown that treatment with X-rays produces dicentric bridge and fragment while only polyploid cells were observed after treatment with colchicine. Combined treatment with X-rays and colchicine, produces both chromosomal aberrations and polyploid cells. Simultaneously, it reduces the percentage of cells with chromosomal aberrations and those with polyploid chromosome numbers. Desirable variability in seed number, seed weight and size, seed oil and punicic acid content were observed in both combined and individual treatment. (author). 6 refs., 3 tabs

X-linked adrenoleukodystrophy: clinical and laboratory findings in 15 Brazilian patients

Directory of Open Access Journals (Sweden)

Carmen R. Vargas

2000-06-01

Full Text Available Adrenoleukodystrophy (X-ALD is an X-linked recessively inherited peroxisomal disorder, phenotypically heterogeneous, characterized by progressive white-matter demyelination of the central nervous system and adrenocortical insufficiency. We investigated 15 male X-ALD patients varying in age from 7 to 39, diagnosed among 108 suspected patients referred for investigation. Plasma levels of very long chain fatty acids (VLCFA were measured at our laboratory using gas chromatography (GC. Eleven cases of childhood X-ALD and four cases of adrenomyeloneuropathy (AMN were diagnosed. Adrenal leukodystrophy insufficiency and limb weakness were the most frequent symptoms, appearing in 12, 8 and 6 of the patients, respectively. Physician awareness of X-ALD seems inadequate to judge by age at diagnosis and lengthy interval between the start of symptoms and diagnosis. This is the first published series of Brazilian patients with X-ALD. We determined signs and symptoms relevant for diagnosis, as early identification seems important for treatment outcome. In addition, diagnosis identifies carriers, who could benefit from genetic counselling and prenatal diagnosis.Adrenoleucodistrofia (X-ALD é uma desordem peroxissomal com padrão de herança ligada ao X, fenotipicamente heterogênea, caracterizada por uma progressiva desmielinização da substância branca do sistema nervoso central e por insuficiência adrenal. Foram investigados por nós 15 pacientes do sexo masculino com sinais clínicos sugestivos de X-ALD, com idade entre 7 e 39 anos, diagnosticados entre 108 pacientes encaminhados para investigação por suspeita clínica. Os níveis plasmáticos dos ácidos graxos de cadeia muito longa (VLCFA foram dosados em nosso laboratório através de cromatografia gasosa (GC. Onze (73% casos da forma infantil de X-ALD (ALD e 4 (27% casos de adrenomieloneuropatia (AMN foram diagnosticados. Insuficiência leucodistrofia adrenal e fraqueza muscular foram os sinais mais

[Fragile X syndrome and white matter abnormalities: Case study of two brothers].

Science.gov (United States)

Wallach, E; Bieth, E; Sevely, A; Cances, C

2017-03-01

Fragile X syndrome is the most usual cause of hereditary intellectual deficiency. Typical symptoms combine intellectual deficiency, social anxiety, intense emotional vigilance, and a characteristic facial dysmorphy. This is subsequent to a complete mutation of the FMR1 gene, considering a semidominant transmission linked to the unstable X. The expansion of the CGG triplet greater than 200 units combined with a high methylation pattern lead to a transcriptional silence of the FMR1 gene, and the protein product, the FMRP, is not synthesized. This protein is involved in synaptic plasticity. Brain MRI can show an increased volume of the caudate nucleus and hippocampus, combined with hypoplasia of the cerebellar vermis. Fragile X Associated Tremor Ataxia Syndrome (FXTAS) syndrome is a neurodegenerative disorder occurring in carriers of the premutation in FMR1. Brain MRI shows an increased T2 signal in the middle cerebellar peduncles. This syndrome is linked to a premutation in the FMR1 gene. We report here the case of two brothers presenting a typical fragile X symptomatology. Brain MRI showed hyperintensities of the middle cerebellar peduncles. Such MRI findings support the assumption of a genetic mosaicism. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Analyzer-based x-ray phase-contrast microscopy combining channel-cut and asymmetrically cut crystals

International Nuclear Information System (INIS)

Hoennicke, M. G.; Cusatis, C.

2007-01-01

An analyzer-based x-ray phase-contrast microscopy (ABM) setup combining a standard analyzer-based x-ray phase-contrast imaging (ABI) setup [nondispersive 4-crystal setup (Bonse-Hart setup)] and diffraction by asymmetrically cut crystals is presented here. An attenuation-contrast microscopy setup with conventional x-ray source and asymmetrically cut crystals is first analyzed. Edge-enhanced effects attributed to phase jumps or refraction/total external reflection on the fiber borders were detected. However, the long exposure times and the possibility to achieve high contrast microscopies by using extremely low attenuation-contrast samples motivated us to assemble the ABM setup using a synchrotron source. This setup was found to be useful for low contrast attenuation samples due to the low exposure time, high contrast, and spatial resolution found. Moreover, thanks to the combination with the nondispersive ABI setup, the diffraction-enhanced x-ray imaging algorithm could be applied

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (1)

International Nuclear Information System (INIS)

Shiio, Tsuyoshi; Tsuchiya, Yoshiharu; Ohishi, Kazuo; Yoshihama, Takashi

1988-01-01

Apparent reduction of leukocyte counts was observed in mice irradiated with 1,500 ∼ 3,000 rads of X-ray on the left hind leg. This reduction of leukocyto counts was completely protected by the pre-treatment with lentinan before X-ray irradiation. Suppressive effect of X-ray on the antitumor function of lentinan seems to be weak. When treatment with X-ray irradiation and lentinan was applied for mice bearing solid type sarcoma 180, additive effect was obtained by the combination of lentinan before or after X-ray irradiation. (author)

X-linked agammaglobulinemia - first case with Bruton tyrosine kinase mutation from Pakistan.

Science.gov (United States)

Zaidi, Samreen Kulsom; Qureshi, Sonia; Qamar, Farah Naz

2017-03-01

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency with more than 600 mutations in Bruton tyrosine kinase (Bkt) gene which are responsible for early-onset agammaglobulinemia and repeated infections. Herein we present a case of a 3-year-old boy with history of repeated diarrhoea and an episode of meningoencephalitis with hemiplegia. The workup showed extremely low levels of immunoglobulin with low CD+19 cells. Genetic analysis showed Btk mutation 18 c.1883delCp.T628fs. To the best of our knowledge this is the first report of a case of XLA confirmed by molecular technique from Pakistan.

Drugs + HIV, Learn the Link

Medline Plus

Full Text Available ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to parents, teachers, and the media about the link between drug misuse and HIV. Post on Facebook or Twitter ; add photos to your Flickr , ...

The population genetics of X-autosome synthetic lethals and steriles.

Science.gov (United States)

Lachance, Joseph; Johnson, Norman A; True, John R

2011-11-01

Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

Carrier detection in X-linked retinitis pigmentosa by multipoint DNA analysis. Problems due to genetic heterogeneity

NARCIS (Netherlands)

Bergen, A. A.; Platje, E. J.; Craig, I.; Bakker, E.; Bleeker-Wagemakers, E. M.; van Ommen, G. J.

1991-01-01

DNA diagnosis of X-linked retinitis pigmentosa (XLRP) is hampered by its genetic heterogeneity, while a clinical subdivision is almost impossible to make. So far, diagnostic services have been offered only to those families in which linkage to one RP locus (RP2 or RP3) has been clearly established.

High-speed videography combined with an x-ray image intensifier for dynamic radiography

International Nuclear Information System (INIS)

Bryant, L.E. Jr.

1983-01-01

The Spin Physics SP-2000 high-speed video system can be combined with an x-ray source, a dynamic event having internal (not directly visible) movement and an x-ray image intensifier to perform dynamic radiography. The cesium iodide input fluor and P-20 output fluor of the image intensifier have rapid decay to allow x-ray imaging up to 12,000 pictures per second. Applications of this technique include internal functioning of a compressor, turbulent-water action, and other mechanical actions

Maxillary distraction osteogenesis for treatment of cleft lip and palate in a patient with X-linked agammaglobulinemia.

Science.gov (United States)

Sato, Yutaka; Mishimagi, Takashi; Katsuki, Yuko; Harada, Kiyoshi

2014-07-01

X-linked agammaglobulinemia (XLA) is a congenital immune deficiency disorder caused by abnormal antibody production. It is a rare disease with an estimated frequency of 1 in 379,000 that has X-linked recessive heredity and develops only in males. The clinical problems include bacterial infection such as otitis media, sinusitis, and bronchitis. In recent years it has become possible to diagnose XLA in the early stage and intravenous immunoglobulin replacement therapy has permitted survival to adulthood. However, there have been no reports of oral surgery in patients with XLA. Here, we describe a case in which immunoglobulin replacement therapy given pre- and postoperatively was used to control infection in oral surgery and maxillary distraction osteogenesis performed for improving occlusion and appearance of a cleft lip and palate in a patient with XLA. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome

Energy Technology Data Exchange (ETDEWEB)

Jouet, M.; Kenwick, S. [Univ. of Cambridge (United Kingdom); Moncla, A. [Hopital d`Enfants de la Timone, Marseillas (United Kingdom)] [and others

1995-06-01

The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function. 39 refs., 5 figs., 3 tabs.

Newborn screening for X-linked adrenoleukodystrophy: further evidence high throughput screening is feasible.

Science.gov (United States)

Theda, Christiane; Gibbons, Katy; Defor, Todd E; Donohue, Pamela K; Golden, W Christopher; Kline, Antonie D; Gulamali-Majid, Fizza; Panny, Susan R; Hubbard, Walter C; Jones, Richard O; Liu, Anita K; Moser, Ann B; Raymond, Gerald V

2014-01-01

X-linked adrenoleukodystrophy (ALD) is characterized by adrenal insufficiency and neurologic involvement with onset at variable ages. Plasma very long chain fatty acids are elevated in ALD; even in asymptomatic patients. We demonstrated previously that liquid chromatography tandem mass spectrometry measuring C26:0 lysophosphatidylcholine reliably identifies affected males. We prospectively applied this method to 4689 newborn blood spot samples; no false positives were observed. We show that high throughput neonatal screening for ALD is methodologically feasible. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of the X-linked gene GPR174 in autoimmune Addison's disease.

Science.gov (United States)

Napier, C; Mitchell, A L; Gan, E; Wilson, I; Pearce, S H S

2015-01-01

Autoimmune endocrinopathies demonstrate a profound gender bias, but the reasons for this remain obscure. The 1000 genes on the X chromosome are likely to be implicated in this inherent susceptibility; various theories, including skewed X chromosome inactivation and fetal microchimerism, have been proposed. GPR174 is an Xq21 putative purinergic receptor that is widely expressed in lymphoid tissues. A single-nucleotide polymorphism, rs3827440, encoding Ser162Pro, has recently been associated with Graves' disease in Chinese and Polish populations, suggesting a role of this X chromosome gene in autoimmune disease. We investigated the role of rs3827440 in a UK cohort of patients with autoimmune Addison's disease (AAD). Samples from 286 AAD cases and 288 healthy controls were genotyped using TaqMan single-nucleotide polymorphism genotyping assays (C_25954273_10) on the Applied Biosystems 7900HT Fast real-time PCR system. Using a dominant (present/absent) model, the serine-encoding T allele of rs3827440 was present in 189 of 286 AAD patients (66%) compared with 132 of 288 unaffected controls (46%) [P = .010, odds ratio 1.80 (5%-95% confidence interval 1.22-2.67)]. An allele dosage model found a significant excess of the T allele in AAD patients compared with controls [P = .03, odds ratio 1.34 (5%-95% confidence interval 1.07-1.67)]. We have demonstrated a significant association of this X chromosome-encoded immunoreceptor with AAD for the first time. This X-linked gene could have a more generalized role in autoimmunity pathogenesis: G protein-coupled receptors are promising drugable targets, and further work to elucidate the functional role of GPR174 is now warranted.

Consideration of microstructure evolution and residual stress measurement near severe worked surface using high energy x-ray

International Nuclear Information System (INIS)

Hashimoto, Tadafumi; Mochizuki, Masahito; Shobu, Takahisa

2012-01-01

It is necessary to establish a measurement method that can evaluate accurate stress on the surface. However, the microstructure evolution takes place near the surface due to severe plastic deformation, since structural members have been superpositioned a lot of working processes to complete. As well known, a plane stress can't be assumed on the severe worked surface. Therefore we have been proposed the measurement method that can be measured the in-depth distribution of residual stress components by using high energy X-ray from a synchrotron radiation source. There is the combination of the constant penetration depth method and tri-axial stress analysis. Measurements were performed by diffraction planes for the orientation parameter Γ=0.25 of which elastic constants are nearly equal to the mechanical one. The stress components obtained must be converted to the stress components in real space by using optimization technique, since it corresponds to the weighted average stress components associated with the attenuation of X-ray in materials. The predicted stress components distribution agrees very well with the corrected one which was measured by the conventional removal method. To verify the availability of the proposed method, thermal aging variation of residual stress components on the severe worked surface under elevated temperature was investigated using specimen superpositioned working processes (i.e., welding, machining, peening). It is clarified that the residual stress components increase with thermal aging, using the diffraction planes in hard elastic constants to the bulk. This result suggests that the thermal stability of residual stress has the dependence of the diffraction plane. (author)

Approach to treatment for obstructive jaundice of PTCD guided by combining ultrasound with X-ray scan

International Nuclear Information System (INIS)

Tang Huanliang; Cao Haoqian; Fei Jianguo

2008-01-01

Objective: To investigate the technical and clinical value of PTCD in patients with obstructive jaundice by the guiding of ultrasound combined with X-ray scan. Methods PTCD was performed in 58 patients with obstructive jaundice, with 47 patients malignant diseases and 11 patients benign diseases, guided by combining ultrasound and X-ray scan. 51 patients were punctured to right bile ducts and 7 cases were left bile ducts. Cholangiography was routinely used. Results: Technical success was obtained in all patients. No bleeding and biliary peritonitis were found after procedures. The bilirubin was reduced by 75.4ummol/L one week after operation. Conclusion: The technique of PTCD guided by combining ultrasound with X-ray scan was safe, simple, cost saving and less complications for obstructive jaundice. (authors)

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (2). Combination effect on MM102 syngeneic tumor

Energy Technology Data Exchange (ETDEWEB)

Shiio, Tsuyoshi; Ohishi, Kazuo; Tsuchiya, Yoshiharu; Niitsu, Iwayasu; Hayashibara, Hiromi; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-03-01

C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone. The administration of lentinan before irradiation was effective at the same degree in the group that received lentinan after irradiation. Life prolongation effect was also observed in the group that received lentinan before and after irradiation, and 4 mice among 8 tested mice were survived at 70th day after tumor transplantation.

X-ray analysis of a single aerosol particle with combination of scanning electron microscope and synchrotron radiation X-ray microscope

International Nuclear Information System (INIS)

Toyoda, Masatoshi; Kaibuchi, Kazuki; Nagasono, Mitsuru; Terada, Yasuko; Tanabe, Teruo; Hayakawa, Shinjiro; Kawai, Jun

2004-01-01

We developed a microscope by a combination of synchrotron radiation X-ray fluorescence (SR-XRF) microscope and scanning electron microscope (SEM) with an energy dispersive X-ray spectrometer (EDX). SR-XRF is appropriate to detect trace and micro amount of elements and sensitive to heavy elements in an analyte but it cannot observe the real time image. SEM-EDX can observe the secondary electron image of a single particle in real time and is appropriate to detect lighter elements. This combination microscope can ensure the identification of the XRF spectrum to the SEM image without transferring the sample. For aerosol analysis, it is important to analyze each particle. The present method makes feasible to analyze not only the average elemental composition as the total particles but also elemental composition of each particle, which is dependent on the particle shape and size. The microscope was applied to an individual aerosol particle study. The X-ray spectra were different among the particles, but also different between SR-XRF and SEM-EDX for the same particle, due to the difference in fluorescence yields between X-ray excitation and electron excitation

Skin barrier properties in patients with recessive X-linked ichthyosis

DEFF Research Database (Denmark)

Johansen, J D; Ramsing, D; Vejlsgaard, G

1995-01-01

increased in controls compared to ichthyosis patients, when evaluated by TEWL. When evaluated by erythema index a statistically significant increase in redness was found in controls, but not in ichthyosis patients. Electrical capacitance, reflecting skin hydration, was significantly reduced in RXLI patients......Patients with X-linked recessive ichthyosis (RXLI) were studied as a model of the effect of disturbed epidermal lipid composition on skin barrier function. Thirteen patients with RXLI and 15 age- and sex-matched controls were patch-tested with sodium lauryl sulphate (SLS) 0.5% for 24 h. Basal skin...... properties and skin response to SLS were studied by measurement of transepidermal water loss (TEWL), electrical capacitance and erythema index. No statistically significant difference in basal TEWL was found between the two groups. The skin response to SLS was found to be statistically significantly...

Test-Retest Intervisit Variability of Functional and Structural Parameters in X-Linked Retinoschisis.

Science.gov (United States)

Jeffrey, Brett G; Cukras, Catherine A; Vitale, Susan; Turriff, Amy; Bowles, Kristin; Sieving, Paul A

2014-09-01

To examine the variability of four outcome measures that could be used to address safety and efficacy in therapeutic trials with X-linked juvenile retinoschisis. Seven men with confirmed mutations in the RS1 gene were evaluated over four visits spanning 6 months. Assessments included visual acuity, full-field electroretinograms (ERG), microperimetric macular sensitivity, and retinal thickness measured by optical coherence tomography (OCT). Eyes were separated into Better or Worse Eye groups based on acuity at baseline. Repeatability coefficients were calculated for each parameter and jackknife resampling used to derive 95% confidence intervals (CIs). The threshold for statistically significant change in visual acuity ranged from three to eight letters. For ERG a-wave, an amplitude reduction greater than 56% would be considered significant. For other parameters, variabilities were lower in the Worse Eye group, likely a result of floor effects due to collapse of the schisis pockets and/or retinal atrophy. The criteria for significant change (Better/Worse Eye) for three important parameters were: ERG b/a-wave ratio (0.44/0.23), point wise sensitivity (10.4/7.0 dB), and central retinal thickness (31%/18%). The 95% CI range for visual acuity, ERG, retinal sensitivity, and central retinal thickness relative to baseline are described for this cohort of participants with X-linked juvenile retinoschisis (XLRS). A quantitative understanding of the variability of outcome measures is vital to establishing the safety and efficacy limits for therapeutic trials of XLRS patients.

A STUDY ON RANKING METHOD IN RETRIEVING WEB PAGES BASED ON CONTENT AND LINK ANALYSIS: COMBINATION OF FOURIER DOMAIN SCORING AND PAGERANK SCORING

Directory of Open Access Journals (Sweden)

Diana Purwitasari

2008-01-01

Full Text Available Ranking module is an important component of search process which sorts through relevant pages. Since collection of Web pages has additional information inherent in the hyperlink structure of the Web, it can be represented as link score and then combined with the usual information retrieval techniques of content score. In this paper we report our studies about ranking score of Web pages combined from link analysis, PageRank Scoring, and content analysis, Fourier Domain Scoring. Our experiments use collection of Web pages relate to Statistic subject from Wikipedia with objectives to check correctness and performance evaluation of combination ranking method. Evaluation of PageRank Scoring show that the highest score does not always relate to Statistic. Since the links within Wikipedia articles exists so that users are always one click away from more information on any point that has a link attached, it it possible that unrelated topics to Statistic are most likely frequently mentioned in the collection. While the combination method show link score which is given proportional weight to content score of Web pages does effect the retrieval results.

X-linked gene expression in the Virginia opossum: differences between the paternally derived Gpd and Pgk-A loci

Energy Technology Data Exchange (ETDEWEB)

Samollow, P.B.; Ford, A.L.; VandeBerg, J.L.

1987-01-01

Expression of X-linked glucose-6-phosphate dehydrogenase (G6PD) and phosphoglycerate kinase-A (PGK-A) in the Virginia opossum (Didelphis virginiana) was studied electrophoretically in animals from natural populations and those produced through controlled laboratory crosses. Blood from most of the wild animals exhibited a common single-banded phenotype for both enzymes. Rare variant animals, regardless of sex, exhibited single-banded phenotypes different in mobility from the common mobility class of the respective enzyme. The laboratory crosses confirmed the allelic basis for the common and rare phenotypes. Transmission of PGK-A phenotypes followed the pattern of determinate (nonrandom) inactivation of the paternally derived Pgk-A allele, and transmission of G6PD also was consistent with this pattern. A survey of tissue-specific expression of G6PD phenotypes of heterozygous females revealed, in almost all tissues, three-banded patterns skewed in favor of the allele that was expressed in blood cells. Three-banded patterns were never observed in males or in putatively homozygous females. These patterns suggest simultaneous, but unequal, expression of the maternally and paternally derived Gpd alleles within individual cells. The absence of such partial expression was noted in a parallel survey of females heterozygous at the Pgd-A locus. Thus, it appears that Gpd and Pgk-A are X-linked in D. virginiana and subject to preferential paternal allele inactivation, but that dosage compensation may not be complete for all paternally derived X-linked genes.

Effect of early vitrectomy combined with silicone oil tamponade for severe infectious traumatized endophthalmitis

Directory of Open Access Journals (Sweden)

Xiao Zheng

2013-08-01

Full Text Available AIM: To explore the relations of clinical efficacy and surgical timing of vitrectomy combined with silicone oil tamponade for severe infectious traumatized endophthalmitis.METHODS: Totally 59 patients(59 eyeswith severe infectious traumatized endophthalmitis accepted vitrectomy combined with silicone oil tamponade. Patients were divided into two groups by different surgical timing. Group A accepted operation in 24 hours. Group B accepted operation 24 hours after injury. Retina status during operation, clinical efficacy and best-corrected visual acuity were observed and recorded. RESULTS: The cases of early operation group got lesser retina injury and higher efficacy and better best-corrected visual acuity. CONCLUSION:Vitrectomy combined with silicone oil tamponade is an effective way to cure severe infected traumatized endophthalmitis. Early surgical treatment is the key to achieve better effect.

A new approach to chromosome-wide analysis of X-linked markers identifies new associations in Asian and European case-parent triads of orofacial clefts.

Directory of Open Access Journals (Sweden)

Øivind Skare

Full Text Available GWAS discoveries on the X-chromosome are underrepresented in the literature primarily because the analytical tools that have been applied were originally designed for autosomal markers. Our objective here is to employ a new robust and flexible tool for chromosome-wide analysis of X-linked markers in complex traits. Orofacial clefts are good candidates for such analysis because of the consistently observed excess of females with cleft palate only (CPO and excess of males with cleft lip with or without cleft palate (CL/P.Genotypes for 14,486 X-chromosome SNPs in 1,291 Asian and 1,118 European isolated cleft triads were available from a previously published GWAS. The R-package HAPLIN enables genome-wide-level analyses as well as statistical power simulations for a range of biologic scenarios. We analyzed isolated CL/P and isolated CPO for each ethnicity in HAPLIN, using a sliding-window approach to haplotype analysis and two different statistical models, with and without X-inactivation in females.There was a larger number of associations in the Asian versus the European sample, and similar to previous reports that have analyzed the same GWAS dataset using different methods, we identified associations with EFNB1/PJA1 and DMD. In addition, new associations were detected with several other genes, among which KLHL4, TBX22, CPXCR1 and BCOR were noteworthy because of their roles in clefting syndromes. A few of the associations were only detected by one particular X-inactivation model, whereas a few others were only detected in one sex.We found new support for the involvement of X-linked variants in isolated clefts. The associations were specific for ethnicity, sex and model parameterization, highlighting the need for flexible tools that are capable of detecting and estimating such effects. Further efforts are needed to verify and elucidate the potential roles of EFNB1/PJA1, KLHL4, TBX22, CPXCR1 and BCOR in isolated clefts.

Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy.

Science.gov (United States)

Lawlor, Michael W; Armstrong, Dustin; Viola, Marissa G; Widrick, Jeffrey J; Meng, Hui; Grange, Robert W; Childers, Martin K; Hsu, Cynthia P; O'Callaghan, Michael; Pierson, Christopher R; Buj-Bello, Anna; Beggs, Alan H

2013-04-15

No effective treatment exists for patients with X-linked myotubular myopathy (XLMTM), a fatal congenital muscle disease caused by deficiency of the lipid phosphatase, myotubularin. The Mtm1δ4 and Mtm1 p.R69C mice model severely and moderately symptomatic XLMTM, respectively, due to differences in the degree of myotubularin deficiency. Contractile function of intact extensor digitorum longus (EDL) and soleus muscles from Mtm1δ4 mice, which produce no myotubularin, is markedly impaired. Contractile forces generated by chemically skinned single fiber preparations from Mtm1δ4 muscle were largely preserved, indicating that weakness was largely due to impaired excitation contraction coupling. Mtm1 p.R69C mice, which produce small amounts of myotubularin, showed impaired contractile function only in EDL muscles. Short-term replacement of myotubularin with a prototypical targeted protein replacement agent (3E10Fv-MTM1) in Mtm1δ4 mice improved contractile function and muscle pathology. These promising findings suggest that even low levels of myotubularin protein replacement can improve the muscle weakness and reverse the pathology that characterizes XLMTM.

A link between double-strand break-related repair and V(D)J recombination: the scid mutation

International Nuclear Information System (INIS)

Hendrickson, E.A.; Qin, X.Q.; Bump, E.A.; Schatz, D.G.; Oettinger, M.; Weaver, D.T.

1991-01-01

We show here that mammalian site-specific recombination and DNA-repair pathways share a common factor. The effects of DNA-damaging agents on cell lines derived from mice homozygous for the scid (severe combined immune deficiency) mutation were studied. Surprisingly, all scid cell lines exhibited a profound hypersensitivity to DNA-damaging agents that caused double-strand breaks (x-irradiation and bleomycin) but not to other chemicals that caused single-strand breaks or cross-links. Neutral filter elution assays demonstrated that the x-irradiation hypersensitivity could be correlated with a deficiency in repairing double-strand breaks. These data suggest that the scid gene product is involved in two pathways: DNA repair of random double-strand breaks and the site-specific and lymphoid-restricted variable-(diversity)-joining [V(D)J] DNA rearrangement process. We propose that the scid gene product performs a similar function in both pathways and may be a ubiquitous protein

X-linked recessive panhypopituitarism associated with a regional duplication in Xq25-q26.

Science.gov (United States)

Lagerström-Fermér, M; Sundvall, M; Johnsen, E; Warne, G L; Forrest, S M; Zajac, J D; Rickards, A; Ravine, D; Landegren, U; Pettersson, U

1997-01-01

We present a linkage analysis and a clinical update on a previously reported family with X-linked recessive panhypopituitarism, now in its fourth generation. Affected members exhibit variable degrees of hypopituitarism and mental retardation. The markers DXS737 and DXS1187 in the q25-q26 region of the X chromosome showed evidence for linkage with a peak LOD score (Zmax) of 4.12 at zero recombination fraction (theta(max) = 0). An apparent extra copy of the marker DXS102, observed in the region of the disease gene in affected males and heterozygous carrier females, suggests that a segment including this marker is duplicated. The gene causing this disorder appears to code for a dosage-sensitive protein central to development of the pituitary. Images Figure 2 PMID:9106538

Development and exploitation of the slit method for the characterization of x-ray screen-film combinations

International Nuclear Information System (INIS)

Hoeschen, D.

1987-01-01

For the determination of the modulation transfer function (MTF) of screen-film combinations which are used in medical x-ray diagnostics a measuring method has been developed: the screen-film combination is exposed to x-rays behind a thin slit and the modulation transfer function is calculated from the resulting rather broad slit images on the film. After solving many technical and photographic problems, the slit method provides high precision in the MTF determination. The only objection against this method is the necessary high dose variation which has to be provided by the x-ray machine

Toxicity of various combinations of X-rays, caffeine, and mercury in mouse embryos

Energy Technology Data Exchange (ETDEWEB)

Mueller, W-U. (Universitaetklinikum Essen (Germany, F.R.). Inst. fuer Medizinische Strahlenbiologie)

1989-09-01

Preimplantation mouse embryos in vitro were exposed to various doses of X-rays (0.25-2 Gy) and to different concentrations of two chemicals: caffeine (0.5-2 mM) and mercury (0.5-5 mum). X-irradiation was given first, followed immediately by exposure to the chemicals. The effects of the agents, applied either singly or in combination to two or of three, were studied using morphological, proliferative and cytogenetic endpoints (formation of blastocysts, hatching, trophoblast outgrowth, formation of inner cell mass, cell numbers, micro-nucleus frequency). The term 'enhancement in risk' was used whenever the effects observed after combined exposure (two or three agents) significantly exceeded the sum of the effects due to the component individual agents. The enhancement in risk observed after exposure to the three agents could be explained by the interactions already detected at the level of a combined exposure to only two agents. There was no increase in risk specific for the presence of all three agents. (author).

Mapping X-linked ophthalmic diseases. IV. Provisional assignment of the locus for X-linked congenital cataracts and microcornea (the Nance-Horan syndrome) to Xp22.2-p22.3.

Science.gov (United States)

Lewis, R A; Nussbaum, R L; Stambolian, D

1990-01-01

The Nance-Horan syndrome (NHS) is an infrequent X-linked disorder typified by dense congenital central cataracts, microcornea, anteverted and simplex pinnae, brachymetacarpalia, and numerous dental anomalies. The regional location of the genetic mutation causing NHS is unknown. The authors applied the modern molecular techniques of analysis of restriction fragment length polymorphisms to five multigenerational kindreds in which NHS segregated. Provisional linkage is established to two DNA markers--DXS143 at Xp22.3-p22.2 and DXS43 at Xp22.2. Regional localization of NHS will provide potential antenatal diagnosis in families at risk for the disease and will enhance understanding of the multifaceted genetic defects.

Severe mental deficiency, proportionate dwarfism, and delayed sexual maturation. A distinct inherited syndrome.

Science.gov (United States)

Cantú, J M; Sánchez-Corona, J; García-Cruz, D; Fragoso, R

1980-01-01

Two 46,XY brothers were found to have a previously undescribed syndrome characterized by severe mental deficiency, proportionate dwarfism, and delayed sexual development. A recessive mode of inheritance, either autosomal or X-linked, is assumed.

Apremilast and Narrowband Ultraviolet-B Combination Therapy for Treating Moderate-to-Severe Plaque Psoriasis.

Science.gov (United States)

Bagel, Jerry; Nelson, Elise; Keegan, Brian R

2017-10-01

Combining narrowband UVB (NB-UVB) phototherapy with biologics has been shown to enhance the therapeutic response of plaque psoriasis patients. The objective of this study was to evaluate the effectiveness of apremilast combined with NB-UVB in patients with moderate to severe plaque psoriasis. This was a 12-week, open-label study of 29 patients diagnosed with moderate to severe psoriasis. Patients received apremilast 30 mg twice daily, and increasing doses of NB-UVB (310-312 nm) 3 times per week for 12 weeks. Twenty-two of 29 patients (76%) completed the 12-week apremilast and NB-UVB combination therapy; 73% (16 of 22 completers) achieved a PASI 75 response at week 12. Mean scores for PASI, VAS pain, VAS itch, DLQI, and PGA improved by 77%, 77%, 69%, 70%, and 67%, respectively, at week 12. The most commonly reported adverse events (AEs) were mild and moderate first-degree burns related to NB-UVB (n=11 [38%] patients). A second-degree NB-UVB burn was reported (likely due to an underlying photosensitivity) and was considered a serious AE. The combination of apremilast with NB-UVB was effective for the treatment of moderate to severe plaque psoriasis, without any unexpected safety signals. Apremilast combined with NB-UVB provided a high treatment response in patients with moderate to severe plaque psoriasis, and may be an option for patients to enhance a patient's initial therapeutic response. J Drugs Dermatol. 2017;16(10):957-962..

X-ray studies on electrochemical systems. Synchrotron methods for energy materials

Energy Technology Data Exchange (ETDEWEB)

Braun, Artur [Empa. Eidgenoessische Materialpruefungs- und Forschungsanstalt, Duebendorf (Switzerland)

2017-07-01

This book is your graduate level entrance into battery, fuel cell and solar cell research at synchrotron X-ray sources. Materials scientists find numerous examples for the combination of electrochemical experiments with simple and with highly complex X-ray scattering and spectroscopy methods. Physicists and chemists can link applied electrochemistry with fundamental concepts of condensed matter physics, physical chemistry and surface science.

Generation of induced pluripotent stem cells from a patient with X-linked juvenile retinoschisis

Directory of Open Access Journals (Sweden)

Chi-Hsien Peng

2018-05-01

Full Text Available X-linked juvenile retinoschisis (XLRS is a hereditary retinal dystrophy manifested as splitting of anatomical layers of retina. In this report, we generated a patient-specific induced pluripotent stem cell (iPSC line, TVGH-iPSC-013-05, from the peripheral blood mononuclear cells of a male patient with XLRS by using the Sendai-virus delivery system. We believe that XLRS patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.

X-ray targeting puncture collagenase chemonucleolysis combined with injection of medical ozone for the treatment of lumbar disc herniation

International Nuclear Information System (INIS)

Yao Lin; Zhu Genfa

2011-01-01

Objective: To evaluate the clinical value of X-ray target puncture collagenase chemonucleolysis combined with injection of medical ozone for lumbar disc herniation. Methods: One thousand and sixty-two cases of lumbar disc herniation accepted collagenase chemonucleolysis combined with injection of medical ozone targeted by X-ray. The therapeutic effects after operation were analyzed. Results: Of all the 1062 cases, the effective rate of X-ray target puncture collagenase chemonucleolysis combined with injection of medical ozone was 95.3% at 3 months, 92.3% at 12 months, and 91.2% at 24 months after operation. Conclusion: X-ray target puncture collagenase chemonucleolysis combined with injection of medical ozone is a simple and safe method for the lumbar disc herniation. It also had fewer adverse reactions and better therapeutic effects. (authors)

Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

DEFF Research Database (Denmark)

Patterson, Emily J.; Wilk, Melissa; Langlo, Christopher S.

2016-01-01

encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants......PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations...... to clarify the link between color vision deficiency and cone dysfunction.  METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone...

ZNF674: A New Kruppel-Associated Box-Containing Zinc-Finger Gene Involved in Nonsyndromic X-Linked Mental Retardation

NARCIS (Netherlands)

Lugtenberg, D.; Yntema, H.G.; Banning, M.J.G.; Oudakker, A.R.; Firth, H.; Willatt, L.; Raynaud, M.; Kleefstra, T.; Fryns, J.P.; Ropers, H.H.; Chelly, J.; Moraine, C.; Gecz, J.; Reeuwijk, J. van; Nabuurs, S.B.; Vries, L.B.A. de; Hamel, B.C.J.; Brouwer, A.P.M. de; Bokhoven, J.H.L.M. van

2006-01-01

Array-based comparative genomic hybridization has proven to be successful in the identification of genetic defects in disorders involving mental retardation. Here, we studied a patient with learning disabilities, retinal dystrophy, and short stature. The family history was suggestive of an X-linked

Submicroscopic interstitial deletion of the X chromosome explains a complex genetic syndrome dominated by Norrie disease.

Science.gov (United States)

Gal, A; Wieringa, B; Smeets, D F; Bleeker-Wagemakers, L; Ropers, H H

1986-01-01

Norrie disease (ND), an X-linked recessive disorder, is characterized by congenital blindness followed by bulbar atrophy. We have examined a three-generation family in which ND is part of a complex X-linked syndrome with severe mental retardation, hypogonadism, growth disturbances, and increased susceptibility to infections as additional features. This syndrome is apparently due to an interstitial deletion, as evidenced by the failure of the L1.28 DNA probe (DXS7 locus, Xp11.3) to detect complementary DNA sequences on the defective X chromosome of an affected male and of several obligatory heterozygotes. Attempts to further define this deletion with other DNA probes from the proximal short arm of the X chromosome or by prometaphase chromosome analysis were unsuccessful.

An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males

Directory of Open Access Journals (Sweden)

Chung Ren-Hua

2011-11-01

Full Text Available Abstract Background Autism spectrum disorder (ASD is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD. Methods We analyzed genome-wide association study (GWAS data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case-control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set. Results One SNP, rs17321050, in the transducin β-like 1X-linked (TBL1X gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (P value = 4.86 × 10-6 and joint analysis (P value = 4.53 × 10-6 in males. The SNP was also close to the replication threshold of 0.0025 in the discovery data set (P = 5.89 × 10-3 and passed the replication threshold in the validation data set (P = 2.56 × 10-4. Two other SNPs in the same gene in linkage disequilibrium with rs17321050 also showed significance close to the chromosome-wide threshold in the meta-analysis. Conclusions TBL1X is in the Wnt signaling pathway, which has previously been implicated as having a role in autism. Deletions in the Xp22.2 to Xp22.3 region containing TBL1X and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, based on meta-analysis, joint analysis and replication analysis, suggest that TBL1X may play a role in ASD risk.

System analysis regarding NO{sub x} reduction with combined SNCR/SCR; Systemstudie avseende kombinerad NO{sub x}-reducering med SNCR/SCR

Energy Technology Data Exchange (ETDEWEB)

Niemann, Therese; Henningsson, Claes [S.E.P. Scandinavian Energy Project AB, Stockholm (Sweden); Andersson, Christer [Vattenfall Utveckling AB, Stockholm (Sweden)

2000-06-01

Systems with combined SNCR/SCR on biomass fired CFB:s have been focused on lately since they are regarded as very load flexible. Furthermore, synergy effects between the two parts are supposed to result in better performance for the combined system than for the two systems separately. The aim of this study is to investigate whether the combined SNCR/SCR matches the outlined expectations above. The plant chosen for the measurements was Brista Kraft AB. This particular plant is equipped with a CFB boiler of 122 MW{sub th}, which in turn is equipped with the deNO{sub x} system mentioned above. The measurements are made by a 'concentration gradient measurement system', developed by Vattenfall. Consequently, the study indicates that it is very useful to add a catalyst to the SNCR system, both from an environmental- and an economical point of view. However, since the full scale data for the SCR alone is missing, the results for SCR compared with combined SNCR/SCR is harder to decide. Simulations indicate that both systems produces the same emission levels, although, the SCR system may be a bit more cost effective in the long run. The synergy effect between the systems in combination is obvious. Predominantly because the NO{sub x} reduction efficiency in the SNCR zone can be increased (in this case about 10-12%) since a higher amount of ammonia can be accepted downstream of the SNCR zone. Combined systems will achieve a comparable good load independence. The reduction in the SNCR will decrease at lower loads, simultaneously as the reduction in the SCR increases. Thus, the total reduction efficiency will almost be independent of the load. In the project investigations have been made to figure out if two points injection in SNCR give more or less mol distribution of NH{sub 3}/NO quota over the catalyst crosses sectional area. The measurements indicates that two point injection may cause a more uneven distribution of stoichiometries. However, the results seems to

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (2)

International Nuclear Information System (INIS)

Shiio, Tsuyoshi; Ohishi, Kazuo; Tsuchiya, Yoshiharu; Niitsu, Iwayasu; Hayashibara, Hiromi; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-01-01

C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone. The administration of lentinan before irradiation was effective at the same degree in the group that received lentinan after irradiation. Life prolongation effect was also observed in the group that received lentinan before and after irradiation, and 4 mice among 8 tested mice were survived at 70th day after tumor transplantation. (author)

X-linked lissencephaly with abnormal genitalia associated with renal phosphate wasting.

Science.gov (United States)

Hahn, A; Gross, C; Uyanik, G; Hehr, U; Hügens-Penzel, M; Alzen, G; Neubauer, B A

2004-06-01

X-linked lissencephaly with abnormal genitalia (XLAG) is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene. We report on the clinical data of a boy with a 1-bp deletion (790 delC) resulting in a frame shift in the ARX gene and prolonged survival until age 18 months. Similar to other patients, the boy showed postnatal microcephaly, hypothalamic dysfunction, intractable neonatal seizures, and chronic diarrhoea. In addition, he suffered from exocrine pancreatic insufficiency and renal phosphate wasting became apparent from age 5 months, both of which have not been described previously in XLAG. This allows us to speculate that the phenotype of XLAG is more complex than hitherto known and may include renal phosphate wasting which might not have been observed in other patients due to early death.

Inverse dynamic analysis of general n-link robot manipulators

International Nuclear Information System (INIS)

Yih, T.C.; Wang, T.Y.; Burks, B.L.; Babcock, S.M.

1996-01-01

In this paper, a generalized matrix approach is derived to analyze the dynamic forces and moments (torques) required by the joint actuators. This method is general enough to solve the problems of any n-link open-chain robot manipulators with joint combinations of R(revolute), P(prismatic), and S(spherical). On the other hand, the proposed matrix solution is applicable to both nonredundant and redundant robotic systems. The matrix notation is formulated based on the Newton-Euler equations under the condition of quasi-static equilibrium. The 4 x 4 homogeneous cylindrical coordinates-Bryant angles (C-B) notation is applied to model the robotic systems. Displacements, velocities, and accelerations of each joint and link center of gravity (CG) are calculated through kinematic analysis. The resultant external forces and moments exerted on the CG of each link are considered as known inputs. Subsequently, a 6n x 6n displacement coefficient matrix and a 6n x 1 external force/moment vector can be established. At last, the joint forces and moments needed for the joint actuators to control the robotic system are determined through matrix inversion. Numerical examples will be illustrated for the nonredundant industrial robots: Bendix AA/CNC (RRP/RRR) and Unimate 2000 spherical (SP/RRR) robots; and the redundant light duty utility arm (LDUA), modified LDUA, and tank waste retrieval manipulator system

Three-year experience with combined treatment with alendronate and alfacalcidol in Japanese patients with severe bone loss and osteoporotic fracture

Directory of Open Access Journals (Sweden)

Iwamoto J

2011-06-01

Full Text Available Jun Iwamoto1, Yoshihiro Sato2, Mitsuyoshi Uzawa3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, Japan; 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanPurpose: Combined treatment with alendronate and alfacalcidol is more useful to increase bone mineral density (BMD than alendronate or alfacalcidol alone. A retrospective study was conducted to investigate the 3-year outcome of combined treatment with alendronate and alfacalcidol in patients with severe bone loss (BMD ≤ 50% of the young adult mean and osteoporotic fracture.Methods: Thirty-four patients (six men and 28 postmenopausal women with primary or secondary osteoporosis who had been treated with alendronate and alfacalcidol for more than 3 years were analyzed. The lumbar spine or total hip BMD and bone turnover markers were monitored, and the incidence of osteoporotic fractures was assessed.Results: The urinary level of cross-linked N-terminal telopeptides of type I collagen and serum level of alkaline phosphatase significantly decreased (-42.5% at 3 months and -18.9% at 3 years, and the lumbar spine BMD, but not the total hip BMD, significantly increased (14.8% at 3 years, compared with the baseline values. However, the incidence of vertebral and nonvertebral fractures was 26.5% and 2.9%, respectively, suggesting a high incidence of vertebral fractures.Conclusion: The results of the present study suggest that combined treatment with alendronate and alfacalcidol may be useful to reduce bone turnover and increase the lumbar spine BMD in patients with severe bone loss and osteoporotic fracture. However, its efficacy against vertebral fractures appears not to be sufficient. Thus, anabolic agents such as teriparatide should be taken into consideration as first-line drugs in patients with severe osteoporosis.Keywords: osteoporosis

Review Recent progress in identification and characterization of loci associated with sex-linked congenital cataract.

Science.gov (United States)

Zhang, D D; Du, J Z; Topolewski, J; Wang, X M

2016-07-29

Congenital cataract is a common cause of blindness in children; however, its pathogenesis remains unclear. Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract. The current genetic models of congenital cataract include autosomal dominant, autosomal recessive, and sex-linked inheritance. Sex-linked congenital cataract could be inherited through the X or Y chromosome. Congenital cataract is a symptom associated with several X-linked disorders, including Nance-Horan syndrome, Lowe syndrome, Conradi-Hünermann-Happle syndrome, oculo-facio-cardio-dental syndrome, and Alport syndrome. On the other hand, the mechanism and characteristics of Y-linked congenital cataract remains to be identified. Despite its rarity, sex-linked congenital cataract has been known to seriously affect the quality of life of patients. In this review, we present our current understanding of the genes and loci associated with sex-linked congenital cataract. This could help identify novel approaches for the prevention, early diagnosis, and comprehensive disease treatment.

Subacute combined spinal cord degeneration and pancytopenia secondary to severe vitamin B12 deficiency

Directory of Open Access Journals (Sweden)

José Luis Cabrerizo-García

Full Text Available CONTEXT: Decreased vitamin B12 concentration does not usually result in clinical or hematological abnormalities. Subacute combined spinal cord degeneration and pancytopenia are two serious and rarely displayed consequences that appear in severe deficits. CASE REPORT: We present the case of a patient with subacute combined spinal cord degeneration and pancytopenia secondary to severe and sustained vitamin B12 deficiency. Such cases are rare nowadays and have potentially fatal consequences. CONCLUSIONS: Vitamin B12 deficiency should be taken into consideration in the differential diagnosis in cases of blood disorders or severe neurological symptoms. Early diagnosis and treatment can avoid irreversible consequences.

Effect of combined treatment of x-rays and ACNU on rat glioma cells in monolayer and multicellular spheroids

International Nuclear Information System (INIS)

Sugiyama, Satoru; Mori, Teruaki; Suzuki, Jiro; Sasaki, Takehito

1985-01-01

Spheroids of rat glioma clone-6 cells having a central necrosis were used to determine the effect of combined treatment of x-rays and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), where the optimum time intervals and doses in the combination were analyzed. The treatment with ACNU 2 to 6 hours prior to x-ray irradiation was most effective for cells in both monolayers and in spheroids. The dose survival curves with x-ray irradiation indicated that the hypoxic cell fraction in spheroids disappeared with a prior treatment by ACNU. The enhancement ratio in spheroids was thus larger for larger x-ray doses, and was always larger than that in monolayer cells. The survival curves versus concentration of ACNU indicated that the enhancement ratio in spheroids was more than 1.2 in all concentrations with the combined x-ray irradiation, and exceeded that in monolayer cells with a surviving fraction of less than 0.4. (author)

Disseminated BCG infection in a patient with severe combined immunodeficiency

International Nuclear Information System (INIS)

Han, Tae Il; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo

2000-01-01

Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy

Disseminated BCG infection in a patient with severe combined immunodeficiency

Energy Technology Data Exchange (ETDEWEB)

Han, Tae Il [Eulji University School of Medicine, Taejon (Korea, Republic of); Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2000-06-01

Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy.

Treatment of Severe Maxillary Hypoplasia With Combined Orthodontics and Distraction Osteogenesis.

Science.gov (United States)

Lucchese, Alessandra; Albertini, Paolo; Asperio, Paolo; Manuelli, Maurizio; Gastaldi, Giorgio

2018-01-05

Distraction osteogenesis (DO) is a technique that allows the generation of new bone in a gap between 2 vascularized bone surfaces in response to the application of graduated tensile stress across the bone gap.Distraction osteogenesis has become a routine treatment of choice to correct skeletal deformities and severe bone defects in the craniofacial complex over the past decade. Distraction osteogenesis has been successfully chosen in lengthening the maxilla and the mandible; in the maxilla and recently in the mandible, the jawbones have been distracted and widened transversely to relieve severe anterior dental crowding and transverse discrepancies between the dental arches.Distraction osteogenesis for maxillary advancement started in 1993 and is now widely used, especially in patients with skeletal Class III malocclusion caused by maxillary hypoplasia.The aim of this study was to present the efficiency of combined orthodontic and DO in the severe maxillary hypoplasia.A 35-year-old Italian man presented to our clinical practice with the chief complaint of esthetic and functionally problems because of skeletal Class III malocclusion with anterior crossbite.Considering that the severity of the skeletal discrepancy is remarkable but compensated by the DO potential, the combined orthodontic and DO treatment was considered adequate, like less invasive and equally effective.It was obtained a good alignment with the upper and lower arch dental alveolar maxillary advancement that allowed to correct the sagittal relationships.The patient was satisfied for the treatment results and had considerable improvement in his self-esteem.

Preparation of nanostructured La{sub 0.7}Ca{sub 0.3−x}Ba{sub x}MnO{sub 3} ceramics by a combined sol–gel and spark plasma sintering route and resulting magnetocaloric properties

Energy Technology Data Exchange (ETDEWEB)

Ayadi, F.; Regaieg, Y. [Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 15 rue J.-A. de Baïf, 75205 Paris Cedex 13 (France); Faculté des Sciences de Sfax, Université de Sfax, LPM, B.P 1171, 3000 Sfax (Tunisia); Cheikhrouhou-Koubaa, W.; Koubaa, M.; Cheikhrouhou, A. [Faculté des Sciences de Sfax, Université de Sfax, LPM, B.P 1171, 3000 Sfax (Tunisia); Lecoq, H.; Nowak, S.; Ammar, S. [Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 15 rue J.-A. de Baïf, 75205 Paris Cedex 13 (France); Sicard, L., E-mail: lorette.sicard@univ-paris-diderot.fr [Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 15 rue J.-A. de Baïf, 75205 Paris Cedex 13 (France)

2015-05-01

This work proposes an original, easy to achieve and inexpensive route to synthesize manganite ceramics for magnetic refrigeration, combining sol–gel chemistry to Spark Plasma Sintering (SPS). The target La{sub 0.7}Ca{sub 0.3−x}Ba{sub x}MnO{sub 3} (x=0, 0.1, 0.2) compounds are obtained as single phases which crystallize in the orthorhombic structure (Pnma space group). SPS allows a quick sintering at a relatively low temperature (700 °C in this work) compared to the conventional solid state method (≥1100 °C), leading to densified ultrafine grained pellets (85% of compactness). Magnetic studies show that Ba substitution does not affect significantly the relative cooling power (RCP) of these manganites, while it increases their Curie temperature (T{sub C}) by several tens of degrees. Typically, RCP values ranging between 267 and 270 J/kg (for a magnetic field change of 5 T) and T{sub C} between 205 and 245 K were measured when x was increased from 0 to 0.2, respectively. These results combined to the fact that the synthesis route is economically advantageous makes the obtained ceramics interesting as active refrigerants for magnetic refrigeration technology below room temperature. - Highlights: • Nanostructured La{sub 0.7}Ca{sub 0.3−x}Ba{sub x}MnO{sub 3} ceramics were obtained as single phase. • An original and low cost method was developed combining sol–gel chemistry and SPS. • The method can be extended to prepare most dense nanostructured oxides. • Our ceramics have higher RCP than those obtained by the solid state method. • The optimum temperature of the magnetocaloric effect is tunable with Ba content.

On the wide-energy-range tuning of x-ray photoemission electron microscope optics for the observation of the photoelectrons excited by several keV x-rays

International Nuclear Information System (INIS)

Yasufuku, H.; Yoshikawa, H.; Kimura, M.; Vlaicu, A.M.; Kato, M.; Kudo, M.; Fujikata, J.; Fukushima, S.

2006-01-01

We have newly developed an x-ray photoemission electron microscope (XPEEM) which uses both soft x-rays and hard x-rays at the undulator beam line BL15XU in the synchrotron radiation (SR) facility SPring-8 to observe various practical materials. In combination with an energy analyzer and high brilliant x-ray source, the detection of high kinetic energy inner-shell photoelectrons is essential for revealing the chemical properties of specimen subsurfaces or buried interfaces, owing to long inelastic mean free path of the high kinetic energy photoelectrons. The most significant result in our design is the new combined electric and magnetic field objective lens in which the magnetic field penetrates up to the sample surface. This allows the measurement with high spatial resolution of both low intensity images of inner-shell photoelectrons with high kinetic energy and high intensity images of secondary electrons. By using the sample bias scan method, we can easily change the focus condition of the objective lens in order to allow the energy filtered imaging with photoelectrons having the kinetic energy in a wide range (1-10 000 eV). By the combination of high brilliant SR x-rays, the new objective lens, and sample bias method, our XPEEM can successfully obtain the microarea x-ray photoelectron spectra and energy filtered XPEEM images of inner-shell photoelectrons, such as Si 1s, without any surface cleaning procedure. The energy filtered XPEEM image using photoelectrons from deep inner shells, Si 1s, was obtained for the first time

Severe combined hyperlipidaemia and retinal lipid infiltration in a patient with Type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Rae Derek

2006-12-01

Full Text Available Abstract Severe combined hyperlipidaemia has occasionally been associated with infiltration of tissues in addition to arteries and the skin. We report a woman with Type 2 diabetes mellitus (DM and severe combined hyperlipidaemia who developed retinal lipid infiltration, resulting in blindness. A 61-year-old woman with a 15-year history of Type 2 DM was admitted following a two-week history of progressive visual loss. Examination identified lipid infiltration into the retina. Phenotypically she had severe combined hyperlipidaemia with elevated IDL cholesterol and a broad beta band on lipoprotein electrophoresis, raising the possibility of familial dysbetalipoproteinaemia. However, gene sequencing analysis indicated that the patient was homozygous for the E3/E3 allele of the ApoE gene with no mutations detected in either the coding region or intron-exon boundaries. Her lipid profile improved following dietary therapy and gemfibrozil treatment, but this had little effect on either her fundal appearances or her visual acuity. Type 2 DM plays a vital role both in allowing expression of severe combined hyperlipoproteinaemia, in addition to serving as a risk factor for complications such as tissue infiltration.

Misdiagnosis of X-linked retinitis pigmentosa in a choroideremia patient with heavily pigmented fundi.

Science.gov (United States)

Nanda, A; Salvetti, A P; Martinez-Fernandez de la Camara, C; MacLaren, R E

2018-06-01

Inherited retinal diseases are thought to be the leading cause of sight loss in the working age population. Mutations found in the RPGR and CHM genes cause retinitis pigmentosa (RP) and choroideremia, respectively. In the first instance, an X-linked family history of visual field loss commonly raises the suspicion of one of these two genes. In choroideremia, the classic description of a white fundal reflex secondary to the widespread chorioretinal degeneration was made over a hundred years ago in Caucasians. But, it is not so obvious in heavily pigmented fundi. Hence, the clinical diagnosis of CHM in non-Caucasian patients may be challenging in the first stages of the disease. Here we report a case of a Southeast Asian gentleman who has a family history of X-linked retinal degeneration and was found to have a confirmed in-frame deletion of 12 DNA nucleotides in exon 15 of the RPGR gene. Later in life, however, his fundal appearance showed unusual areas of circular pigment hypertrophy and clumping. He was therefore tested for carrying a disease-causing mutation in the CHM gene and a null mutation was found. Since gene therapy trials are ongoing for both of these conditions, it has now become critically important to establish the correct genetic diagnosis in order to recruit suitable candidates. Moreover, this case demonstrates the necessity to remain vigilant in the interpretation of genetic results which are inconsistent with clinical features.

Impact of gold nanoparticles combined to X-Ray irradiation on bacteria

International Nuclear Information System (INIS)

Simon-Deckers, A.; Gouget, B.; Carriere, M.; Brun, E.; Sicard-Roselli, C.

2008-01-01

Recent increase of multi drug-resistant bacteria represents a crucial issue of public health. As innovative approaches are required to face that problem, those emerging from nano-technology are of great interest. In that context we propose the possibility to use gold nano-particles combined with ionising radiation to destroy pathogenic bacteria. For that, we investigated the potential X-Rays enhanced reduction of bacterial cell viability, following nanoparticle exposure, on a bacterial model, Escherichia coli. Our first concern was to confirm the absence of toxicity of the colloidal solution used. Then, we developed an X-Ray irradiation system and showed that gold nanoparticles increased the efficiency of ionising radiation to induce bacteria cell death. (authors)

A novel AVPR2 gene mutation of X-linked congenital nephrogenic diabetes insipidus in an Asian pedigree.

Science.gov (United States)

Guo, Wei-Hong; Li, Qiang; Wei, Hong-Yan; Lu, Hong-Yan; Qu, Hui-Qi; Zhu, Mei

2016-10-01

Polyuria and polydipsia are the characteristics of congenital nephrogenic diabetes insipidus (CNDI). Approximately 90% of all patients with CNDI have X-linked hereditary disease, which is due to a mutation of the arginine vasopressin receptor 2 ( AVPR2) gene. This case report describes a 54-year-old male with polyuria and polydipsia and several male members of his pedigree who had the same symptoms. The proband was diagnosed with diabetes insipidus using a water-deprivation and arginine vasopressin stimulation test. Genomic DNA from the patient and his family members was extracted and the AVPR2 gene was sequenced. A novel missense mutation of a cytosine to guanine transition at position 972 (c.972C > G) was found, which resulted in the substitution of isoleucine for methionine at amino acid position 324 (p.I324M) in the seventh transmembrane domain of the protein. The proband's mother and daughter were heterozygous for this mutation. The novel mutation of the AVPR2 gene further broadens the phenotypic spectrum of the AVPR2 gene.

A THEORETICAL FRAMEWORK FOR COMBINING TECHNIQUES THAT PROBE THE LINK BETWEEN GALAXIES AND DARK MATTER

International Nuclear Information System (INIS)

Leauthaud, Alexie; Tinker, Jeremy; Behroozi, Peter S.; Busha, Michael T.; Wechsler, Risa H.

2011-01-01

We develop a theoretical framework that combines measurements of galaxy-galaxy lensing, galaxy clustering, and the galaxy stellar mass function in a self-consistent manner. While considerable effort has been invested in exploring each of these probes individually, attempts to combine them are still in their infancy. These combinations have the potential to elucidate the galaxy-dark matter connection and the galaxy formation physics responsible for it, as well as to constrain cosmological parameters and to test the nature of gravity. In this paper, we focus on a theoretical model that describes the galaxy-dark matter connection based on standard halo occupation distribution techniques. Several key modifications enable us to extract additional parameters that determine the stellar-to-halo mass relation and to simultaneously fit data from multiple probes while allowing for independent binning schemes for each probe. We construct mock catalogs from numerical simulations to investigate the effects of sample variance and covariance for each probe. Finally, we analyze how trends in each of the three observables impact the derived parameters of the model. In particular, we investigate various features of the observed galaxy stellar mass function (low-mass slope, 'plateau', knee, and high-mass cutoff) and show how each feature is related to the underlying relationship between stellar and halo mass. We demonstrate that the observed 'plateau' feature in the stellar mass function at M * ∼ 2 x 10 10 M sun is due to the transition that occurs in the stellar-to-halo mass relation at M h ∼ 10 12 M sun from a low-mass power-law regime to a sub-exponential function at higher stellar mass.

Stress release and defect occurrence in V1-xFe x films upon hydrogen loading: H-induced superabundant vacancies, movement and creation of dislocations

KAUST Repository

Gemma, Ryota; Dobroň, Patrik; Čí žek, Jakub; Pundt, Astrid A.

2014-01-01

Hydrogen-induced elastic/plastic deformation was studied in V 1-xFex (x = 0.02-0.08) films with thicknesses between 10 and 400 nm and prepared at different temperatures. The combination of several in situ techniques such as X-ray diffraction, acoustic emission, electromotive force and substrate curvature techniques allows sensitive studies of defects generated in these thin films. As well as conventional out-of-plane linear elastic film expansion and in-plane compressive stress increase during hydrogen absorption, the investigations uncovered new details: as soon as hydrogen predominately solved in interstitial lattice sites, discrete stress relaxation (DSR) events were detected, after which the film continued to behave in a linear elastic manner. DSRs were interpreted by uncorrelated movement of pre-existing dislocations. Particularly in the case of films deposited at higher temperatures, in-plane tensile stress was found at very small H concentrations of less than 0.005 H/V. Upon further H uptake, this turned into compressive stress. However, this stress increase differed from theoretical predictions. This behavior is explained by the generation of superabundant vacancies. Dislocation emission and plastic deformation are linked to the formation of the hydride phase in the V1-xFex films. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Stress release and defect occurrence in V1-xFe x films upon hydrogen loading: H-induced superabundant vacancies, movement and creation of dislocations

KAUST Repository

Gemma, Ryota

2014-04-01

Hydrogen-induced elastic/plastic deformation was studied in V 1-xFex (x = 0.02-0.08) films with thicknesses between 10 and 400 nm and prepared at different temperatures. The combination of several in situ techniques such as X-ray diffraction, acoustic emission, electromotive force and substrate curvature techniques allows sensitive studies of defects generated in these thin films. As well as conventional out-of-plane linear elastic film expansion and in-plane compressive stress increase during hydrogen absorption, the investigations uncovered new details: as soon as hydrogen predominately solved in interstitial lattice sites, discrete stress relaxation (DSR) events were detected, after which the film continued to behave in a linear elastic manner. DSRs were interpreted by uncorrelated movement of pre-existing dislocations. Particularly in the case of films deposited at higher temperatures, in-plane tensile stress was found at very small H concentrations of less than 0.005 H/V. Upon further H uptake, this turned into compressive stress. However, this stress increase differed from theoretical predictions. This behavior is explained by the generation of superabundant vacancies. Dislocation emission and plastic deformation are linked to the formation of the hydride phase in the V1-xFex films. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Impact of Conventional Medical Therapy on Bone Mineral Density and Bone Turnover in Adult Patients with X-Linked Hypophosphatemia

DEFF Research Database (Denmark)

Shanbhogue, Vikram Vinod; Hansen, Stinus; Jørgensen, Niklas Rye

2018-01-01

X-linked hypophosphatemia (XLH) is a rare, inheritable disorder manifesting as rickets in children and osteomalacia in adults. While conventional medical treatment with oral phosphate and alfacalcidol is recommended in childhood, it is undecided whether adults should continue therapy. The aim...

X linked progressive cone dystrophy. Localisation of the gene locus to Xp21-p11.1 by linkage analysis

NARCIS (Netherlands)

Meire, F. M.; Bergen, A. A.; de Rouck, A.; Leys, M.; Delleman, J. W.

1994-01-01

Six affected males, three female carriers, and two possible carriers were evaluated from a three generation pedigree with X linked progressive cone dystrophy. The affected males presented with progressive decrease of visual acuity, impairment of colour vision, and deterioration of electroretinogram,

Asthma Severity in patients initiating controller monotherapy versus combination therapy.

Science.gov (United States)

Diette, Gregory B; Fuhlbrigge, Anne L; Allen-Ramey, Felicia; Hopper, April; Sajjan, Shiva G; Markson, Leona E

2011-04-01

Asthma treatment guidelines recommend medications based on the level of asthma control. To evaluate differences in asthma control between patients who initiated asthma controller monotherapy versus combination therapy. Children (5-16 years; n = 488) and adults (17-80 years; n = 530) with asthma and no controller therapy in the prior 6 months were included. Telephone surveys were conducted within 5 days of filling a new asthma controller prescription with either the caregiver of children or the adult patient. Demographics, asthma control before therapy, and asthma-related resource use were assessed for patients initiating monotherapy (filling one asthma controller prescription) and combination therapy (filling more than one controller medication or a fixed-dose combination). Mean pediatric age was 10 years; 53% were male. Mean adult age was 47 years; 25% were male. There were no significant differences in asthma control score between patients receiving monotherapy and combination therapy. Children on combination therapy did not have more nighttime awakening or short-acting β-agonist use but were more likely to have been hospitalized due to asthma attack (p = .05) and have more unscheduled (p = .0374) and scheduled (p = .009) physician visits. Adults on combination therapy were more likely to have been hospitalized due to asthma attack (p asthma (p asthma control scores in the 4 weeks before index medication suggests that asthma severity during a treatment-free period did not differ significantly for patients initiating controller monotherapy versus combination therapy. From these findings, it appears that although physicians may not focus on asthma control when choosing the intensity of initial controller therapy, the intensity of health-care encounters may be an influence.

Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency?

DEFF Research Database (Denmark)

Orngreen, M.C.; Schelhaas, H.J.; Jeppesen, T.D.

2008-01-01

OBJECTIVE: It is unclear to what extent muscle phosphorylase b kinase (PHK) deficiency is associated with exercise-related symptoms and impaired muscle metabolism, because 1) only four patients have been characterized at the molecular level, 2) reported symptoms have been nonspecific, and 3......) lactate responses to ischemic handgrip exercise have been normal. METHODS: We studied a 50-year-old man with X-linked PHK deficiency using ischemic forearm and cycle ergometry exercise tests to define the derangement of muscle metabolism. We compared our findings with those in patients with Mc...... in healthy subjects. Constant workload elicited a second wind in all patients with McArdle disease, but not in the patient with PHK deficiency. IV glucose administration appeared to improve exercise tolerance in the patient with PHK deficiency, but not to the same extent as in the patients with Mc...

Identification of novel missense mutations in the Norrie disease gene associated with one X-linked and four sporadic cases of familial exudative vitreoretinopathy.

Science.gov (United States)

Shastry, B S; Hejtmancik, J F; Trese, M T

1997-01-01

X-linked Familial Exudative Vitreoretinopathy (XLFEVR) is a hereditary eye disorder that affects both the retina and the vitreous body. It is characterized by an abnormal vascularization of the peripheral retina. It has been previously shown by linkage and candidate gene analysis that XLFEVR and Norrie disease are allelic. In this report we describe four novel mutations (R41K, H42R, K58N, and Y120C) in the Norrie disease gene associated with one X-linked and four sporadic cases of FEVR. One mutation (H42R) was found to be segregating with the disease in three generations (X-linked family), and the others are sporadic. These sequence alterations changed the encoded amino acids in the Norrie disease protein and were not found in 17 unaffected family members or in 36 randomly selected normal individuals. This study provides additional evidence that mutations in the same gene can result in FEVR and Norrie disease. It also demonstrates that it may be beneficial for clinical diagnosis to screen for mutations in the Norrie disease gene in sporadic FEVR cases.

Modulation of rotavirus severe gastroenteritis by the combination of probiotics and prebiotics.

Science.gov (United States)

Gonzalez-Ochoa, Guadalupe; Flores-Mendoza, Lilian K; Icedo-Garcia, Ramona; Gomez-Flores, Ricardo; Tamez-Guerra, Patricia

2017-09-01

Annual mortality rates due to infectious diarrhea are about 2.2 million; children are the most vulnerable age group to severe gastroenteritis, representing group A rotaviruses as the main cause of disease. One of the main factors of rotavirus pathogenesis is the NSP4 protein, which has been characterized as a viral toxin involved in triggering several cellular responses leading to diarrhea. Furthermore, the rotavirus protein NSP1 has been associated with interferon production inhibition by inducing the degradation of interferon regulatory factors IRF3, IRF5, and IRF7. On the other hand, probiotics such as Bifidobacterium and Lactobacillus species in combination with prebiotics such as inulin, HMO, scGOS, lcFOS have been associated with improved generalized antiviral response and anti-rotavirus effect by the reduction of rotavirus infectivity and viral shedding, decreased expression of NSP4 and increased levels of specific anti-rotavirus IgAs. Moreover, these probiotics and prebiotics have been related to shorter duration and severity of rotavirus diarrhea, to the prevention of infection and reduced incidence of reinfections. In this review we will discuss in detail about the rotavirus pathogenesis and immunity, and how probiotics such as Lactobacillus and Bifidobacterium species in combination with prebiotics have been associated with the prevention or modulation of rotavirus severe gastroenteritis.

A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy.

Science.gov (United States)

Chen, Z Y; Battinelli, E M; Fielder, A; Bundey, S; Sims, K; Breakefield, X O; Craig, I W

1993-10-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina. Both autosomal dominant (adFEVR) and X-linked (XLFEVR) forms have been described, but the biochemical defect(s) underlying the symptoms are unknown. Molecular analysis of the Norrie gene locus (NDP) in a four generation FEVR family (shown previously to exhibit linkage to the X-chromosome markers DXS228 and MAOA (Xp11.4-p11.3)) reveals a missense mutation in the highly conserved region of the NDP gene, which caused a neutral amino acid substitution (Leu124Phe), was detected in all of the affected males, but not in the unaffected family members, nor in normal controls. The observations suggest that phenotypes of both XLFEVR and Norrie disease can result from mutations in the same gene.

Sequence-dependent toxicity and small bowel mucosal injury in neonatal mice treated with low doses of 5-azacytidine and X-irradiation at the late organogenesis stage

International Nuclear Information System (INIS)

Schmahl, W.

1983-01-01

A combined treatment of pregnant mice on day 12 of gestation with both azacytidine and X-irradiation in low doses induces sequence-dependent histological effects. These effects, in turn, induce different symptomatic signs if evaluated either prenatally or neonatally. In the azacytidine treatment/X-irradiation sequence the malformations of the fetal forebrain are predominant. Consequently, these dams show a high incidence in the stillbirth rate. Conversely, the X-irradiation/azacytidine treatment schedule leads only to a mild brain hypoplasia, and does not cause an increased stillbirth rate. In these offspring, however, a severe impairment of small bowel epithelial proliferation capacity was found. This is linked to an outstanding neonatal mortality within 48 h after birth. The pathogenesis of these sequence-dependent effects can be attributed to a selective vulnerability of cells in different stages of the generation cycle. This comprises a high degree of cytolethality affecting the S/G 2 -stage cells in azacytidine/X-irradiation treatment and the G 1 /S-stage cells in the reverse combinations (Schmahl 1979). The present observations show the validity of a teratological assay in providing a detailed analysis of the cell kinetic responses after combined noxious influences. (orig.)

Helically linked mirror arrangement

International Nuclear Information System (INIS)

Ranjan, P.

1986-08-01

A scheme is described for helical linking of mirror sections, which endeavors to combine the better features of toroidal and mirror devices by eliminating the longitudinal loss of mirror machines, having moderately high average β and steady state operation. This scheme is aimed at a device, with closed magnetic surfaces having rotational transform for equilibrium, one or more axisymmetric straight sections for reduced radial loss, a simple geometrical axis for the links and an overall positive magnetic well depth for stability. We start by describing several other attempts at linking of mirror sections, made both in the past and the present. Then a description of our helically linked mirror scheme is given. This example has three identical straight sections connected by three sections having helical geometric axes. A theoretical analysis of the magnetic field and single-particle orbits in them leads to the conclusion that most of the passing particles would be confined in the device and they would have orbits independent of pitch angle under certain conditions. Numerical results are presented, which agree well with the theoretical results as far as passing particle orbits are concerned

Combined model of 9x9 playfair and RSA for securing confidential ...

African Journals Online (AJOL)

Combined model of 9x9 playfair and RSA for securing confidential information. Y.B. Zakariyau, L.J. Muhammad, A.M. Usman, A Garba. Abstract. No Abstract. Keywords: Cryptography, RSA, Playfair Cipher, Public and Secret Key. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL ...

Disseminated bacillus calmette guerin disease in a twin infant with severe combined immunodeficiency disease

Directory of Open Access Journals (Sweden)

Hema Mittal

2014-01-01

Full Text Available Fatal-disseminated Bacillus Calmette Guerin (BCG disease is well known in infants with severe combined immunodeficiency after BCG vaccination. We report a 7 month male infant delivered as a product of in vitro fertilization and twin gestation that presented with fever, cough and multiple nodular skin lesions. A biopsy of skin lesions revealed the presence of acid fast bacilli. Mycobacterium bovis infection was confirmed by polymerase chain reaction (PCR and molecular studies. Immunological profile confirmed the diagnosis of severe combined immunodeficiency. Only few reports of similar case exist in the literature.

Effects of oxygen stoichiometry on the scaling behaviors of YBa{sub 2}Cu{sub 3}O{sub x} grain boundary weak-links

Energy Technology Data Exchange (ETDEWEB)

Wu, K.H.; Fu, C.M.; Jeng, W.J. [National Chiao-Tung Univ., Taiwan (China)] [and others

1994-12-31

The effects of oxygen stoichiometry on the transport properties of the pulsed laser deposited YBa{sub 2}Cu{sub 3}O{sub x} bicrystalline grain boundary weak-link junctions were studied. It is found that not only the cross boundary resistive transition foot structure can be manipulated repeatedly with oxygen annealling processes but the junction behaviors are also altered in accordance. In the fully oxygenated state i.e. with x=7.0 in YBa{sub 2}Cu{sub 3}O{sub x} stoichiometry, the junction critical current exhibits a power of 2 scaling behavior with temperature. In contrast, when annealed in the conditions of oxygen-deficient state (e.g. with x=6.9 in YBa{sub 2}Cu{sub 3}O{sub x} stoichiometry) the junction critical current switches to a linear temperature dependence behavior. The results are tentatively attributed to the modification of the structure in the boundary area upon oxygen annealing, which, in turn, will affect the effective dimension of the geometrically constrained weak-link bridges. The detailed discussion on the responsible physical mechanisms as well as the implications of the present results on device applications will be given.

The first de novo mutation of the connexin 32 gene associated with X linked Charcot-Marie-Tooth disease

NARCIS (Netherlands)

Meggouh, F.; Benomar, A.; Rouger, H.; Tardieu, S.; Birouk, N.; Tassin, J.; Barhoumi, C.; Yahyaoui, M.; Chkili, T.; Brice, A.; LeGuern, E.

1998-01-01

X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary motor and sensory neuropathy caused by mutations in the connexin 32 gene (Cx32). Using the SSCP technique and direct sequencing of PCR amplified genomic DNA fragments of the Cx32 gene from a Moroccan patient and her relatives, we identified

X-Linked Recessive Form of Nephrogenic Diabetes Insipidus in A 7-Year-Old Boy

Directory of Open Access Journals (Sweden)

Janchevska A.

2014-12-01

Full Text Available Nephrogenic diabetes insipidus (NDI is caused by the inability of renal collecting duct cells to respond to arginine vasopressin (AVP/antidiuretic hormone (ADH. We present the case of a 7-year-old boy with a history of excretion of large amounts of dilute urine and polydipsia since infancy. The boy had several vomiting episodes with mild dehydration during the first 3 years of life. There was no evidence of headaches, dizziness or visual problems. He drinks between 2 and 3 L/day and has 24-hour diuresis of 2 liters, now. He has prepubertal appearance with appropriate weight [+0.85 standard deviation score (SDS] and height (+0.15 SDS for his age. His intelligence was also normal. The water deprivation test showed low urine osmolality after 8 hours of dehydration. After desmopressin administration, urine osmolality remained low. Serum osmolality was in the normal range for sex and age before and after desmopressin administration. This indicated a nephrogenic form of diabetes insipidus. Molecular analyses revealed a P286L [p.Pro(CCC286Leu(CTC] mutation in the AVPR2 gene, that was inherited from his mother. This patient is the first case with genetically confirmed X-linked inherited form of NDI in the Republic of Macedonia. Molecular analysis confirmed the clinical diagnosis and enabled genetic advice for this family.

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (1). Fundamental studies

Energy Technology Data Exchange (ETDEWEB)

Shiio, Tsuyoshi; Tsuchiya, Yoshiharu; Ohishi, Kazuo; Yoshihama, Takashi

1988-02-01

Apparent reduction of leukocyte counts was observed in mice irradiated with 1,500 approx. 3,000 rads of X-ray on the left hind leg. This reduction of leukocyto counts was completely protected by the pre-treatment with lentinan before X-ray irradiation. Suppressive effect of X-ray on the antitumor function of lentinan seems to be weak. When treatment with X-ray irradiation and lentinan was applied for mice bearing solid type sarcoma 180, additive effect was obtained by the combination of lentinan before or after X-ray irradiation.

The ultraluminous X-ray sources NGC 1313 X-1 and X-2: A broadband study with NuSTAR and XMM-Newton

Energy Technology Data Exchange (ETDEWEB)

Bachetti, Matteo; Barret, Didier; Webb, Natalie A. [Université de Toulouse, UPS-OMP, IRAP, Toulouse (France); Rana, Vikram; Walton, Dominic J.; Harrison, Fiona A.; Fürst, Felix; Grefenstette, Brian W.; Madsen, Kristin K. [Cahill Center for Astronomy and Astrophysics, Caltech, Pasadena, CA 91125 (United States); Boggs, Steven E.; Craig, William W. [Space Sciences Laboratory, University of California, Berkeley, CA 94720 (United States); Christensen, Finn E. [DTU Space, National Space Institute, Technical University of Denmark, Elektrovej 327, DK-2800 Lyngby (Denmark); Fabian, Andrew C. [Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA (United Kingdom); Hailey, Charles J. [Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027 (United States); Hornschemeier, Ann; Ptak, Andrew F.; Zhang, William W. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Miller, Jon M. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109-1042 (United States); Stern, Daniel, E-mail: matteo.bachetti@irap.omp.eu [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States)

2013-12-01

We present the results of NuSTAR and XMM-Newton observations of the two ultraluminous X-ray sources: NGC 1313 X-1 and X-2. The combined spectral bandpass of the two satellites enables us to produce the first spectrum of X-1 between 0.3 and 30 keV, while X-2 is not significantly detected by NuSTAR above 10 keV. The NuSTAR data demonstrate that X-1 has a clear cutoff above 10 keV, whose presence was only marginally detectable with previous X-ray observations. This cutoff rules out the interpretation of X-1 as a black hole in a standard low/hard state, and it is deeper than predicted for the downturn of a broadened iron line in a reflection-dominated regime. The cutoff differs from the prediction of a single-temperature Comptonization model. Further, a cold disk-like blackbody component at ∼0.3 keV is required by the data, confirming previous measurements by XMM-Newton only. We observe a spectral transition in X-2, from a state with high luminosity and strong variability to a lower-luminosity state with no detectable variability, and we link this behavior to a transition from a super-Eddington to a sub-Eddington regime.

Cyclophosphamide/x-ray: combined mode preparation for transplantation therapy

International Nuclear Information System (INIS)

Meredith, R.; Okunewick, J.; Shadduck, R.; Raikow, R.; Brozovich, B.; Seeman, P.

1979-01-01

Use of total body irradiation (TBI) and/or chemotherapy as a preparation for marrow transplantation in the treatment of leukemia has been only moderately successful in the clinic. Although cyclophosphamide (CY) has shown promise as a marrow ablative agent, leukemia relapses are often found, and optimal therapeutic protocols have not been established. Our transplantation therapy studies of murine leukemia with parental recipients and hybrid donors provide an excellent model for research aimed at improved survival of human transplant patients. Utilizing a murine leukemia induced by a virus, various doses of CY in combination with sub-lethal irradiation were compared to determine the optimal pretreatment for transplantation therapy. Both normal and leukemic mice were engrafted with virus resistant, histocompatible marrow following these preparations, then monitored for survival and long term effects. Leukemic mice were also evaluated for pluripotent as well as myeloid committed stem cells as a measure of the effectiveness of the treatment in elimination of leukemic cells. Leukemic groups were also compared for the percentage and time of leukemia relapse. All CY/X-ray combinations were more effective in elimination of stem cell populations than supralethal TBI alone. However, the best survival was obtained with lethal TBI alone or low dose CY in combination with 550 R

Structure/Psychophysical Relationships in X-Linked Retinoschisis.

Science.gov (United States)

Bennett, Lea D; Wang, Yi-Zhong; Klein, Martin; Pennesi, Mark E; Jayasundera, Thiran; Birch, David G

2016-02-01

To compare structural properties from spectral-domain optical coherence tomography (SDOCT) and psychophysical measures from a subset of patients enrolled in a larger multicenter natural history study of X-linked retinoschisis (XLRS). A subset of males (n = 24) participating in a larger natural history study of XLRS underwent high-resolution SDOCT. Total retina (TR) thickness and outer segment (OS) thickness were measured manually. Shape discrimination hyperacuity (SDH) and contour integration perimetry (CIP) were performed on an iPad with the myVisionTrack application. Sensitivity was measured with fundus-guided perimetry (4-2 threshold testing strategy; 10-2 grid, spot size 3, 68 points). Correlation was determined with Pearson's r correlation. Values are presented as the mean ± SD. Mean macular OS thickness was less in XLRS patients (17.2 ± 8.1 μm) than in controls (37.1 ± 5.7 μm; P weak correlation with TR thickness (R(2) = 0.22, P = 0.0158). The XLRS subjects had a logMAR best corrected visual acuity (BCVA) of 0.5 ± 0.3 that was associated with OS (R(2) = 0.79, P < 0.0001) but not TR thickness (R(2) = 0.01, P = 0.6166). Shape DH and CIP inner ring correlated with OS (R(2) = 0.33, P = 0.0085 and R(2) = 0.47, P = 0.0001, respectively) but not TR thickness (R(2) = 0.0004, P = 0.93; R(2) = 0.0043, P = 0.75, respectively). When considered from a single visit, OS thickness within the macula is more closely associated with macular function than TR thickness within the macula in patients with XLRS.

Process Monitoring by combining several signal-analysis results using fuzzy logic

International Nuclear Information System (INIS)

Schoonwelle, H.; Van der Hagen, T.H.J.J.; Hoogenboom, J.E.

1996-01-01

In order to improve reliability in detecting anomalies in nuclear power plant performance, a method is presented which is based on acquiring various characteristics of signal data using autoregressive, wavelet and fractal-analysis techniques. These characteristics are combined using a decision making approach based on fuzzy logic. This approach is able to detect and distinguish several system states

Successful nonsibling bone marrow transplantation in severe combined immunodeficiency

DEFF Research Database (Denmark)

Ramsøe, K; Skinhøj, P; Andersen, V

1978-01-01

Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA......-A antigen but was HLA-Dw2 homozygous like the patient; his lymphocytes showed a slight response to the patient's cells in mixed lymphocyte culture (MLC). At the age of 2 1/2 months and again at 5 months, she was given a bone marrow transplant from the father. During the entire course the patient had...

X-linked hypophosphatemia. A phenotype in search of a cause.

Science.gov (United States)

Tenenhouse, H S; Scriver, C R

1992-05-01

XLH is an important disease, it is the subject of several classic articles in the medical sciences (Scriver et al., 1991), and it has been an important stimulus to study renal hypophosphatemias and how they are involved in rickets and osteomalacia (Scriver, 1974; Scriver and Tenenhouse, 1991). Renal transport is the major determinant of phosphate homeostasis in mammals and it is unlikely that this important biochemical parameter would have been left by evolution to a single renal transport system. Together physiologists and geneticists found that the mammalian kidney has several gene products dedicated to phosphate transport. That has implications for biochemists in search of a membrane protein to clone and explain XLH, for example. Let us suppose the transporter affected in XLH is cloned. Will it be the product of the XLH (or Hyp or Gy) locus? One will not know until the transporter gene is mapped. There is no question of the X-chromosome locus product being protein kinase C for example, since it maps to autosomes. But where does one start in the search for the X-chromosome locus? With the elusive putative diffusible factor or with the transporter, or perhaps with an enzyme in vitamin D hormone metabolism? Which goes to say that it is necessary to know the phenotype to arrive at the right locus. Or is it? Sufficient physical mapping of region Xp22.31-p21.3 will eventually lead to positional cloning of the Hyp gene. What will it be?(ABSTRACT TRUNCATED AT 250 WORDS)

A novel missense mutation of NDP in a Chinese family with X-linked familial exudative vitreoretinopathy.

Science.gov (United States)

Liu, Hong Yan; Huang, Jia; Wang, Rui Li; Wang, Yue; Guo, Liang Jie; Li, Tao; Wu, Dong; Wang, Hong Dan; Guo, Qian Nan; Dong, Dao Quan

2016-11-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. In this report, we describe a novel missense mutation of the Norrie disease gene (NDP) in a Chinese family with X-linked FEVR. Ophthalmologic evaluation was performed on four male patients and seven unaffected individuals after informed consent was obtained. Venous blood was collected from the 11 members of this family, and genomic DNA was extracted using standard methods. The coding exons 2 and 3 and their corresponding exon-intron junctions of NDP were amplified by polymerase chain reaction and then subjected to direct DNA sequencing. A novel missense mutation (c.310A>C) in exon 3, leading to a lysine-to-glutamine substitution at position 104 (p.Lys104Gln), was identified in all four patients with X-linked FEVR. Three unaffected female individuals (III2, IV3, and IV11) were found to be carriers of the mutation. This mutation was not detected in other unaffected individuals. The mutation c.310A>C (p.Lys104Gln) in exon 3 of NDP is associated with FEVR in the studied family. This result further enriches the mutation spectrum of FEVR. Copyright © 2016. Published by Elsevier Taiwan LLC.

A novel missense mutation of NDP in a Chinese family with X-linked familial exudative vitreoretinopathy

Directory of Open Access Journals (Sweden)

Hong Yan Liu

2016-11-01

Full Text Available Familial exudative vitreoretinopathy (FEVR is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. In this report, we describe a novel missense mutation of the Norrie disease gene (NDP in a Chinese family with X-linked FEVR. Ophthalmologic evaluation was performed on four male patients and seven unaffected individuals after informed consent was obtained. Venous blood was collected from the 11 members of this family, and genomic DNA was extracted using standard methods. The coding exons 2 and 3 and their corresponding exon–intron junctions of NDP were amplified by polymerase chain reaction and then subjected to direct DNA sequencing. A novel missense mutation (c.310A>C in exon 3, leading to a lysine-to-glutamine substitution at position 104 (p.Lys104Gln, was identified in all four patients with X-linked FEVR. Three unaffected female individuals (III2, IV3, and IV11 were found to be carriers of the mutation. This mutation was not detected in other unaffected individuals. The mutation c.310A>C (p.Lys104Gln in exon 3 of NDP is associated with FEVR in the studied family. This result further enriches the mutation spectrum of FEVR.

X-ray spectra of PG quasars. I. The continuum from X-rays to infrared

International Nuclear Information System (INIS)

Elvis, M.; Green, R.F.; Bechtold, J.; Schmidt, M.; Neugebauer, G.; Kitt Peak National Observatory, Tucson, AZ; Steward Observatory, Tucson, AZ; Palomar Observatory, Pasadena, CA)

1986-01-01

Einstein IPC X-ray spectra for a sample of eight optically selected quasars from the Palomar Bright Quasar survey are presented. The quasars have a mean power law energy slope which in five individual cases is inconsistent with the value found in hard X-ray selection criterion rather than luminosity, redshift, or U-B color. New IUE and optical continuum spectra and infrared photometry are presented for these quasars. The data are combined into log vf(v) and log v distributions which support the decomposition of the overall quasar spectrum into a power law plus a superposed optical-UV big bump which may be due to an accretion disk. At least six of the quasars have vf(v)s which are roughly constant between their infrared and X-ray power laws, suggesting a strong link between the two regions. 104 references

Association of CHRDL1 mutations and variants with X-linked megalocornea, Neuhäuser syndrome and central corneal thickness

DEFF Research Database (Denmark)

Davidson, Alice E; Cheong, Sek-Shir; Hysi, Pirro G

2014-01-01

We describe novel CHRDL1 mutations in ten families with X-linked megalocornea (MGC1). Our mutation-positive cohort enabled us to establish ultrasonography as a reliable clinical diagnostic tool to distinguish between MGC1 and primary congenital glaucoma (PCG). Megalocornea is also a feature of Ne...

Graphene-like monolayer InSe–X: several promising half-metallic nanosheets in spintronics

Science.gov (United States)

Liu, Jun; Kang, Wei; Zhou, Ting-Yan; Ma, Chong-Geng

2018-04-01

Several half-metallic graphene-like nanosheets, namely halogen atom adsorbed InSe–X (X  =  F, Cl, Br and I) nanosheets, are predicted by first-principles calculations. Then, their structural, electric and magnetic properties are studied in detail. The calculated negative adsorption energies of these InSe–X nanosheets ensure that they attain stable adsorption structures, which suggests that they may be prepared experimentally. The pristine InSe monolayer is a typical semi-conductor, whereas it is interesting that the X ion (X  =  F, Cl, Br and I) adsorbed InSe–X nanosheets are electronically conductive. They can be promising and good candidates for applications of half-metallic 2D materials. The calculated magnetic moments of these nanosheets are close to 1.0 µ B. In the InSe–F nanosheet, there are sp2 hybridized orbitals due to the crystal field effect, and its electroconductibility, half-metallicity and magnetic moments originate from the In and Se ions, not the F ion. However, in InSe–X (X  =  Cl, Br and I) nanosheets, there are sp3 hybridized orbitals, and their electroconductibility, half-metallicity and magnetic moments originate mainly from X ions, together partially with the In and Se ions.

X-Linked Dyskeratosis Congenita Is Predominantly Caused by Missense Mutations in the DKC1 Gene

OpenAIRE

Knight, S.W.; Heiss, N.S.; Vulliamy, T.J.; Greschner, S.; Stavrides, G.; Pai, G.S.; Lestringant, G.; Varma, N.; Mason, P.J.; Dokal, I.; Poustka, A.

1999-01-01

Dyskeratosis congenita is a rare inherited bone marrow-failure syndrome characterized by abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. More than 80% of patients develop bone-marrow failure, and this is the major cause of premature death. The X-linked form of the disease (MIM 305000) has been shown to be caused by mutations in the DKC1 gene. The gene encodes a 514-amino-acid protein, dyskerin, that is homologous to Saccharomyces cerevisiae Cbf5p and rat Nap57 proteins. B...

Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1

Science.gov (United States)

Jensen, Lars R; Chen, Wei; Moser, Bettina; Lipkowitz, Bettina; Schroeder, Christopher; Musante, Luciana; Tzschach, Andreas; Kalscheuer, Vera M; Meloni, Ilaria; Raynaud, Martine; van Esch, Hilde; Chelly, Jamel; de Brouwer, Arjan P M; Hackett, Anna; van der Haar, Sigrun; Henn, Wolfram; Gecz, Jozef; Riess, Olaf; Bonin, Michael; Reinhardt, Richard; Ropers, Hans-Hilger; Kuss, Andreas W

2011-01-01

X-linked intellectual disability (XLID), also known as X-linked mental retardation, is a highly genetically heterogeneous condition for which mutations in >90 different genes have been identified. In this study, we used a custom-made sequencing array based on the Affymetrix 50k platform for mutation screening in 17 known XLID genes in patients from 135 families and found eight single-nucleotide changes that were absent in controls. For four mutations affecting ATRX (p.1761M>T), PQBP1 (p.155R>X) and SLC6A8 (p.390P>L and p.477S>L), we provide evidence for a functional involvement of these changes in the aetiology of intellectual disability. PMID:21267006

Texture, residual stress and structural analysis of thin films using a combined X-ray analysis

International Nuclear Information System (INIS)

Lutterotti, L.; Chateigner, D.; Ferrari, S.; Ricote, J.

2004-01-01

Advanced thin films for today's industrial and research needs require highly specialized methodologies for a successful quantitative characterization. In particular, in the case of multilayer and/or unknown phases a global approach is necessary to obtain some or all the required information. A full approach has been developed integrating novel texture and residual stress methodologies with the Rietveld method (Acta Cryst. 22 (1967) 151) (for crystal structure analysis) and it has been coupled with the reflectivity analysis. The complete analysis can be done at once and offers several benefits: the thicknesses obtained from reflectivity can be used to correct the diffraction spectra, the phase analysis help to identify the layers and to determine the electron density profile for reflectivity; quantitative texture is needed for quantitative phase and residual stress analyses; crystal structure determination benefits of the previous. To achieve this result, it was necessary to develop some new methods, especially for texture and residual stresses. So it was possible to integrate them in the Rietveld, full profile fitting of the patterns. The measurement of these spectra required a special reflectometer/diffractometer that combines a thin parallel beam (for reflectivity) and a texture/stress goniometer with a curved large position sensitive detector. This new diffraction/reflectivity X-ray machine has been used to test the combined approach. Several spectra and the reflectivity patterns have been collected at different tilting angles and processed at once by the special software incorporating the aforementioned methodologies. Some analysis examples will be given to show the possibilities offered by the method

Medical management of severe local radiation injury after acute X-ray exposure

International Nuclear Information System (INIS)

Bushmanov, A.; Nadezhina, N.; Kretov, A.

2008-01-01

Medical management during acute period in a case of severe local radiation injury after acute X-ray exposure includes 3 stages. During the fist stage patient got conservative treatment according to the common pathogenetic mechanisms of LRI (dis aggregating therapy, stimulation of regeneration, dis intoxication therapy, antibiotic therapy, pain relief therapy, Local anti-burn therapy-specific non-adhesive bandage with antiseptic and anti-burn medicaments); estimation of severity, deepness and area of injury by clinical picture and dates of instrumental methods of examining; defining necessity and volume of surgical treatment; preparing arrangements for surgical treatment. This stage ends with forming of demarcation line of a very hard severity of a Local Radiation Injure. The second stage includes necrectomy of the area of a very hard severity with microsurgical plastic by re vascularized flap and auto dermoplastic. The third stage - adaptation of re vascularized flap and total epithelization of injured area. (author)

A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease.

LENUS (Irish Health Repository)

Murphy, Sinéad M

2011-03-01

X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene which codes for connexin 32 (CX32). CX32 has three tissue-specific promoters, P1 which is specific for liver and pancreas, P1a specific for liver, oocytes and embryonic stem cells, and P2 which is nerve-specific. Over 300 mutations have been described in GJB1, spread throughout the coding region. We describe two families with X-linked inheritance and a phenotype consistent with CMT1X who did not have mutations in the GJB1 coding region. The non-coding region of GJB1 was sequenced and an upstream exon-splicing variant found at approximately - 373G>A which segregated with the disease in both families and was not present in controls. This substitution is located at the last base of the nerve-specific 5\\'UTR and thus may disrupt splicing of the nerve-specific transcript. Online consensus splice-site programs predict a reduced score for the mutant sequence vs. the normal sequence. It is likely that other mutations within the GJB1 non-coding regions account for the CMT1X families who do not have coding region mutations.

Fluorine-18-fluorodeoxyglucose positron emission tomography (PET) brain imaging patterns in patients with suspected X-linked dystonia parkinsonism (study in progress)

International Nuclear Information System (INIS)

Santiago, J.F.Y.; Fugoso, L.; Evidente, V.G.H.

2004-01-01

Objective: X-linked dystonia-parkinsonism (XDP or Lubag) is an adult-onset dystonia syndrome that afflicts mostly Filipino men from the island of Panay, Philippines.It starts focally and becomes generalized or multifocal after the first five years. Parkinsonism is commonly encountered as the initial symptom before the onset of dystonia. Patients may manifest a wide spectrum of movement disorders, including myoclonus, chorea, akathisia, ballism and myorhythmia. Diagnosis is based on the clinical presentation, and the establishment of an x-linked recessive pattern of inheritance and maternal roots from the Panay Islands. Neuroimaging in advanced cases have demonstrated caudate and putaminal atrophy. Previous studies using PET have shown selective reduction in normalized striatal glucose metabolism. The purpose of this study is to describe the FDG distribution using PET imaging in Filipino patients with suspected or confirmed Lubag in various stages of their disease in order to determine if FDG-PET can be used in the initial diagnosis and staging of the disease. Methods and results: All patients presenting to the Movement Disorders Center of St. Lukes Medical Center with dystonia and Parkinsonism symptoms with X-linked recessive inheritance pattern and maternal roots traceable to the Panay Islands were sent for a Brain FDG PET Scan. Seven male patients with various movement disorders (dysarthria, face dystonia, Parkinsonism, hemibalismus, involuntary movements and rest tremors) with duration of symptoms from 1 to 5 years underwent a PET scan. All patients had non visualized bilateral putamen, four had hypometabolic caudate nuclei, one had intense (hypermetabolic) caudate nuclei. CT scan and MRI did not show any findings which may explain the movement disorder symptoms. More patients are being collected and gene typing is planned for some patients. Conclusions: This small series of patients demonstrate that patients with the phenotypic characteristics of X-linked

New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism

Energy Technology Data Exchange (ETDEWEB)

Yanase, Toshihiko; Takayanagi, Ryoichi; Oba, Koichi [Kyushu Univ., Fukuoka (Japan)] [and others

1996-02-01

Congenital adrenal hypoplasia, an X-linked disorder, is characterized by primary adrenal insufficiency and frequent association with hypogonadotropic hypogonadism. The X-chromosome gene DAX-1 has been most recently identified and shown to be responsible for this disorder. We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism by using PCR amplification of genomic DNA and its complete exonic sequencing. In a family containing several affected individuals, the proband male patient had a stop codon (TGA) in place of tryptophan (TGG) at amino acid position 171. As expected, his mother was a heterozygous carrier for the mutation, whereas his father and unaffected brother did not carry this mutation. In another male patient with noncontributory family history, sequencing revealed a 1-bp (T) deletion at amino acid position 280, leading to a frame shift and, subsequently a premature stop codon at amino acid position 371. The presence of this mutation in the patients` genome was further confirmed by digestion of genomic PCR product with MspI created by this mutation. Family studies using MspI digestion of genomic PCR products revealed that neither parent of this individual carried the mutation. These results clearly indicate that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene. 31 refs., 4 figs., 2 tabs.

Neonatal screening for severe combined immunodeficiency in Brazil

Directory of Open Access Journals (Sweden)

Marilia Pyles Patto Kanegae

2016-07-01

Full Text Available Objective: To apply, in Brazil, the T-cell receptor excision circles (TRECs quantification technique using real-time polymerase chain reaction in newborn screening for severe combined immunodeficiency and assess the feasibility of implementing it on a large scale in Brazil. Methods: 8715 newborn blood samples were collected on filter paper and, after DNA elution, TRECs were quantified by real-time polymerase chain reaction. The cutoff value to determine whether a sample was abnormal was determined by ROC curve analysis, using SSPS. Results: The concentration of TRECs in 8,682 samples ranged from 2 to 2,181 TRECs/μL of blood, with mean and median of 324 and 259 TRECs/μL, respectively. Forty-nine (0.56% samples were below the cutoff (30 TRECs/μL and were reanalyzed. Four (0.05% samples had abnormal results (between 16 and 29 TRECs/μL. Samples from patients previously identified as having severe combined immunodeficiency or DiGeorge syndrome were used to validate the assay and all of them showed TRECs below the cutoff. Preterm infants had lower levels of TRECs than full-term neonates. The ROC curve showed a cutoff of 26 TRECs/μL, with 100% sensitivity for detecting severe combined immunodeficiency. Using this value, retest and referral rates were 0.43% (37 samples and 0.03% (3 samples, respectively. Conclusion: The technique is reliable and can be applied on a large scale after the training of technical teams throughout Brazil. Resumo: Objetivo: aplicar no Brasil a técnica de quantificação de T-cell Receptor Excision Circles (TRECs por polymerase chain reaction em tempo real para triagem neonatal de imunodeficiência combinada grave (SCID e avaliar se é possível realizá-la em larga escala em nosso país. Métodos: foram coletadas 8.715 amostras de sangue de recém-nascidos em papel filtro e, após eluição do DNA, os TRECs foram quantificados por polymerase chain reaction em tempo real. O valor de corte para determinar se uma

X-chromosome inactivation in development and cancer.

Science.gov (United States)

Chaligné, Ronan; Heard, Edith

2014-08-01

X-chromosome inactivation represents an epigenetics paradigm and a powerful model system of facultative heterochromatin formation triggered by a non-coding RNA, Xist, during development. Once established, the inactive state of the Xi is highly stable in somatic cells, thanks to a combination of chromatin associated proteins, DNA methylation and nuclear organization. However, sporadic reactivation of X-linked genes has been reported during ageing and in transformed cells and disappearance of the Barr body is frequently observed in cancer cells. In this review we summarise current knowledge on the epigenetic changes that accompany X inactivation and discuss the extent to which the inactive X chromosome may be epigenetically or genetically perturbed in breast cancer. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Drugs + HIV, Learn the Link

Medline Plus

Full Text Available ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to parents, teachers, and the media ...

Effect of combined treatments of pepleomycin with x-ray in cultured cells of a mouse squamous cell carcinoma

International Nuclear Information System (INIS)

Yokota, Masahiko; Wakamatsu, Yoshiko; Sairenji, Eiko; Ohara, Hirosi.

1986-01-01

Cultured SQ-1979 cells of C3H mouse squamous cell carcinomas in logarithmic growth phase were treated with either pepleomycin (PEP) or bleomycin (BLM), alone or in combination with X-rays. The lethal effect of PEP on the SQ cells was greater than that of BLM. The survival curves of the cells were biphasic at concentrations examined (5 to 60 μg/ml) of PEP. The survival depended on the concentration and treatment time up to 3 hr. The cells treated with BLM showed biphasic survival curves also. Regarding combined effects of either PEP or BLM and X-rays, there was no significant difference in the survival curves between the group with X-rays and the group with X-rays and drug. When a drug was given 4 hr after exposure to X-rays rather than before that, synergistic action of the drug and X-rays was attained. This was marked for PEP. (Namekawa, K.)

Somatic and germline mosaicism for a mutation of the PHEX gene can lead to genetic transmission of X-linked hypophosphatemic rickets that mimics an autosomal dominant trait.

Science.gov (United States)

Goji, Katsumi; Ozaki, Kayo; Sadewa, Ahmad H; Nishio, Hisahide; Matsuo, Masafumi

2006-02-01

Familial hypophosphatemic rickets is usually transmitted as an X-linked dominant disorder (XLH), although autosomal dominant forms have also been observed. Genetic studies of these disorders have identified mutations in PHEX and FGF23 as the causes of X-linked dominant disorder and autosomal dominant forms, respectively. The objective of the study was to describe the molecular genetic findings in a family affected by hypophosphatemic rickets with presumed autosomal dominant inheritance. We studied a family in which the father and the elder of his two daughters, but not the second daughter, were affected by hypophosphatemic rickets. The pedigree interpretation of the family suggested that genetic transmission of the disorder occurred as an autosomal dominant trait. Direct nucleotide sequencing of FGF23 and PHEX revealed that the elder daughter was heterozygous for an R567X mutation in PHEX, rather than FGF23, suggesting that the genetic transmission occurred as an X-linked dominant trait. Unexpectedly, the father was heterozygous for this mutation. Single-nucleotide primer extension and denaturing HPLC analysis of the father using DNA from single hair roots revealed that he was a somatic mosaic for the mutation. Haplotype analysis confirmed that the father transmitted the genotypes for 18 markers on the X chromosome equally to his two daughters. The fact that the father transmitted the mutation to only one of his two daughters indicated that he was a germline mosaic for the mutation. Somatic and germline mosaicism for an X-linked dominant mutation in PHEX may mimic autosomal dominant inheritance.

Studies on the effects of adriamycin-derivatives in combination with X-rays on MeWo- and Be11-cells

International Nuclear Information System (INIS)

Krueger, M.; Beuningen, D. van; Streffer, C.

1990-01-01

The survival rate of human melanoma cells after X-ray irradiation, treamtment with adriamycin derivatives and combined treatment with X-rays and adriamycin derivatives was measured by means of the colony formation test. After X-ray irradiation the melanoma cells showed a high resistance for cell survival. In all tests the Be11-cells were more resistant than MeWo-cells. On combined exposure especially with higher doses of adriamycin derivatives, both cell lines showed the interesting effect, that with increasing concentration the survival rate decreased whereas the D 0 increased. Aclacinomycin-A (ACM-A) and Pirarubicin reduced recovery processes after X-ray irradiation. Therefore Be11-cells showed a four times higher DMF (dosis modifying factor) after ACM-A-treatment than MeWo-cells. Low ACM-A-concentrations combined with low X-ray doses showed on both cell lines supraadditive effects. The effect of pirarubicin was in most of the tests only additive. Compared with ACM-A, pirarubicin was less cytotoxic, showed a larger therapeutic range, caused a smaller D 0 and D q and had a supraadditive effect in low concentrations on both cell lines. For clinical combined therapy with patients ACM-A is probably better suited than pirarubicin. (orig.) [de

Effect of Co content on magnetic and optical properties of Zn1−xCoxOy nanorods

International Nuclear Information System (INIS)

Chen, Jia-Hong; Lin, Yow-Jon; Chang, Hsing-Cheng; Chen, Ya-Hui; Horng, Lance; Chang, Chia-Chi

2013-01-01

Highlights: ► The magnetic and optical properties of Zn 1−x Co x O y nanorods were studied. ► The ferromagnetic properties arise from the replacement of Zn by Co and defects. ► A link between the magnetization, nanorod sizes and defects was established. - Abstract: The effect of Co content on the magnetic and optical properties of Zn 1−x Co x O y nanorods have been investigated in this study. X-ray diffraction, energy dispersive spectrometer, photoluminescence and ferromagnetism measurements were used to characterize the Zn 1−x Co x O y nanorods. It is shown that the ferromagnetic properties arise from the replacement of Zn by Co in the ZnO lattice. Combining with photoluminescence and scanning electron microscopic results, a direct link between the magnetization, nanorod sizes and acceptor defects of Zn 1−x Co x O y nanorods was established.

New opportunities for 3D materials science of polycrystalline materials at the micrometre lengthscale by combined use of X-ray diffraction and X-ray imaging

DEFF Research Database (Denmark)

Ludwig, W.; King, A.; Reischig, P.

2009-01-01

Non-destructive, three-dimensional (3D) characterization of the grain structure in mono-phase polycrystalline materials is an open challenge in material science. Recent advances in synchrotron based X-ray imaging and diffraction techniques offer interesting possibilities for mapping 3D grain shapes....... A recent extension of this methodology, termed X-ray diffraction contrast tomography (DCT), combines the principles of X-ray diffraction imaging, three-dimensional X-ray diffraction microscopy (3DXRD) and image reconstruction from projections. DCT provides simultaneous access to 3D grain shape...

Combination of expansion and orthognathic surgery in a severe hyperdivergent skeletal Class III malocclusion

Directory of Open Access Journals (Sweden)

Anadha Gujar

2016-01-01

Full Text Available Class III malocclusions with a severe hyperdivergent growth pattern are very complex to plan and treat. This case report describes the treatment of an adult with a skeletal Class III malocclusion with a midface deficiency, severe bilateral posterior crossbite, and a severe hyperdivergent growth pattern by a combination of a bonded rapid maxillary expansion appliance and surgical procedure of Le Fort I osteotomy for maxillary advancement.

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Renal involvement in the immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) disorder.

Science.gov (United States)

Sheikine, Yuri; Woda, Craig B; Lee, Pui Y; Chatila, Talal A; Keles, Sevgi; Charbonnier, Louis-Marie; Schmidt, Birgitta; Rosen, Seymour; Rodig, Nancy M

2015-07-01

Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) disorder is an autoimmune disease caused by loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor. These mutations affect the normal function of circulating regulatory T cells. IPEX is characterized by profound immune dysregulation leading to dermatitis, enteropathy, multiple endocrinopathies and failure to thrive. Different forms of renal injury have also been noted in these patients but these have been described to a very limited extent. Three patients with IPEX with characteristic renal findings and mutations in FOXP3, including one novel mutation, are described. Case presentations are followed by a review of the renal manifestations noted in IPEX and the range of therapeutic options for this disorder. We recommend that IPEX be considered in the differential diagnosis of young children who present with signs of immune dysregulation with a concomitant renal biopsy demonstrating immune complex deposition in a membranous-like pattern and/or interstitial nephritis.

Extensive X-linked adaptive evolution in central chimpanzees

DEFF Research Database (Denmark)

Hvilsom, Christina; Qian, Yu; Bataillon, Thomas

2012-01-01

on the dominance of beneficial (adaptive) and deleterious mutations. Here we capture and sequence the complete exomes of 12 chimpanzees and present the largest set of protein-coding polymorphism to date. We report extensive adaptive evolution specifically targeting the X chromosome of chimpanzees with as much...... to humans, we find that purifying selection is stronger on the X chromosome than on the autosomes in chimpanzees. We therefore conclude that most adaptive mutations are recessive. We also document dramatically reduced synonymous diversity in the chimpanzee X chromosome relative to autosomes and stronger...... purifying selection than for the human X chromosome. If similar processes were operating in the human-chimpanzee ancestor as in central chimpanzees today, our results therefore provide an explanation for the much-discussed reduction in the human-chimpanzee divergence at the X chromosome....

Feelings Associated with Being a Carrier and Characteristics of Reproductive Decision Making in Women Known to Be Carriers of X-linked Conditions.

Science.gov (United States)

Kay, Elizabeth; Kingston, Helen

2002-03-01

Qualitative data were collected from 14 women known to be carriers of an X-linked condition associated with 'serious' disability on feelings about being a carrier and impact on reproductive decisions. Guilt and responsibility were commonly expressed by carriers about issues surrounding pregnancy. Personal experience of the condition influenced their approach to reproductive decisions. Those who had lived with an affected brother were more concrete in their decisions to avoid having an affected child compared to those with less personal experience of the condition. It is concluded that feelings of guilt associated with difficult reproductive decisions are reflected in the strong sense of responsibility attached to being a carrier. Personal experience of the condition has a clear influence on reproductive decisions of X-linked carriers.

A Phex Mutation in a Murine Model of X-linked Hypophosphatemia Alters Phosphate Responsiveness of Bone Cells

OpenAIRE

Ichikawa, Shoji; Austin, Anthony M.; Gray, Amie K.; Econs, Michael J.

2012-01-01

Mutations in the PHEX gene cause X-linked hypophosphatemia (XLH). Hypophosphatemia in XLH results from increased circulating levels of a phosphaturic hormone, fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D (calcitriol) synthesis. The current standard therapy for XLH – high dose phosphate and calcitriol – further increases FGF23 concentrations, suggesting that patients with XLH may have an altered response to extracellular phosphate...

Association of Cross Linked C-Telopeptide II Collagen and Hyaluronic Acid with Knee Osteoarthritis Severity

Directory of Open Access Journals (Sweden)

John Butar Butar

2013-12-01

Full Text Available BACKGROUND: This study was carried out to investigate the association of Cross Linked C-Telopeptide Type I & II Collagen (CTX-I and II and hyaluronic acid (HA with knee osteoarthritis (OA severity. METHODS: Sixty menopause women with primary knee OA were enrolled in this study during their visits to the Outpatient Department. Patients with knee pain during weight bearing, active or passive range of motion, or tenderness with Kellgren-Lawrence (KL grade of more than I were included. Patients with injury, inflammatory and metabolic diseases were excluded. Patients were put in a 10-hour fasting prior to withdrawal of morning blood samples for examinations of HA, CTX-I, interleukin 1 beta (IL-1β, and high sensitivity C reactive protein (hs-CRP level. Second void morning urine specimens were taken for CTXII assessment. HA, CTX-I and II levels were measured by enzyme-linked immunosorbent assay. RESULTS: Sixty menopausal female patients were included in this study, 35 with KL grade II, 17 grade III, and 8 grade IV. Means of CTX-II were significantly different between subjects KL grade IV and III (p=0.021. Correlation of KL grade was significant with CTX-II (p=0.001, r=0.412 and HA (p=0.0411, r=0.269. KL grades were not significantly associated with CTX-I (p=0.8364, r=-0.0272; IL-1β (p=0.5773, r=0.0853 and hs-CRP (p=0.2625, r=0.1470. CONCLUSIONS: CTX-II and HA were associated with severity of knee OA, suggesting that CTX-II and HA can be used as marker for knee OA severity. KEYWORDS: CTX-II, hyaluronic acid, otestoarthritis, knee.

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Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation

DEFF Research Database (Denmark)

Freude, Kristine; Hoffmann, Kirsten; Jensen, Lars-Riff

2004-01-01

Nonsyndromic X-linked mental retardation (NSXLMR) is a very heterogeneous condition, and most of the underlying gene defects are still unknown. Recently, we have shown that approximately 30% of these genes cluster on the proximal Xp, which prompted us to perform systematic mutation screening...

X-chromosome inactivation patterns in monozygotic twins and sib pairs discordant for nonsyndromic cleft lip and/or palate

DEFF Research Database (Denmark)

Kimani, Jane W; Shi, Min; Daack-Hirsch, Sandra

2007-01-01

Nonsyndromic clefts of the lip and/or palate are common birth defects with a strong genetic component. Based on unequal gender ratios for clefting phenotypes, evidence for linkage to the X chromosome and the occurrence of several X-linked clefting syndromes, we investigated the role of skewed X c...

The central nervous system phenotype of X-linked Charcot-Marie-Tooth disease: a transient disorder of children and young adults.

Science.gov (United States)

Al-Mateen, Majeed; Craig, Alexa Kanwit; Chance, Phillip F

2014-03-01

We describe 2 patients with X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) disease and central nervous system manifestations and review 19 cases from the literature. Our first case had not been previously diagnosed with Charcot-Marie-Tooth disease, and the second case, although known to have Charcot-Marie-Tooth disease, was suspected of having CMTX1 after presentation with central nervous system manifestations. The most common central nervous system manifestations were transient and included dysarthria, ataxia, hemiparesis, and tetraparesis resembling periodic paralysis. Of the 21 patients, 19 presented at 21 years of age or younger, implicating CMTX1 with transient central nervous system manifestations as a disorder that predominantly affects children and adolescents. CMTX1 should be included in the differential diagnosis of patients who present with transient central nervous system phenomena, including stroke-like episodes, tetraparesis suggestive of periodic paralysis, dysarthria, ataxia, or combinations of these deficits. Reversible, bilateral, nonenhancing white matter lesions and restricted diffusion on magnetic resonance imaging are characteristic features of the central nervous system phenotype of CMTX1.

Synergistic effect of anti-angiogenic herbal composition (Meta-X) in combination with radiotherapy on the inhibition of tumor growth

International Nuclear Information System (INIS)

Han, Young Soo; Song, Jie Young; Yoon, Yeon Sook; Kim, Joon Sik; Park, Byung Young; Lee, Hee Suk; Kim, Min Yung

2004-01-01

Anti-angiogenic composition called Meta-X was made from herbal medicines that are currently used oral drugs for other indications. We examined biochemical properties of Meta-X, and synergistic effect of Meta-X combined with irradiation on the inhibition of tumor growth

Synergistic effect of anti-angiogenic herbal composition (Meta-X) in combination with radiotherapy on the inhibition of tumor growth

Energy Technology Data Exchange (ETDEWEB)

Han, Young Soo; Song, Jie Young; Yoon, Yeon Sook [Korea Institute of Radilolgical and Medical Science, Seoul (Korea, Republic of); Kim, Joon Sik; Park, Byung Young; Lee, Hee Suk; Kim, Min Yung [AngioLab, Seoul (Korea, Republic of)

2004-07-01

Anti-angiogenic composition called Meta-X was made from herbal medicines that are currently used oral drugs for other indications. We examined biochemical properties of Meta-X, and synergistic effect of Meta-X combined with irradiation on the inhibition of tumor growth.

X-ray holography with an atomic scatterer

Energy Technology Data Exchange (ETDEWEB)

Mityureva, A.A.; Smirnov, V.V., E-mail: valery_smirnov@mail.ru

2016-08-15

X-ray holography scheme with reference scatterer consisting of heavy atom as reference center and its link to an object consisting of several light atoms and using controlled variation of the alignment is represented. The scheme can reproduce an object in three dimensions with atomic resolution. The distorting factors of reconstruction are considered. - Highlights: • X-ray holography scheme with a reference wave formed by atomic scatterer. • 3D object reconstruction with atomic resolution from the set of holograms. • Simple formula for the distorting factor in reconstruction.

Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

Science.gov (United States)

Naves, Luciana A; Daly, Adrian F; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Júnior, Armindo Jreige; Neto, Florêncio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S; Stratakis, Constantine A; Lupski, James R; Beckers, Albert

2016-02-01

X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.

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Probing the influence of X-rays on aqueous copper solutions using time-resolved in situ combined video/X-ray absorption near-edge/ultraviolet-visible spectroscopy

NARCIS (Netherlands)

Mesu, J. Gerbrand; Beale, Andrew M.; de Groot, Frank M. F.; Weckhuysen, Bert M.

2006-01-01

Time-resolved in situ video monitoring and ultraviolet-visible spectroscopy in combination with X-ray absorption near-edge spectroscopy (XANES) have been used for the first time in a combined manner to study the effect of synchrotron radiation on a series of homogeneous aqueous copper solutions in a

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry.

Science.gov (United States)

Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K H

2016-08-01

Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240-fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Gigantism: X-linked acrogigantism and GPR101 mutations.

Science.gov (United States)

Iacovazzo, Donato; Korbonits, Márta

X-linked acrogigantism (XLAG) is a recently identified condition of early-onset GH excess resulting from the germline or somatic duplication of the GPR101 gene on chromosome Xq26.3. Thirty patients have been formally reported so far. The disease affects mostly females, occurs usually sporadically, and is characterised by early onset and marked overgrowth. Most patients present with concomitant hyperprolactinaemia. Histopathology shows pituitary hyperplasia or pituitary adenoma with or without associated hyperplasia. XLAG-related pituitary adenomas present peculiar histopathological features that should contribute to raise the suspicion of this rare condition. Treatment is frequently challenging and multi-modal. While females present with germline mutations, the sporadic male patients reported so far were somatic mosaics with variable levels of mosaicism, although no differences in the clinical phenotype were observed between patients with germline or somatic duplication. The GPR101 gene encodes an orphan G protein-coupled receptor normally expressed in the central nervous system, and at particularly high levels in the hypothalamus. While the physiological function and the endogenous ligand of GPR101 are unknown, the high expression of GPR101 in the arcuate nucleus and the occurrence of increased circulating GHRH levels in some patients with XLAG, suggest that increased hypothalamic GHRH secretion could play a role in the pathogenesis of this condition. In this review, we summarise the published evidence on XLAG and GPR101 and discuss the results of recent studies that have investigated the potential role of GPR101 variants in the pathogenesis of pituitary adenomas. Copyright © 2016 Elsevier Ltd. All rights reserved.

Familial colorectal cancer type X

DEFF Research Database (Denmark)

Dominguez-Valentin, Mev; Therkildsen, Christina; Da Silva, Sabrina

2015-01-01

Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic...... features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention....

A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets

Directory of Open Access Journals (Sweden)

Tetsuya Kawahara

2015-01-01

Full Text Available X-linked hypophosphatemic rickets (XLH is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. Inactivating mutations in the gene encoding phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX have been found to be associated with XLH. Here, we report a 16-year-old female patient affected by hypophosphatemic rickets. We evaluated her serum fibroblast growth factor 23 (FGF23 levels and conducted sequence analysis of the disease-associated genes of FGF23-related hypophosphatemic rickets: PHEX, FGF23, dentin matrix protein 1, and ectonucleotide pyrophosphatase/phosphodiesterase 1. She was diagnosed with XLH based on her clinical features and family history. Additionally, we observed elevated FGF23 levels and a novel PHEX exon 9 mutation (c.947G>T; p.Gly316Val inherited from her father. Although bioinformatics showed that the mutation was neutral, Gly316 is perfectly conserved among humans, mice, and rats, and there were no mutations in other FGF23-related rickets genes, suggesting that in silico analysis is limited in determining mutation pathogenicity. In summary, we present a female patient and her father with XLH harboring a novel PHEX mutation that appears to be causative of disease. Measurement of FGF23 for hypophosphatemic patients is therefore useful for the diagnosis of FGF23-dependent hypophosphatemia.

Efficacy of vitreoretinal surgery in the treatment of X-linked retinoschisis with serious complications

Directory of Open Access Journals (Sweden)

Chen Zhao

2013-10-01

Full Text Available AIM: To evaluate the efficacy of vitreoretinal surgery in the treatment of X-linked retinoschisis(XLRSand its complications. METHODS: A retrospective study was made on all the XLRS patients with severe complications after operation in this hospital. All the 25 patients(31 eyespresent with macular abnormalities with/without peripheral retina split bypreoperative OCT examination. Among the 31 eyes, there were 7 eyes with vitreous hemorrhage, 8 eyes with retinal detachment and vitreous hemorrhage, and 16 eyes with rhegmatogenous retinal detachment. All the 31 eyes were divided into 2 groups: group A included 15 eyes which underwent photocoagulation before the surgery, while the other 16 eyes in group B didn't perform photocoagulation before the surgery. All the patients underwent a pars plana vitrectomy without lensectomy associated with internal limiting membrane peeling. Photocoagulation was done to the retinal holes and degeneration areas in group A. Gas or silicone oil was filled in group B after retinal photocoagulation treatment. Three years later, analysis was made on the results of the visual acuity, postoperative anatomical and functional outcome in these 2 groups. Statistical analysis was made on the results of average visual acuity before and after operation by SPSS software method, the difference was statistically significant(PRESULTS: Postoperative anatomical and functional outcome were satisfied at the last visit. A total of 23 eyes'(74.2%visual acuity were improved with the mean visual acuity increasing from 0.13±0.08 to 0.24±0.16, the difference was statistically significant(t=-5.354,P=0.000. The average visual acuity in group A was improved from 0.11±0.08 to 0.22±0.15 after operation(t=-4.391, P=0.000. While the average visual acuity in group B increased from 0.14±0.08 to 0.26±0.15(t=-4.488, P=0.000. The visual changes in two groups were statistical significance. But when compared the average changes of visual acuity before

A study on quantifying COPD severity by combining pulmonary function tests and CT image analysis

Science.gov (United States)

Nimura, Yukitaka; Kitasaka, Takayuki; Honma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Mori, Kensaku

2011-03-01

This paper describes a novel method that can evaluate chronic obstructive pulmonary disease (COPD) severity by combining measurements of pulmonary function tests and measurements obtained from CT image analysis. There is no cure for COPD. However, with regular medical care and consistent patient compliance with treatments and lifestyle changes, the symptoms of COPD can be minimized and progression of the disease can be slowed. Therefore, many diagnosis methods based on CT image analysis have been proposed for quantifying COPD. Most of diagnosis methods for COPD extract the lesions as low-attenuation areas (LAA) by thresholding and evaluate the COPD severity by calculating the LAA in the lung (LAA%). However, COPD is usually the result of a combination of two conditions, emphysema and chronic obstructive bronchitis. Therefore, the previous methods based on only LAA% do not work well. The proposed method utilizes both of information including the measurements of pulmonary function tests and the results of the chest CT image analysis to evaluate the COPD severity. In this paper, we utilize a multi-class AdaBoost to combine both of information and classify the COPD severity into five stages automatically. The experimental results revealed that the accuracy rate of the proposed method was 88.9% (resubstitution scheme) and 64.4% (leave-one-out scheme).

A longitudinal study of visual function in carriers of X-linked recessive retinitis pigmentosa.

Science.gov (United States)

Grover, S; Fishman, G A; Anderson, R J; Lindeman, M

2000-02-01

This study was carried out to evaluate the progression of visual function impairment in carriers of X-linked recessive retinitis pigmentosa. We also assessed the relationship between the retinal findings at presentation and the extent of deterioration. Observational, retrospective, case series. Twenty-seven carriers of X-linked recessive retinitis pigmentosa. Each carrier was clinically categorized into one of four grades (grades 0 through 3) depending on the presence or absence of a tapetal-like retinal reflex and the extent of peripheral pigmentary degeneration. A complete ophthalmologic examination was performed and data for visual acuity, visual field area, and electroretinographic measurements were collected on the most recent visit in both eyes. These were then compared with similar data obtained on their initial visits. A comparison of visual function was carried out between the initial visit and the most recent visit on each carrier. The visual acuity was measured with Snellen's acuity charts. The visual fields to targets V-4-e and II-4-e were planimeterized and used for the analysis. The electroretinographic (ERG) measures used were light-adapted single-flash b-wave amplitudes and 30-Hz red flicker for cone function, dark-adapted maximal b-wave amplitudes, and response to a low intensity blue-flash for rod function. None of the 11 carriers with a tapetal-like reflex only (grade 1) showed any significant change in visual acuity or fields as compared with 3 of 7 (43%) carriers with diffuse peripheral pigmentary findings (grade 3) who showed significant deterioration in visual acuity in at least one eye, and 6 of 7 (86%) who showed a significant decrease in visual field area with at least one target size in at least one eye. By comparison, only 1 of 10 carriers with a grade 1 fundus finding demonstrated a significant decrease in maximal dark-adapted ERG function as compared with 5 of 6 (83%) carriers with grade 3 in response to a single-flash stimulus and

Dry heat and radiation combination effects on Aspergillus flavus Link. infecting cocoa beans

International Nuclear Information System (INIS)

Amoako-Atta, B.; Meier, H.; Odamtten, G.T.

1981-01-01

The paper deals with the effect of heat and radiation combination treatments on the control of microbial spoilage of cocoa beans caused by toxigenic Aspergillus flavus Link. The heat and radiation sources were from dry air oven heat and 60 Co gammacell 220 irradiator, respectively. The radiation doses used were either 0, 50, 100, 150 or 200 krad, with combined heat temperatures of 30, 60 or 90 0 C. At each temperature level three different exposure time intervals of either 15 min, 30 min or 60 min respectively, were used. Two reversible sequential heat/radiation combination effects were evaluated. The first sequence involved cocoa beans inoculated with A. flavus spores exposed first to dry heat at pre-determined temperature heat exposure time, followed by radiation treatment, then retention of samples in a constant humidity environmental chamber set at 80% for daily observation up to forty days post-treatment. The second sequence involved exposure of the inoculated beans first to radiation, then to heat before retention under fixed RH for observation. From their results, the authors arrive at four conclusions: first, that there is a critical radiation/heat combination range (200, 150 and 100 krad/90 0 C for 15 min) that significantly decontaminates (less than 5% mouldiness) A. flavus infected cocoa beans even under high relative humidity (80% RH) environment; second, that a temperature level of 90 0 C combined with 200, 150 or 100 krad maximizes such effect but the heat exposure time is a major factor; third, that low heat temperature ranges of 30 or 60 0 C, combined with low radiation dosages of 150 krad or below, enhance the rate of A. flavus spoilage effects of cocoa beans; and, lastly, that the sequence of exposure of the inoculated cocoa beans to heat/radiation combination influenced the spore germination; exposure to heat before radiation would sensitize the spores (200 krad/90 0 C) but results in an increased radioresistance. (author)

Performance of a Combined System Using an X-Ray FEL Oscillator and a High-Gain FEL Amplifier

Energy Technology Data Exchange (ETDEWEB)

Gupta, L.; Lindberg, R.; Kim, K. -J.

2017-06-01

The LCLS-II at SLAC will feature a 4 GeV CW superconducting (SC) RF linac [1] that can potentially drive a 5th harmonic X-Ray FEL Oscillator (XFELO) to produce fully coherent, 1 MW photon pulses with a 5 meV bandwidth at 14.4 keV [2]. The XFELO output can serve as the input seed signal for a high-gain FEL amplifier employing fs electron beams from the normal conducting SLAC linac, thereby generating coherent, fs x-ray pulses with TW peak powers using a tapered undulator after saturation [3]. Coherent, intense output at several tens of keV will also be feasible if one considers a harmonic generation scheme. Thus, one can potentially reach the 42 keV photon energy required for the MaRIE project [4] by beginning with an XFELO operating at the 3rd harmonic to produce 14.0 keV photons using a 12 GeV SCRF linac, and then subsequently using the high-gain harmonic generation scheme to generate and amplify the 3th harmonic at 42 keV [5]. We report extensive GINGER simulations that determine an optimized parameter set for the combined system.

X-linked congenital adrenal hypoplasia associated with hypospadias in an Egyptian baby: a case report

Directory of Open Access Journals (Sweden)

Metwalley Kotb

2012-12-01

Full Text Available Abstract Introduction X-linked congenital adrenal hypoplasia is a rare developmental disorder of the human adrenal cortex and is caused by deletion or mutation of the dosage-sensitive sex reversal adrenal hypoplasia congenita critical region of the X chromosome, gene 1 (DAX-1 gene. Most affected children present with failure to thrive, salt wasting and hypoglycemic convulsions in the first months of life. Hypospadias affects approximately one in 250 live male births. Mutations in the mastermind-like domain-containing 1 (MAMLD1 gene have been implicated as one of the causes of hypospadias in children. To the best of our knowledge, an association between congenital adrenal hypoplasia due to a DAX-1 mutation and hypospadias due to mutation of the MAMLD1 gene has not previously been reported in the literature. Case presentation A 35-day-old male Egyptian baby was referred to our institution for the evaluation of a two-week history of recurrent vomiting associated with electrolyte imbalance. On examination, our patient was found to have hypotension and dehydration. A genital examination showed distal penile hypospadias with chordee and normal testes. He had hyponatremia, hyperkalemia, hypoglycemia and metabolic acidosis. Endocrinological investigations revealed low levels of cortisol, 17-hydroxyprogesterone and aldosterone, with a high level of adrenocorticotrophic hormone. A provisional diagnosis of congenital adrenal hypoplasia associated with hypospadias was made. A molecular genetics study confirmed the diagnosis of X-linked congenital adrenal hypoplasia due to DAX-1 mutations and hypospadias due to MAMLD1 mutation. He was started on hydrocortisone and fludrocortisone treatment. After three weeks of treatment, his symptoms improved and his blood sugar, sodium, potassium and cortisol levels normalized. Conclusions We report the case of an Egyptian baby with an association of congenital adrenal hypoplasia due to DAX-1 mutation and hypospadias due

Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy

Energy Technology Data Exchange (ETDEWEB)

Beggs, A.H.; Neumann, P.E.; Anderson, M.S.; Kunkel, L.M. (Harvard Medical School, Boston, MA (United States)); Arahata, Kiichi; Arikawa, Eri; Nonaka, Ikuya (National Inst. of Neuroscience, Tokyo (Japan))

1992-01-15

Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3,500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, the authors propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative to Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.

X-ray diagnosis of bronchial obstruction in chronic pneumonia

International Nuclear Information System (INIS)

Mamilyaev, R.M.

1981-01-01

Combined radiobronchological examination of patients with chronic pneumonia in the phase of reverse development of the disease has been performed. Severity, localization and extent of bronchial obstruction have been studied, depending on the phase of chronic pneumonia and aspects of lung tissue alterations. Bronchial lesions characteristic of chronic pneumonia were defined, as well as importance of x-ray examination methods for bronchial obstruction diagnosis. Three types of bronchial obstruction were distinguished: bronchoconstriction, bronchodilatation and their combination. With regard to the character and severity of bronchial and pulmonary tissue lesions 3 variants of chronic pneumonia are offered to be differentiated: bronchitic, bronchoectatic, and abscess-forming. The main significance in diagnosis of chronic pneumonia is attributed to combined x-ray examination, which also includes radiobronchological investigation in the first two variants of the disease [ru

X-linked dominant protoporphyria: The first reported Japanese case.

Science.gov (United States)

Ninomiya, Yukiko; Kokunai, Yasuhito; Tanizaki, Hideaki; Akasaka, Eijiro; Nakano, Hajime; Moriwaki, Shinichi

2016-04-01

A 12-year-old boy with photosensitivity since 3 years of age presented with small concavities on both cheeks, the nasal root and the dorsal surface of both hands. According to the clinical features, erythropoietic protoporphyria (EPP) was suspected. Urine and blood samples were tested for porphyrin derivatives, which revealed a markedly elevated level of erythrocyte protoporphyrin (EP) and a diagnosis of EPP was made. The patient's mother had no photosensitivity, however, lesions appearing slightly as small scars were found on the dorsum of her right hand; his elder sister and father showed no rash. The EP levels were elevated in samples from his mother and mildly elevated in those from his elder sister and father. To obtain a definitive diagnosis, genetic analyses were performed using samples from all family members, which revealed no mutations in the ferrochelatase-encoding gene (FECH), which is responsible for EPP. Instead, a pathological mutation of the 5-aminolevulinic acid synthase-encoding gene (ALAS2) was identified in samples from the patient, his mother and his elder sister, confirming a definitive diagnosis of X-linked dominant protoporphyria (XLDPP). This is the first Japanese family reported to have XLDPP, demonstrating evidence of the condition in Japan. In addition, because XLDPP is very similar to EPP in its clinical aspects and laboratory findings, a genetic analysis is required for the differential diagnosis. © 2015 Japanese Dermatological Association.

Combined use of infrared and hard X-ray microprobes for spectroscopy-based neuroanatomy

Science.gov (United States)

Surowka, A. D.; Ziomber, A.; Czyzycki, M.; Migliori, A.; Pieklo, L.; Kasper, K.; Szczerbowska-Boruchowska, M.

2018-05-01

Understanding the pathological triggers that affect the structural and physiological integrity of biochemical milieu of neurons is crucial to extend our knowledge on brain disorders, that are in many circumstances hardly treatable. Over recently, by using sophisticated hyperspectral micro-imaging modalities, it has been placed within our reach to get an insight into high fidelity histological details along with corresponding biochemical information in a label-free fashion, without using any additional chemical fixatives. However, in order to push forwards extensive application of these methods in the clinical arena, it is viable to make further iterations in novel data analysis protocols in order to boost their sensitivity. Therefore, in our study we proposed a new combined approach utilizing both benchtop Fourier transform infrared (FTIR) and synchrotron X-ray fluorescence (SR-XRF) micro-spectroscopies coupled with multivariate data clustering using the K-means algorithm for combined molecular and elemental micro-imaging, so that these complimentary analytical tools could be used for delineating between various brain structures based on their biochemical composition. By utilizing mid-IR transmission FTIR experiments, the biochemical composition in terms of lipids, proteins and phosphodiesters became accessible. In turn, the SR-XRF experiment was carried out at the advanced IAEA X-ray spectrometry station at Elettra Sincrotrone Trieste. By measuring in vacuum and by using the primary exciting X-ray beam, monochromatized to 10.5 keV, we took advantage of accessing the characteristic X-ray lines of a variety of elements ranging from carbon to zinc. Herein, we can report that the developed methodology has high specificity for label-free discriminating between lipid- and protein-rich brain tissue areas.

Clinical optical coherence tomography combined with multiphoton tomography for evaluation of several skin disorders

Science.gov (United States)

König, Karsten; Speicher, Marco; Bückle, Rainer; Reckfort, Julia; McKenzie, Gordon; Welzel, Julia; Koehler, Martin J.; Elsner, Peter; Kaatz, Martin

2010-02-01

The first clinical trial of optical coherence tomography (OCT) combined with multiphoton tomography (MPT) and dermoscopy is reported. State-of-the-art (i) OCT systems for dermatology (e.g. multibeam swept source OCT), (ii) the femtosecond laser multiphoton tomograph DermaInspectTM, and (iii) digital dermoscopes were applied to 47 patients with a diversity of skin diseases and disorders such as skin cancer, psoriasis, hemangioma, connective tissue diseases, pigmented lesions, and autoimmune bullous skin diseases. Dermoscopy, also called 'epiluminescent microscopy', provides two-dimensional color images of the skin surface. OCT imaging is based on the detection of optical reflections within the tissue measured interferometrically whereas nonlinear excitation of endogenous fluorophores and the second harmonic generation are the bases of MPT images. OCT cross sectional "wide field" image provides a typical field of view of 5 x 2 mm2 and offers fast information on the depth and the volume of the investigated lesion. In comparison, multiphoton tomography presents 0.36 x 0.36 mm2 horizontal or diagonal sections of the region of interest within seconds with submicron resolution and down to a tissue depth of 200 μm. The combination of OCT and MPT provides a synergistic optical imaging modality for early detection of skin cancer and other skin diseases.

A Call to Include Severe Combined Immunodeficiency in Newborn Screening Program

OpenAIRE

Raz Somech; Amos Etzioni

2014-01-01

Quantification of the T cell receptor excision circles (TRECs) has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID) or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of co...

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

OpenAIRE

Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on bra...

Mutilating keratoderma with concomitant alopecia and keratoses follicularis spinulosa decalvans: X-linked olmsted syndrome and its response to isotretinoin

Directory of Open Access Journals (Sweden)

Gunjan Verma

2017-01-01

Full Text Available We report a case of mutilating keratoderma with alopecia and keratoses follicularis spinulosa decalvans (KFSD, which was initially diagnosed as ectodermal dysplasia and Olmsted syndrome but was revisited as a case of X-linked Olmsted (XLO syndrome. We focus on this uncommon entity (XLO to highlight the differentials of alopecia with palmoplantar keratoderma.

Genetics Home Reference: X-linked dilated cardiomyopathy

Science.gov (United States)

... The other conditions in the spectrum, Duchenne and Becker muscular dystrophy , are characterized by progressive weakness and wasting of ... linked dilated cardiomyopathy is sometimes classified as subclinical Becker muscular dystrophy. Related Information What does it mean if a ...

Influence of 1,2-PB matrix cross-linking on structure and properties of selectively etched 1,2-PB-b-PDMS block copolymers

DEFF Research Database (Denmark)

Guo, Fengxiao; Andreasen, Jens Wenzel; Vigild, Martin Etchells

2007-01-01

of the cross-linked samples in toluene was converted into a degree of cross-linking following the Flory scheme; a simple relation between the Flory cross-linking degree and the fraction of consumed double bonds during the cross-linking reaction followed. The structure of the block copolymer at different stages...... of preparation was characterized by small-angle X-ray scattering (SAXS). In addition, scanning electron microscopy (SEM) gave direct images of the nanoporous polymer structure. Nanocavities are accessible to methanol, and observations of methanol uptake were combined with structural information from SAXS...

Enhanced lethal effect of combined ACNU with x-ray on cultured HeLaS3 cells

International Nuclear Information System (INIS)

Kanazawa, Haruyuki; Miyamoto, Tadaaki

1983-01-01

The combined effects of ACNU and X-irradiation on cultured HeLaS 3 cells were investigated. Pretreatment with either ACNU or X-ray induced a substantial reduction in shoulder width the D 0 value of the dose-response curve for the other agent, given later was unchanged. ACNU did not inhibit the recovery of sublethal damage (SLD) induced by X-ray when this treatment preceded the spilit-dose experiment. Our results indicate that some cell damage induced by each agent is transmissible to the progeny of the surviving cells and that the interaction of ACNU and X-irradiation was lethal to the cells. (author)

First report on an X-linked hypohidrotic ectodermal dysplasia family with X chromosome inversion: Breakpoint mapping reveals the pathogenic mechanism and preimplantation genetics diagnosis achieves an unaffected birth.

Science.gov (United States)

Wu, Tonghua; Yin, Biao; Zhu, Yuanchang; Li, Guangui; Ye, Lijun; Liang, Desheng; Zeng, Yong

2017-12-01

To investigate the etiology of X-linked hypohidrotic ectodermal dysplasia (XLHED) in a family with an inversion of the X chromosome [inv(X)(p21q13)] and to achieve a healthy birth following preimplantation genetic diagnosis (PGD). Next generation sequencing (NGS) and Sanger sequencing analysis were carried out to define the inversion breakpoint. Multiple displacement amplification, amplification of breakpoint junction fragments, Sanger sequencing of exon 1 of ED1, haplotyping of informative short tandem repeat markers and gender determination were performed for PGD. NGS data of the proband sample revealed that the size of the possible inverted fragment was over 42Mb, spanning from position 26, 814, 206 to position 69, 231, 915 on the X chromosome. The breakpoints were confirmed by Sanger sequencing. A total of 5 blastocyst embryos underwent trophectoderm biopsy. Two embryos were diagnosed as carriers and three were unaffected. Two unaffected blastocysts were transferred and a singleton pregnancy was achieved. Following confirmation by prenatal diagnosis, a healthy baby was delivered. This is the first report of an XLHED family with inv(X). ED1 is disrupted by the X chromosome inversion in this XLHED family and embryos with the X chromosomal abnormality can be accurately identified by means of PGD. Copyright © 2017. Published by Elsevier B.V.

PPM-X: A new X-linked mental retardation syndrome with psychosis, pyramidal signs, and macroorchidism maps to Xq28

Energy Technology Data Exchange (ETDEWEB)

Lindsay, S.; Splitt, M.; Edney, S. [Univ. of Newcastle upon Tyne (United Kingdom)] [and others

1996-06-01

We report a three-generation family manifesting a previously undescribed X-linked mental retardation syndrome. Four of the six moderately retarded males have had episodes of manic-depressive psychosis. The phenotype also includes pyramidal signs, Parkinsonian features, and macroorchidism, but there are no characteristic dysmorphic facial features. Affected males do not show fragile sites at distal Xq on cytogenetic analysis, nor do they have expansions of the CGG repeats at the FRAXA, FRAXE, or FRAXF loci. Linkage analyses were undertaken, and a maximal LOD score of 3.311 at {theta} = .0 was observed with the microsatellite marker DXS1123 in Xq28. A recombination was detected in one of the affected males with DXS1691 (Xq28), which gives the proximal boundary of the localization. No distal recombination has been detected at any of the loci tested. 31 refs., 2 figs., 2 tabs.

Combining ability of opium poppy genotypes over F1 and F2 generations of 8x8 diallel cross

Directory of Open Access Journals (Sweden)

Hemant Kumar Yadav

2009-01-01

Full Text Available Combining abilities for yield, its component traits and morphine content were examined in opium poppy tounderstand the inheritance pattern of these traits, and to identify genotypes suitable for genetic improvement of yield andmorphine content. The experiment comprising a total of 64 treatments (28 F1+28 F2 and 8 parents was evaluated in RBD. Theresults showed that most of the traits are governed by non additive gene action however additive gene action is also important.The parents BR-232, BR-245, BR-234 were found to be good general combiners for yield and its related traits and can beutilized in multiple breeding programs. SCA effects in relation to GCA effects of parents showed that most of the crosscombinations with high SCA effects involved high x high, high x low and low x low GCA combiners.

P2X purinoceptors as a link between hyperexcitability and neuroinflammation in status epilepticus.

Science.gov (United States)

Henshall, David C; Engel, Tobias

2015-08-01

There remains a need for more efficacious treatments for status epilepticus. Prolonged seizures result in the release of ATP from cells which activates the P2 class of ionotropic and metabotropic purinoceptors. The P2X receptors gate depolarizing sodium and calcium entry and are expressed by both neurons and glia throughout the brain, and a number of subtypes are upregulated after status epilepticus. Recent studies have explored the in vivo effects of targeting ATP-gated P2X receptors in preclinical models of status epilepticus, with particular focus on the P2X7 receptor (P2X7R). The P2X7R mediates microglial activation and the release of the proepileptogenic inflammatory cytokine interleukin 1β. The receptor may also directly modulate neurotransmission and gliotransmission and promote the recruitment of immune cells into brain parenchyma. Data from our group and collaborators show that status epilepticus produced by intraamygdala microinjection of kainic acid increases P2X7R expression in the hippocampus and neocortex of mice. Antagonism of the P2X7R in the model reduced seizure severity, microglial activation and interleukin 1β release, and neuronal injury. Coadministration of a P2X7R antagonist with a benzodiazepine also provided seizure suppression in a model of drug-refractory status epilepticus when either treatment alone was minimally effective. More recently, we showed that status epilepticus in immature rats is also reduced by P2X7R antagonism. Together, these findings suggest that P2X receptors may be novel targets for seizure control and interruption of neuroinflammation after status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Magnetic Resonance Imaging Features as Surrogate Markers of X-Linked Hypophosphatemic Rickets Activity.

Science.gov (United States)

Lempicki, Marta; Rothenbuhler, Anya; Merzoug, Valérie; Franchi-Abella, Stéphanie; Chaussain, Catherine; Adamsbaum, Catherine; Linglart, Agnès

2017-01-01

X-linked hypophosphatemic rickets (XLH) is the most common form of inheritable rickets. Rickets treatment is monitored by assessing alkaline phosphatase (ALP) levels, clinical features, and radiographs. Our objectives were to describe the magnetic resonance imaging (MRI) features of XLH and to assess correlations with disease activity. Twenty-seven XLH patients (median age 9.2 years) were included in this prospective single-center observational study. XLH activity was assessed using height, leg bowing, dental abscess history, and serum ALP levels. We looked for correlations between MRI features and markers of disease activity. On MRI, the median maximum width of the physis was 5.6 mm (range 4.8-7.8; normal 1.5 mm in all of the patients. The appearance of the zone of provisional calcification was abnormal on 21 MRI images (78%), Harris lines were present on 24 (89%), and bone marrow signal abnormalities were present on 16 (59%). ALP levels correlated with the maximum physeal widening and with the transverse extent of the widening. MRI of the knee provides precise rickets patterns that are correlated with ALP, an established biochemical marker of the disease, avoiding X-ray exposure and providing surrogate quantitative markers of disease activity. © 2017 S. Karger AG, Basel.

X-linked juvenile retinoschisis: mutations at the retinoschisis and Norrie disease gene loci?

Science.gov (United States)

Hiraoka, M; Rossi, F; Trese, M T; Shastry, B S

2001-01-01

Juvenile retinoschisis (RS) and Norrie disease (ND) are X-linked recessive retinal disorders. Both disorders, in the majority of cases, are monogenic and are caused by mutations in the RS and ND genes, respectively. Here we report the identification of a family in which mutations in both the RS and ND genes are segregating with RS pathology. Although the mutations identified in this report were not functionally characterized with regard to their pathogenicity, it is likely that both of them are involved in RS pathology in the family analyzed. This suggests the complexity and digenic nature of monogenic human disorders in some cases. If this proves to be a widespread problem, it will complicate the strategies used to identify the genes involved in diseases and to develop methods for intervention.

Observations of several disruptions in PLT using soft and ultra-soft x-ray radiation

International Nuclear Information System (INIS)

Eames, D.R.; von Goeler, S.; Sauthoff, N.R.; Stodiek, W.

1979-03-01

The evolution of ultra-soft x-ray radiation (USX, hν approx. > 100 eV) is compared to that of the soft x-ray radiation (SX, hν approx. > 1000 eV) during several disruptions in PLT. Spatial resolution is obtained in both cases by arrays of silicon surface barrier detectors viewing along different chords. During some disruptions the USX behaves quite differently from the SX, and a classification is made based on the USX behavior. Different interpretations of the data are discussed, along with the possibility that these measurements may distinguish between the roles of temperature and impurity density changes during disruptions

Maternal and paternal parenting styles: unique and combined links to adolescent and early adult delinquency.

Science.gov (United States)

Hoeve, Machteld; Dubas, Judith Semon; Gerris, Jan R M; van der Laan, Peter H; Smeenk, Wilma

2011-10-01

The present study examines the cross-sectional and longitudinal associations between fathers' and mothers' parenting styles and male and female delinquency using a sample of 330 Dutch families with a mid or late adolescent son or daughter (ages 14-22), followed across two measurement waves with a 5-year interval. Parenting styles of fathers and mothers were linked to delinquency. A significant parenting style by sex interaction was found: neglectful parenting was related to higher levels of delinquency in males and permissive parenting was linked to delinquency in females. A long term relationship was found between fathers' neglectful parenting style and delinquency in males. Furthermore, results revealed that levels of delinquency were the lowest in families with at least one authoritative parent and highest in families with two neglectful parents, indicating that the level of delinquency was dependent on the combination of mother's and father's parenting styles. Copyright © 2011 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Cytogenetic analysis and response to ionizing radiations in a girl with severe muscular dystrophy

International Nuclear Information System (INIS)

Meola, G.; Barsi, L.; Velicogna, M.; Scarlato, G.; Fuhrman-Conti, A.M.

1988-01-01

Duchenne Muscular Dystrophy (DMD) is a severe X-linked condition characterized by a progressive degeneration of skeletal muscle. Mild clinical symptoms have been reported in female carriers of the DMD gene with normal karyotypes, this occurs in about 8% of DMD carriers. The degree of manifestation ranges from pseudohypertrophy of the calf muscles to moderate myopathy with proximal muscle wasting and weakness. Such manifestations can be explained on the basis of preferential inactivation of the X chromosome bearing the normal allele. The authors describe the cytogenetic analysis and the response to ionizing radiations in a severely affected girl exhibiting clinical, neurophysiological, biochemical, and histological findings of DMD

Allelic heterogeneity and genetic modifier loci contribute to clinical variation in males with X-linked retinitis pigmentosa due to RPGR mutations.

Directory of Open Access Journals (Sweden)

Abigail T Fahim

Full Text Available Mutations in RPGR account for over 70% of X-linked retinitis pigmentosa (XlRP, characterized by retinal degeneration and eventual blindness. The clinical consequences of RPGR mutations are highly varied, even among individuals with the same mutation: males demonstrate a wide range of clinical severity, and female carriers may or may not be affected. This study describes the phenotypic diversity in a cohort of 98 affected males from 56 families with RPGR mutations, and demonstrates the contribution of genetic factors (i.e., allelic heterogeneity and genetic modifiers to this diversity. Patients were categorized as grade 1 (mild, 2 (moderate or 3 (severe according to specific clinical criteria. Patient DNAs were genotyped for coding SNPs in 4 candidate modifier genes with products known to interact with RPGR protein: RPGRIP1, RPGRIP1L, CEP290, and IQCB1. Family-based association testing was performed using PLINK. A wide range of clinical severity was observed both between and within families. Patients with mutations in exons 1-14 were more severely affected than those with ORF15 mutations, and patients with predicted null alleles were more severely affected than those predicted to make RPGR protein. Two SNPs showed association with severe disease: the minor allele (N of I393N in IQCB1 (p = 0.044 and the common allele (R of R744Q in RPGRIP1L (p = 0.049. These data demonstrate that allelic heterogeneity contributes to phenotypic diversity in XlRP and suggest that this may depend on the presence or absence of RPGR protein. In addition, common variants in 2 proteins known to interact with RPGR are associated with severe disease in this cohort.

Hybrid Strategies for Link Adaptation Exploiting Several Degrees of Freedom in OFDM Based Broadband Wireless Systems

DEFF Research Database (Denmark)

Das, Suvra S.; Rahman, Muhammad Imadur; Wang, Yuanye

2007-01-01

In orthogonal frequency division multiplexing (OFDM) systems, there are several degrees of freedom in time and frequency domain, such as, sub-band size, forward error control coding (FEC) rate, modulation order, power level, modulation adaptation interval, coding rate adaptation interval and powe...... of the link parameters based on the channel conditions would lead to highly complex systems with high overhead. Hybrid strategies to vary the adaptation rates to tradeoff achievable efficiency and complexity are presented in this work....

New opportunities for 3D materials science of polycrystalline materials at the micrometre lengthscale by combined use of X-ray diffraction and X-ray imaging

Energy Technology Data Exchange (ETDEWEB)

Ludwig, W., E-mail: ludwig@esrf.fr [Universite de Lyon, INSA-Lyon, MATEIS CNRS UMR 5510, 69621Villeurbanne (France); European Synchrotron Radiation Facility, BP220, 38043 Grenoble (France); King, A. [European Synchrotron Radiation Facility, BP220, 38043 Grenoble (France); School of Materials, University of Manchester, Manchester, M13 9PL (United Kingdom); Reischig, P. [European Synchrotron Radiation Facility, BP220, 38043 Grenoble (France); Herbig, M. [Universite de Lyon, INSA-Lyon, MATEIS CNRS UMR 5510, 69621Villeurbanne (France); Lauridsen, E.M.; Schmidt, S. [Riso National Laboratory for Sustainable Energy, Technical University of Denmark, P.O. Box 49, DK-4000 Roskilde (Denmark); Proudhon, H.; Forest, S. [MINES ParisTech, Centre des materiaux, CNRS UMR 7633, BP 87, 91003 Evry Cedex (France); Cloetens, P.; Roscoat, S. Rolland du [European Synchrotron Radiation Facility, BP220, 38043 Grenoble (France); Buffiere, J.Y. [Universite de Lyon, INSA-Lyon, MATEIS CNRS UMR 5510, 69621Villeurbanne (France); Marrow, T.J. [School of Materials, University of Manchester, Manchester, M13 9PL (United Kingdom); Poulsen, H.F. [Riso National Laboratory for Sustainable Energy, Technical University of Denmark, P.O. Box 49, DK-4000 Roskilde (Denmark)

2009-10-25

Non-destructive, three-dimensional (3D) characterization of the grain structure in mono-phase polycrystalline materials is an open challenge in material science. Recent advances in synchrotron based X-ray imaging and diffraction techniques offer interesting possibilities for mapping 3D grain shapes and crystallographic orientations for certain categories of polycrystalline materials. Direct visualisation of the three-dimensional grain boundary network or of two-phase (duplex) grain structures by means of absorption and/or phase contrast techniques may be possible, but is restricted to specific material systems. A recent extension of this methodology, termed X-ray diffraction contrast tomography (DCT), combines the principles of X-ray diffraction imaging, three-dimensional X-ray diffraction microscopy (3DXRD) and image reconstruction from projections. DCT provides simultaneous access to 3D grain shape, crystallographic orientation and local attenuation coefficient distribution. The technique applies to the larger range of plastically undeformed, polycrystalline mono-phase materials, provided some conditions on grain size and texture are fulfilled. The straightforward combination with high-resolution microtomography opens interesting new possibilities for the observation of microstructure related damage and deformation mechanisms in these materials.

New opportunities for 3D materials science of polycrystalline materials at the micrometre lengthscale by combined use of X-ray diffraction and X-ray imaging

International Nuclear Information System (INIS)

Ludwig, W.; King, A.; Reischig, P.; Herbig, M.; Lauridsen, E.M.; Schmidt, S.; Proudhon, H.; Forest, S.; Cloetens, P.; Roscoat, S. Rolland du; Buffiere, J.Y.; Marrow, T.J.; Poulsen, H.F.

2009-01-01

Non-destructive, three-dimensional (3D) characterization of the grain structure in mono-phase polycrystalline materials is an open challenge in material science. Recent advances in synchrotron based X-ray imaging and diffraction techniques offer interesting possibilities for mapping 3D grain shapes and crystallographic orientations for certain categories of polycrystalline materials. Direct visualisation of the three-dimensional grain boundary network or of two-phase (duplex) grain structures by means of absorption and/or phase contrast techniques may be possible, but is restricted to specific material systems. A recent extension of this methodology, termed X-ray diffraction contrast tomography (DCT), combines the principles of X-ray diffraction imaging, three-dimensional X-ray diffraction microscopy (3DXRD) and image reconstruction from projections. DCT provides simultaneous access to 3D grain shape, crystallographic orientation and local attenuation coefficient distribution. The technique applies to the larger range of plastically undeformed, polycrystalline mono-phase materials, provided some conditions on grain size and texture are fulfilled. The straightforward combination with high-resolution microtomography opens interesting new possibilities for the observation of microstructure related damage and deformation mechanisms in these materials.

Hard X-Ray PHA System on the HT-7 Tokamak

International Nuclear Information System (INIS)

Lin Shiyao; Shi Yuejiang; Wan Baonian; Chen Zhongyong; Hu Liqun

2006-01-01

A new hard X-ray pulse-height analysis (PHA) system has been established on HT-7 tokamak for long pulse steady-state operation. This PHA system consists of hard X-ray diagnostics and multi-channel analysers (MCA). The hard X-ray diagnostics consists of a vertical X-ray detector array (CdTe) and a horizontal X-ray detector array (NaI). The hard X-ray diagnostics can provide the profile of power deposition and the distribution function of fast electron during radio frequency (RF) current drive. The MCA system is the electronic part of the PHA system, which has been modularized and linked to PC through LAN. Each module of MCA can connect with 8 X-ray detectors. The embedded Ethernet adapter in the MCA module makes the data communication between PC and MCA very convenient. A computer can control several modules of MCA through certain software and a hub. The RAM in MCA can store 1024 or more spectra for each detector and therefore the PHA system can be applied in the long pulse discharge of several minutes

Combined X-ray and neutron fibre diffraction studies of biological and synthetic polymers

International Nuclear Information System (INIS)

Parrot, I.M.; Urban, V.; Gardner, K.H.; Forsyth, V.T.

2005-01-01

The fibrous state is a natural one for polymer molecules which tend to assume regular helical conformations rather than the globular structures characteristic of many proteins. Fibre diffraction therefore has broad application to the study of a wide range of biological and synthetic polymers. The purpose of this paper is to illustrate the general scope of the method and in particular to demonstrate the impact of a combined approach involving both X-ray and neutron diffraction methods. While the flux of modern X-ray synchrotron radiation sources allows high quality datasets to be recorded with good resolution within a very short space of time, neutron studies can provide unique information through the ability to locate hydrogen or deuterium atoms that are often difficult or impossible to locate using X-ray methods. Furthermore, neutron fibre diffraction methods can, through the ability to selectively label specific parts of a structure, be used to highlight novel aspects of polymer structure that can not be studied using X-rays. Two examples are given. The first describes X-ray and neutron diffraction studies of conformational transitions in DNA. The second describes structural studies of the synthetic high-performance polymer poly(p-phenylene terephthalamide) (PPTA), known commercially as Kevlar[reg] or Twaron[reg

Combined X-ray and neutron fibre diffraction studies of biological and synthetic polymers.

Energy Technology Data Exchange (ETDEWEB)

Parrot, I. M. [Institut Laue-Langevin (ILL); Urban, Volker S [ORNL; Gardner, K. H. [DuPont Experimental Station; Forsyth, V. T. [Institut Laue Langevin and Keele University

2005-04-01

The fibrous state is a natural one for polymer molecules which tend to assume regular helical conformations rather than the globular structures characteristic of many proteins. Fibre diffraction therefore has broad application to the study of a wide range of biological and synthetic polymers. The purpose of this paper is to illustrate the general scope of the method and in particular to demonstrate the impact of a combined approach involving both X-ray and neutron diffraction methods. While the flux of modern X-ray synchrotron radiation sources allows high quality datasets to be recorded with good resolution within a very short space of time, neutron studies can provide unique information through the ability to locate hydrogen or deuterium atoms that are often difficult or impossible to locate using X-ray methods. Furthermore, neutron fibre diffraction methods can, through the ability to selectively label specific parts of a structure, be used to highlight novel aspects of polymer structure that can not be studied using X-rays. Two examples are given. The first describes X-ray and neutron diffraction studies of conformational transitions in DNA. The second describes structural studies of the synthetic high-performance polymer poly(p-phenylene terephthalamide) (PPTA), known commercially as Kevlar{reg_sign} or Twaron{reg_sign}.

Combined X-ray and neutron fibre diffraction studies of biological and synthetic polymers

Science.gov (United States)

Parrot, I. M.; Urban, V.; Gardner, K. H.; Forsyth, V. T.

2005-08-01

The fibrous state is a natural one for polymer molecules which tend to assume regular helical conformations rather than the globular structures characteristic of many proteins. Fibre diffraction therefore has broad application to the study of a wide range of biological and synthetic polymers. The purpose of this paper is to illustrate the general scope of the method and in particular to demonstrate the impact of a combined approach involving both X-ray and neutron diffraction methods. While the flux of modern X-ray synchrotron radiation sources allows high quality datasets to be recorded with good resolution within a very short space of time, neutron studies can provide unique information through the ability to locate hydrogen or deuterium atoms that are often difficult or impossible to locate using X-ray methods. Furthermore, neutron fibre diffraction methods can, through the ability to selectively label specific parts of a structure, be used to highlight novel aspects of polymer structure that can not be studied using X-rays. Two examples are given. The first describes X-ray and neutron diffraction studies of conformational transitions in DNA. The second describes structural studies of the synthetic high-performance polymer poly(p-phenylene terephthalamide) (PPTA), known commercially as Kevlar® or Twaron®.

Combined X-ray and neutron fibre diffraction studies of biological and synthetic polymers

Energy Technology Data Exchange (ETDEWEB)

Parrot, I.M. [Institut Laue Langevin, 6 Rue Jules Horowitz, 38042 Grenoble Cedex 9 (France); Institute of Science and Technology in Medicine, Keele University Medical School, Staffordshire ST4 7QB (United Kingdom); Urban, V. [Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, TN 37831-6100 (United States); Gardner, K.H. [Department of Materials Science and Engineering University of Delaware, Newark, DE 19719 (United States); Forsyth, V.T. [Institut Laue Langevin, 6 Rue Jules Horowitz, 38042 Grenoble Cedex 9 (France) and Institute of Science and Technology in Medicine, Keele University Medical School, Staffordshire ST4 7QB (United Kingdom)]. E-mail: tforsyth@ill.fr

2005-08-15

The fibrous state is a natural one for polymer molecules which tend to assume regular helical conformations rather than the globular structures characteristic of many proteins. Fibre diffraction therefore has broad application to the study of a wide range of biological and synthetic polymers. The purpose of this paper is to illustrate the general scope of the method and in particular to demonstrate the impact of a combined approach involving both X-ray and neutron diffraction methods. While the flux of modern X-ray synchrotron radiation sources allows high quality datasets to be recorded with good resolution within a very short space of time, neutron studies can provide unique information through the ability to locate hydrogen or deuterium atoms that are often difficult or impossible to locate using X-ray methods. Furthermore, neutron fibre diffraction methods can, through the ability to selectively label specific parts of a structure, be used to highlight novel aspects of polymer structure that can not be studied using X-rays. Two examples are given. The first describes X-ray and neutron diffraction studies of conformational transitions in DNA. The second describes structural studies of the synthetic high-performance polymer poly(p-phenylene terephthalamide) (PPTA), known commercially as Kevlar[reg] or Twaron[reg].

Scatter and transmission doses from several pediatric X-ray examinations in a nursery

International Nuclear Information System (INIS)

Burrage, John W.; Rampant, Peter L.; Beeson, Brendan P.

2003-01-01

While several studies have investigated the dose from scattered radiation from X-ray procedures in a pediatric nursery, they examined scatter from chest procedures only, or the types of examination were not specified. The aim of this study was to collect scatter and transmission data from several types of X-ray examinations. Using a ''newborn'' anthropomorphic phantom and an ion chamber, a series of scatter and transmission dose measurements were performed using typical exposure factors for chest, chest and abdomen, skull, skeletal long bone and spine procedures. The phantom was inside a crib for all exposures. The maximum scatter dose measured at 1 m from the field center was about 0.05 μGy per exposure for lateral skulls. Transmission doses for lateral exams were around 0.1 μGy per exposure at 1 m from the isocenter. The study demonstrated that scatter dose to other patients in a neonatal unit is not significant, assuming the distance between adjacent cribs is in the order of 1 m. Transmission doses are also low provided the beam is fully intercepted by the cassette. For an average workload the dose received by imaging technologists would be small. (orig.)

Combined ellipsometry and X-ray related techniques for studies of ultrathin organic nanocomposite films

Energy Technology Data Exchange (ETDEWEB)

Kraemer, Markus, E-mail: axo@standing-waves.d [Leibniz-Institut fuer Analytische Wissenschaften-ISAS-e.V., Bunsen-Kirchhoff-Str. 11, 44139 Dortmund (Germany); AXO DRESDEN GmbH, Siegfried-Raedel-Str. 31, 01809 Heidenau (Germany); Roodenko, Katy [Leibniz-Institut fuer Analytische Wissenschaften-ISAS-e.V.-Department Berlin, Albert-Einstein-Str. 9, 12489 Berlin (Germany); Laboratory for Surface and Nanostructure Modification, University of Texas at Dallas-NSERL, 800W. Campbell Rd., Richardson, TX 75080 (United States); Pollakowski, Beatrix [Physikalisch-Technische Bundesanstalt, Abbestr. 2-12, 10587 Berlin (Germany); Hinrichs, Karsten [Leibniz-Institut fuer Analytische Wissenschaften-ISAS-e.V.-Department Berlin, Albert-Einstein-Str. 9, 12489 Berlin (Germany); Rappich, Joerg [Helmholtz-Zentrum Berlin fuer Materialien und Energie GmbH, Abteilung Silizium-Photovoltaik, Kekulestr. 5, 12489 Berlin (Germany); Esser, Norbert [Leibniz-Institut fuer Analytische Wissenschaften-ISAS-e.V.-Department Berlin, Albert-Einstein-Str. 9, 12489 Berlin (Germany); Bohlen, Alex von; Hergenroeder, Roland [Leibniz-Institut fuer Analytische Wissenschaften-ISAS-e.V., Bunsen-Kirchhoff-Str. 11, 44139 Dortmund (Germany)

2010-07-30

Ultrathin nanocomposite films of nitrobenzene on silicon were analyzed by Infrared Spectroscopic Ellipsometry (IRSE), X-ray reflectivity (XRR) and X-ray standing waves (XSW) before and after evaporation of gold. Infrared Spectroscopic Ellipsometry measurements were performed for identification of adsorbates and for investigation of the molecular orientation. Results for film thickness were correlated with XRR measurements. Further, XSW measurements of elements incorporated in nitrobenzene (C, N, and O) were performed with soft X-rays. The combination of the different methods allowed to confirm a model for the electrochemically deposited nitrobenzene films before and after gold evaporation. The characterization by XRR and XSW scans using hard X-rays showed that gold had penetrated into the nitrobenzene film and thus changed density and optical properties of this layer significantly. A depth profile correlated to the electron density is deduced from the XRR measurements. This profile allows to localize-in vertical direction-gold islands within the composite film.

Probing structural homogeneity of La{sub 1-x}Gd{sub x}PO{sub 4} monazite-type solid solutions by combined spectroscopic and computational studies

Energy Technology Data Exchange (ETDEWEB)

Huittinen, N., E-mail: n.huittinen@hzdr.de [Helmholtz-Zentrum Dresden - Rossendorf, Institute of Resource Ecology, Bautzner Landstraße 400, 01328 Dresden (Germany); Arinicheva, Y. [Forschungszentrum Jülich GmbH, Institute of Energy and Climate Research, Nuclear Waste Management and Reactor Safety (IEK-6), 52425 Jülich (Germany); Kowalski, P.M.; Vinograd, V.L. [Forschungszentrum Jülich GmbH, Institute of Energy and Climate Research, Nuclear Waste Management and Reactor Safety (IEK-6), 52425 Jülich (Germany); JARA High-Performance Computing, Schinkelstraße 2, 52062 Aachen (Germany); Neumeier, S. [Forschungszentrum Jülich GmbH, Institute of Energy and Climate Research, Nuclear Waste Management and Reactor Safety (IEK-6), 52425 Jülich (Germany); Bosbach, D. [Forschungszentrum Jülich GmbH, Institute of Energy and Climate Research, Nuclear Waste Management and Reactor Safety (IEK-6), 52425 Jülich (Germany); JARA High-Performance Computing, Schinkelstraße 2, 52062 Aachen (Germany)

2017-04-01

Here we study the homogeneity of Eu{sup 3+}-doped La{sub 1-x}Gd{sub x}PO{sub 4} (x = 0, 0.11, 0.33, 0.55, 0.75, 0.92, 1) monazite-type solid solutions by a combination of Raman and time-resolved laser fluorescence spectroscopies (TRLFS) with complementary quasi-random structure-based atomistic modeling studies. For the intermediate La{sub 0.45}Gd{sub 0.55}PO{sub 4} composition we detected a significant broadening of the Raman bands corresponding to the lattice vibrations of the LnO{sub 9} polyhedron, indicating much stronger distortion of the lanthanide cation site than the PO{sub 4} tetrahedron. A distortion of the crystal lattice around the dopant site was also confirmed in our TRLFS measurements of Eu{sup 3+} doped samples, where both the half width (FWHM) of the excitation peaks and the {sup 7}F{sub 2}/{sup 7}F{sub 1} ratio derived from the emission spectra increase for intermediate solid-solution compositions. The observed variation in FWHM correlates well with the simulated distribution of Eu···O bond distances within the investigated monazites. The combined results imply that homogenous Eu{sup 3+}-doped La{sub 1-x}Gd{sub x}PO{sub 4} monazite-type solid solutions are formed over the entire composition range, which is of importance in the context of using these ceramics for immobilization of radionuclides. - Highlights: •Homogenous Eu{sup 3+}-doped La{sub 1-x}Gd{sub x}PO{sub 4} monazite-type solid solutions have been synthesized. •Solid solution formation is accompanied by slight distortion of the LnO{sub 9} polyhedron. •Raman and laser spectroscopic trends are observed within the monazite series. •Results are explained with atomistic simulations of Eu-O bond distance distribution.

A PRACTICAL APPROACH TO THE DETECTION OF ANDROGEN RECEPTOR GENE-MUTATIONS AND PEDIGREE ANALYSIS IN FAMILIES WITH X-LINKED ANDROGEN INSENSITIVITY

NARCIS (Netherlands)

RISSTALPERS, C; HOOGENBOEZEM, T; SLEDDENS, HFBM; VERLEUNMOOIJMAN, MCT; DEGENHART, HJ; DROP, SLS; HALLEY, DJJ; Oosterwijk, Jan; HODGINS, MB; TRAPMAN, J; BRINKMANN, AO

Androgen insensitivity syndrome (AIS) is an X-linked disorder in which defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46,XY individuals. This survey reports the analysis of 11 AIS subjects. The androgen receptor gene of

A practical approach to the detection of androgen receptor gene mutations and pedigree analysis in families with x-linked androgen insensitivity

NARCIS (Netherlands)

Ris-Stalpers, C.; Hoogenboezem, T.; Sleddens, H. F.; Verleun-Mooijman, M. C.; Degenhart, H. J.; Drop, S. L.; Halley, D. J.; Oosterwijk, J. C.; Hodgins, M. B.; Trapman, J.

1994-01-01

Androgen insensitivity syndrome (AIS) is an X-linked disorder in which defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46,XY individuals. This survey reports the analysis of 11 AIS subjects. The androgen receptor gene of

Deciphering Late-Pleistocence landscape evolution: linking proxies by combining pedo-stratigraphy and luminescence dating

Science.gov (United States)

Kreutzer, Sebastian; Meszner, Sascha; Faust, Dominik; Fuchs, Markus

2014-05-01

Interpreting former landscape evolution asks for understanding the processes that sculpt such landforms by means of deciphering complex systems. For reconstructing terrestrial Quaternary environments based on loess archives this might be considered, at least, as a three step process: (1) Identifying valuable records in appropriate morphological positions in a previously defined research area, (2) analysing the profiles by field work and laboratory methods and finally (3) linking the previously considered pseudo-isolated systems to set up a comprehensive picture. Especially the first and the last step might bring some pitfalls, as it is tempting to specify single records as pseudo-isolated, closed systems. They might be, with regard to their preservation in their specific morphological position, but in fact they are part of a complex, open system. Between 2008 and 2013, Late-Pleistocene loess archives in Saxony have been intensively investigated by field and laboratory methods. Linking pedo- and luminescence dating based chronostratigraphies, a composite profile for the entire Saxonian Loess Region has been established. With this, at least, two-fold approach we tried to avoid misinterpretations that might appear when focussing on one standard profile in an open morphological system. Our contribution focuses on this multi-proxy approach to decipher the Late-Pleistocene landscape evolution in the Saxonian Loess Region. Highlighting the challenges and advantages of combining different methods, we believe that (1) this multi-proxy approach is without alternative, (2) the combination of different profiles may simplify the more complex reality, but it may be a useful generalisation to understand and reveal the stratigraphical significance of the landscape evolution in this region.

[Experimental model of severe local radiation injuries of the skin after X-rays].

Science.gov (United States)

Kotenko, K V; Moroz, B B; Nasonova, T A; Dobrynina, O A; LIpengolz, A A; Gimadova, T I; Deshevoy, Yu B; Lebedev, V G; Lyrschikova, A V; Eremin, I I

2013-01-01

The experimental model of severe local radiation injuries skin under the influence of a relatively soft X-rays on a modified device RAP 100-10 produced by "Diagnostica-M" (Russia) was proposed. The model can be used as pre-clinical studies in small experimental animals in order to improve the treatment of local radiation injuries, especially in the conditions of application of cellular therapy.

Multichannel, sequential or combined X-ray spectrometry

International Nuclear Information System (INIS)

Florestan, J.

1979-01-01

X-ray spectrometer qualities and defects are evaluated for sequential and multichannel categories. Multichannel X-ray spectrometer has time-coherency advantage and its results could be more reproducible; on the other hand some spatial incoherency limits low percentage and traces applications, specially when backgrounds are very variable. In this last case, sequential X-ray spectrometer would find again great usefulness [fr

Modeling X-linked ancestral origins in multiparental populations

NARCIS (Netherlands)

Zheng, Chaozhi

2015-01-01

The models for the mosaic structure of an individual's genome from multiparental populations have been developed primarily for autosomes, whereas X chromosomes receive very little attention. In this paper, we extend our previous approach to model ancestral origin processes along two X chromosomes

PDA-phone-based instant transmission of radiological images over a CDMA network by combining the PACS screen with a Bluetooth-interfaced local wireless link.

Science.gov (United States)

Kim, Dong Keun; Yoo, Sun K; Park, Jeong Jin; Kim, Sun Ho

2007-06-01

Remote teleconsultation by specialists is important for timely, correct, and specialized emergency surgical and medical decision making. In this paper, we designed a new personal digital assistant (PDA)-phone-based emergency teleradiology system by combining cellular communication with Bluetooth-interfaced local wireless links. The mobility and portability resulting from the use of PDAs and wireless communication can provide a more effective means of emergency teleconsultation without requiring the user to be limited to a fixed location. Moreover, it enables synchronized radiological image sharing between the attending physician in the emergency room and the remote specialist on picture archiving and communication system terminals without distorted image acquisition. To enable rapid and fine-quality radiological image transmission over a cellular network in a secure manner, progressive compression and security mechanisms have been incorporated. The proposed system is tested over a code division Multiple Access 1x-Evolution Data-Only network to evaluate the performance and to demonstrate the feasibility of this system in a real-world setting.

X-linked adrenoleukodystrophy: correlation between Loes score and diffusion tensor imaging parameters.

Science.gov (United States)

Ono, Sergio Eiji; de Carvalho Neto, Arnolfo; Gasparetto, Emerson Leandro; Coelho, Luiz Otávio de Mattos; Escuissato, Dante Luiz; Bonfim, Carmem Maria Sales; Ribeiro, Lisandro Lima

2014-01-01

The present study was aimed at evaluating the correlation between diffusion tensor imaging parameters and Loes score as well as whether those parameters could indicate early structural alterations. Diffusion tensor imaging measurements were obtained in 30 studies of 14 patients with X-linked adrenoleukodystrophy and were correlated with Loes scores. A control group including 28 male patients was created to establish agematched diffusion tensor imaging measurements. Inter- and intraobserver statistical analyses were undertaken. Diffusion tensor imaging measurements presented strong Pearson correlation coefficients (r) of -0.86, 0.89, 0.89 and 0.84 for fractional anisotropy and mean, radial and axial diffusivities (p tensor measurements at early stage of the disease indicates that mean and radial diffusivities might be useful to predict the disease progression. Measurements of diffusion tensor parameters can be used as an adjunct to the Loes score, aiding in the monitoring of the disease and alerting for possible Loes score progression in the range of interest for therapeutic decisions.

Modification of chromosomal aberration and polyploidy by combined treatment with x-rays and colchicine in Trichosanthes anguina

International Nuclear Information System (INIS)

Datta, S.K.; Basu, R.K.

1978-01-01

Mitosis in root tip cells of T. anguina after treatment of seeds with X-rays, colchicine and in combination of the two was studied. X-irradiation resulted in cells with chromosomal aberrations, which increased with increase in doses. With increase in colchicine concentrations there was decrease in diploid cells with consequent increase in polyploid cells. Post-irradiation colchicine treatment resulted in both aberrant and polyploid cells but their frequencies were less than separate treatment with X-rays and colchicine respectively. (author)

Refined mapping and YAC contig construction of the X-linked cleft palate and ankyloglossia locus (CPX) including the proximal X-Y homology breakpoint within Xq21.3

Energy Technology Data Exchange (ETDEWEB)

Forbes, S.A.; Brennan, L.; Richardson, M. [Queen Charlotte`s Hospital, London (United Kingdom)] [and others

1996-01-01

The gene for X-linked cleft palate (CPX) has previously been mapped in an Icelandic kindred between the unordered proximal markers DXS1002/DXS349/DXS95 and the distal marker DXYS1X, which maps to the proximal end of the X-Y homology region in Xq21.3. Using six sequence-tagged sites (STSs) within the region, a total of 91 yeast artificial chromosome (YAC) clones were isolated and overlapped in a single contig that spans approximately 3.1 Mb between DXS1002 and DXYS1X. The order of microsatellite and STS markers in this was established as DXS1002-DXS1168-DXS349-DXS95-DXS364-DXS1196-DXS472-DXS1217-DXYS1X. A long-range restriction map of this region was created using eight nonchimeric, overlapping YAC clones. Analysis of newly positioned polymorphic markers in recombinant individuals from the Icelandic family has enabled us to identify DXS1196 and DXS1217 as the flanking markers for CPX. The maximum physical distance containing the CPX gene has been estimated to be 2.0 Mb, which is spanned by a minimum set of five nonchimeric YAC clones. In addition, YAC end clone and STS analyses have pinpointed the location of the proximal boundary of the X-Y homology region within the map. 40 refs., 2 figs., 2 tabs.

A Synoptic Climatology of Combined Severe/Weather/Flash Flood Events

Science.gov (United States)

Pallozzi, Kyle J.

Classical forms of severe weather such as tornadoes, damaging convective wind gusts, and large hail, as well as flash flooding events, all have potentially large societal impacts. This impact is further magnified when these hazards occur simultaneously in time and space. A major challenge for operational forecasters is how to accurately predict the occurrence of combined storm hazards, and how to communicate the associated multiple threat hazards to the public. A seven-year climatology (2009-2015) of combined severe weather/flash flooding (SVR/FF) events across the contiguous United States was developed in attempt to study the combined SVR/FF event hazards further. A total of 211 total cases were identified and sub-divided into seven subcategories based on their convective morphology and meteorological characteristics. Heatmaps of event report frequency were created to extract spatial, seasonal and interannual patterns in SVR/FF event activity. Diurnal trends were examined from time series plots of tornado, hail, wind and flash flood/flood reports. Event-centered composites of environmental variables were created for each subcategory from 13 km RUC/RAP analyses. Representative cases studies were conducted for each subcategory. A "ring of fire" with the highest levels of SVR/FF event activity was noted across the central United States. SVR/FF events were least common in the Southeast, High Plains, and Northern Plains. Enhanced SVR/FF activity reflected contributions from synoptic events during the cool and shoulder seasons over the Lower Mississippi, Arkansas and Tennessee Valleys, and MCS activity during the warm season over the lower Great Plains, and the Upper Mississippi, Missouri and Ohio River Valleys. Results from the composite analyses indicated that relatively high values of CAPE, surface-500 hPa shear and precipitable water were observed for all subcategories. Case studies show that many high-end SVR/FF events featured slow-moving, or quasi

Optimization of a spectrometry for energy-dispersive x-ray fluorescence analysis by x-ray tube in combination with secondary target for multielements determination of sediment samples

International Nuclear Information System (INIS)

Zaidi Embong; Husin Wagiran

1997-01-01

The design of an energy-dispersive X-ray fluorescence spectrometer equipped with a conventional X-ray tube and secondary target is described. The spectrometer system constructed in our laboratory consists of a semiconductor detector system, irradiation chamber and X-ray tube. Primary source from X-ray tube was used to produced secondary X-ray from selenium, molybdenum and cadmium targets. The fluorescence X-ray from the sample was detected using Si(Li) detector with resolution of 0. 175 keV (Mn-K(x). The spectrometer was used for determination of multi-elements with atomic number between 20 to 44 in river sediment samples. The X-ray spectrum, from the samples were analysed using computer software which was developed based on Marquardt method. Optimal conditions and detection limits are determined experimentally by variation of excitation parameters for each combination of secondary target and tube voltage

A quasi-realtime x-ray microtomography system at the Advanced Photon Source

International Nuclear Information System (INIS)

DeCarlo, F.; Foster, I.; Insley, J.; Kesselman, C.; Lane, P.; Mancini, D.; McNulty, I.; Su, M.; Tieman, B.; Wang, Y.; Laszewski, G. von

1999-01-01

The combination of high-brilliance x-ray sources, fast detector systems, wide-bandwidth networks, and parallel computers can substantially reduce the time required to acquire, reconstruct, and visualize high-resolution three-dimensional tomographic datasets. A quasi-realtime computed x-ray microtomography system has been implemented at the 2-BM beamline at the Advanced Photon Source at Argonne National Laboratory. With this system, a complete tomographic data set can be collected in about 15 minutes. Immediately after each projection is obtained, it is rapidly transferred to the Mathematics and Computing Sciences Division where preprocessing and reconstruction calculations are performed concurrently with the data acquisition by a SGI parallel computer. The reconstruction results, once completed, are transferred to a visualization computer that performs the volume rendering calculations. Rendered images of the reconstructed data are available for viewing back at the beamline experiment station minutes after the data acquisition was complete. The fully pipelined data acquisition and reconstruction system also gives us the option to acquire the tomographic data set in several cycles, initially with coarse then with fine angular steps. At present the projections are acquired with a straight-ray projection imaging scheme using 5-20 keV hard x rays in either phase or amplitude contrast mode at a 1-10 pm resolution. In the future, we expect to increase the resolution of the projections to below 100 nm by using a focused x-ray beam at the 2-ID-B beamline and to reduce the combined acquisition and computation time to the 1 min scale with improvements in the detectors, network links, software pipeline, and computation algorithms

Spectral and spatial characteristics of x-ray film/screen combinations up to x-ray energy of 3 MeV

International Nuclear Information System (INIS)

Ginzburg, A.; Carmel, Y.; Segal, Y.; Notea, A.

1986-01-01

The present study is directed towards quantifying some of the parameters which define the quality of the image obtained on x-ray sensitive films and its usual accompanying intensifying screens. Both industrial (Agfa-Geveart D2,D4,D7) and medical (Kodak XAR-5) films with a variety of screens such as metallic (lead) and fluorescent (calcium tungstate, rare earth) were compared. A variety of sources were employed (radioactive, linear accelerators, flash) in order to cover the average x-ray energy spectrum from 100KeV to 3000KeV. This energy spectrum is of interest for non destructive testing, terminal ballistics and for medical purposes. The results indicate that the sensitivity of industrial x-ray films decreases with energy in the range of 100KeV to 1MeV, levels off and increases again with increasing energy. A 2.75MeV Na 24 radioactive source was used to achieve accurate calibration at the high end of the spectrum. Also, the noise level of x-ray industrial films versus film density was found to peak at a density of D=1.4. The line spread function (LSF) - or resolution - of both industrial and medical film/screen combinations were derived from the optical density of a step wedge response on the film. The noise level of medical films is twice as high compared to industrial films and their LSF is 4 to 8 times larger at x-ray energies of 3MeV. Using Pb screens in contact with common industrial x-ray films yields amplification of 2 (compared to a bare film)

Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia.

LENUS (Irish Health Repository)

Houlihan, Diarmaid D

2009-08-21

X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.

Combined analysis of 1,3-benzodioxoles by crystalline sponge X-ray crystallography and laser desorption ionization mass spectrometry.

Science.gov (United States)

Hayashi, Yukako; Ohara, Kazuaki; Taki, Rika; Saeki, Tomomi; Yamaguchi, Kentaro

2018-03-12

The crystalline sponge (CS) method, which employs single-crystal X-ray diffraction to determine the structure of an analyte present as a liquid or an oil and having a low melting point, was used in combination with laser desorption ionization mass spectrometry (LDI-MS). 1,3-Benzodioxole derivatives were encapsulated in CS and their structures were determined by combining X-ray crystallography and MS. After the X-ray analysis, the CS was subjected to imaging mass spectrometry (IMS) with an LDI spiral-time-of-flight mass spectrometer (TOF-MS). The ion detection area matched the microscopic image of the encapsulated CS. In addition, the accumulated 1D mass spectra showed that fragmentation of the guest molecule (hereafter, guest) can be easily visualized without any interference from the fragment ions of CS except for two strong ion peaks derived from the tridentate ligand TPT (2,4,6-tris(4-pyridyl)-1,3,5-triazine) of the CS and its fragment. X-ray analysis clearly showed the presence of the guest as well as the π-π, CH-halogen, and CH-O interactions between the guest and the CS framework. However, some guests remained randomly diffused in the nanopores of CS. In addition, the detection limit was less than sub-pmol order based on the weight and density of CS determined by X-ray analysis. Spectroscopic data, such as UV-vis and NMR, also supported the encapsulation of the guest through the interaction between the guest and CS components. The results denote that the CS-LDI-MS method, which combines CS, X-ray analysis and LDI-MS, is effective for structure determination.

Nondestructive multielement analyses of airborne particulates by combined uses of instrumental neutron activation analysis and energy dispersive X-ray fluorescence analysis

International Nuclear Information System (INIS)

Mamuro, Tetsuo; Matsuda, Yatsuka; Mizohata, Akira

1974-01-01

Combined uses of instrumental neutron activation analysis and energy dispersive X-ray fluorescence analysis make it possible to analyze nondestructively a considerably large number of elements in airborne particulates. We have confirmed that up to 45 elements can be analyzed without any chemical procedures for urban airborne particulate samples. As the radiation spectrometry by semiconductor detectors and the automatic data reduction by electronic computation are quite common to the two techniques, combined uses of them produce no special annoyance. Several elements can be analyzed by both of them and therefore the reliability of the analytical results can be comfirmed by comparing the data obtained by them with each other. It is noted that this confirmation can be made for the very same sample. In this article are described our experiences of multielement analyses of airborne particulates and some problems to be solved in further studies. (auth.)

Central motor and sensory pathway involvement in an X-linked Charcot-Marie-Tooth family.

Science.gov (United States)

Zambelis, T; Panas, M; Kokotis, P; Karadima, G; Kararizou, E; Karandreas, N

2008-06-01

The aim of the present study was to investigate the subclinical involvement of the central nervous system (CNS) in an X-linked Charcot-Marie-Toth (CMTX) family. Seven subjects, all members of one family with a C.462T > G connexin 32 (Cx32) mutation were investigated by Blink reflex, Somatosensory evoked potentials (SEP) and Transcranial magnetic stimulation (TMS). There were five clinically symptomatic for CMT neuropathy (four male and one female) and two asymptomatic (female) subjects. Subclinical CNS involvement was observed in all, symptomatic and asymptomatic subjects. This is the largest CMTX neuropathy family investigated for CNS involvement. Electrophysiological involvement of the CNS in every examined member of this family was observed, raising the question of a more systematic involvement of the CNS in CMTX disease.

The Juberg-Marsidi syndrome maps to the proximal long arm of the X chromosome (Xq12-q21)

Energy Technology Data Exchange (ETDEWEB)

Saugier-Veber, P.; Abadie, V.; Turleau, C.; Munnich, A.; Lyonnet, S. (Hopital des Enfants Malades, Paris (France)); Moncla, A. (Centre de Genetique Medicale, Marseille (France)); Mathieu, M.; Piussan, C.; Mattei, J.F. (Centre Hospitalier et Universitaire, Amiens (France))

1993-06-01

Juberg-Marsidi syndrome (McKusick 309590) is a rare X-linked recessive condition characterized by severe mental retardation, growth failure, sensorineural deafness, and microgenitalism. Here the authors report on the genetic mapping of the Juberg-Marsidi gene to the proximal long arm of the X chromosome (Xq12-q21) by linkage to probe pRX214H1 at the DXS441 locus (Z = 3.24 at [theta] = .00). Multipoint linkage analysis placed the Juberg-Marsidi gene within the interval defined by the DXS159 and the DXYS1X loci in the Xq12-q21 region. These data provide evidence for the genetic distinction between Juberg-Marsidi syndrome and several other X-linked mental retardation syndromes that have hypogonadism and hypogenitalism and that have been localized previously. Finally, the mapping of the Juberg-Marsidi gene is of potential interest for reliable genetic counseling of at-risk women. 25 refs., 2 figs., 3 tabs.

High Precision Ranging and Range-Rate Measurements over Free-Space-Laser Communication Link

Science.gov (United States)

Yang, Guangning; Lu, Wei; Krainak, Michael; Sun, Xiaoli

2016-01-01

We present a high-precision ranging and range-rate measurement system via an optical-ranging or combined ranging-communication link. A complete bench-top optical communication system was built. It included a ground terminal and a space terminal. Ranging and range rate tests were conducted in two configurations. In the communication configuration with 622 data rate, we achieved a two-way range-rate error of 2 microns/s, or a modified Allan deviation of 9 x 10 (exp -15) with 10 second averaging time. Ranging and range-rate as a function of Bit Error Rate of the communication link is reported. They are not sensitive to the link error rate. In the single-frequency amplitude modulation mode, we report a two-way range rate error of 0.8 microns/s, or a modified Allan deviation of 2.6 x 10 (exp -15) with 10 second averaging time. We identified the major noise sources in the current system as the transmitter modulation injected noise and receiver electronics generated noise. A new improved system will be constructed to further improve the system performance for both operating modes.

Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy.

Science.gov (United States)

Muona, Mikko; Ishimura, Ryosuke; Laari, Anni; Ichimura, Yoshinobu; Linnankivi, Tarja; Keski-Filppula, Riikka; Herva, Riitta; Rantala, Heikki; Paetau, Anders; Pöyhönen, Minna; Obata, Miki; Uemura, Takefumi; Karhu, Thomas; Bizen, Norihisa; Takebayashi, Hirohide; McKee, Shane; Parker, Michael J; Akawi, Nadia; McRae, Jeremy; Hurles, Matthew E; Kuismin, Outi; Kurki, Mitja I; Anttonen, Anna-Kaisa; Tanaka, Keiji; Palotie, Aarno; Waguri, Satoshi; Lehesjoki, Anna-Elina; Komatsu, Masaaki

2016-09-01

The ubiquitin fold modifier 1 (UFM1) cascade is a recently identified evolutionarily conserved ubiquitin-like modification system whose function and link to human disease have remained largely uncharacterized. By using exome sequencing in Finnish individuals with severe epileptic syndromes, we identified pathogenic compound heterozygous variants in UBA5, encoding an activating enzyme for UFM1, in two unrelated families. Two additional individuals with biallelic UBA5 variants were identified from the UK-based Deciphering Developmental Disorders study and one from the Northern Finland Intellectual Disability cohort. The affected individuals (n = 9) presented in early infancy with severe irritability, followed by dystonia and stagnation of development. Furthermore, the majority of individuals display postnatal microcephaly and epilepsy and develop spasticity. The affected individuals were compound heterozygous for a missense substitution, c.1111G>A (p.Ala371Thr; allele frequency of 0.28% in Europeans), and a nonsense variant or c.164G>A that encodes an amino acid substitution p.Arg55His, but also affects splicing by facilitating exon 2 skipping, thus also being in effect a loss-of-function allele. Using an in vitro thioester formation assay and cellular analyses, we show that the p.Ala371Thr variant is hypomorphic with attenuated ability to transfer the activated UFM1 to UFC1. Finally, we show that the CNS-specific knockout of Ufm1 in mice causes neonatal death accompanied by microcephaly and apoptosis in specific neurons, further suggesting that the UFM1 system is essential for CNS development and function. Taken together, our data imply that the combination of a hypomorphic p.Ala371Thr variant in trans with a loss-of-function allele in UBA5 underlies a severe infantile-onset encephalopathy. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Crystallization Kinetics of Nanocrystalline Materials by Combined X-ray Diffraction and Differential Scanning Calorimetry Experiments

Czech Academy of Sciences Publication Activity Database

Gil-González, E.; Perejón, A.; Sánchez-Jiménez, P. E.; Medina-Carrasco, S.; Kupčík, Jaroslav; Šubrt, Jan; Criado, J. M.; Pérez-Maqueda, L. A.

2018-01-01

Roč. 18, č. 5 (2018), s. 3107-3116 ISSN 1528-7483 Institutional support: RVO:61388980 Keywords : nanocrysalline alloys * combined X ray diffraction * crystallization kinetics Subject RIV: CA - Inorganic Chemistry OBOR OECD: Inorganic and nuclear chemistry Impact factor: 4.055, year: 2016

Linking air and water transport in intact soils to macropore characteristics inferred from X-ray computed tomography

DEFF Research Database (Denmark)

Katuwal, S.; Nørgaard, Trine; Møldrup, Per

2015-01-01

Soil macropores often control fluid flow and solute transport, and quantification of macropore characteristics including their variability in space and time are essential to predict soil hydraulic and hydrogeochemical functions. In this study, measurements of air and solute transport properties...... and direct macropore visualization by X-ray CT scanning were carried out on 17 large (19-cm diam.; 20-cm length) undisturbed soil columns sampled across a field site (Silstrup, Denmark) with natural gradients in texture and density. Air permeability (ka) at in-situ water content and -20 hPa of matric......-porosity, suggesting that density is the main control of functional soil structure and gas and solute transport at the Silstrup site. Linking gas transport and chemical tracer experiments with X-ray CT based visualization and quantification of macro-porosity was found to be a powerful method to understand field scale...

Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-fluorouracil or ftorafur and x rays

International Nuclear Information System (INIS)

Byfield, J.E.; Calabro-Jones, P.; Klisak, I.; Kulhanian, F.

1982-01-01

The combined effects of X ray and 5-fluorouracil (5-FU) in tissue culture have been studied using two human adenocarcinoma lines (HeLa and HT-29 cells). Both showed similar sensitivities to 5-FU, HeLa cells appearing somewhat more resistant to higher concentrations. Combined treatment of both cell types with 5-FU and X rays led to a time-dependent enhancement of cell killing (''radiosensitization''). Only post-radiation incubation had any effect, prior exposure to 5-FU being strictly additive. Enhanced cell killing by combined 5-FU and X rays could not be explained by either the infliction of additional acute damage in the immediate post-radiation period or an inhibitory effect of 5-FU on the repair of sub-lethal X ray injury. Rather, the enhanced cytotoxicity proved to be dependent on a damage expressed in time periods exceeding the duration of a cell doubling time in vitro. Overall, the data equally suggest that X rays may sensitize the cells to 5-FU. The enhanced cell killing is maximized if the cells are continuously exposed to 5-FU for 48 hours following the X ray exposure. These results indicate that clinical treatment regimens might be useful in evaluating 5-FU infusional scheduling in accordance with these unique requirements, which are not met by conventional bolus 5-FU and X ray therapy fractionation regimens. Ftorafur, a drug proposed to act as a slow release form of 5-FU, was found to show limited cytotoxic potential in vitro and did not significantly enhance cell killing after X ray exposure

Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB).

Science.gov (United States)

Berger, W; van Duijnhoven, G; Pinckers, A; Smits, A; Ropers, H H; Cremers, F

1995-01-01

Linkage analysis has been performed in a large Dutch pedigree with X-linked recessive congenital stationary night blindness (CSNB) by utilizing 16 DNA markers from the proximal short arm of the human X chromosome (Xp21.1-11.2). Thirteen polymorphic markers are at least partially informative and have enabled pairwise and multipoint linkage analysis. For three loci, i.e. DXS228, the monoamine oxidase B gene and the Norrie disease gene (NDG), multipoint linkage studies have yielded maximum lod scores of > 3.0 at a recombination fraction of zero. Analysis of recombination events has enabled us to rule out the possibility that the underlying defect in this family is allelic to RP3; the gene defect could also be excluded from the proximal part of the region known to carry RP2. Linkage data are consistent with a possible involvement of the NDG but mutations in the open reading frame of this gene have not been found.

Origination of an X-linked testes chimeric gene by illegitimate recombination in Drosophila.

Directory of Open Access Journals (Sweden)

J Roman Arguello

2006-05-01

Full Text Available The formation of chimeric gene structures provides important routes by which novel proteins and functions are introduced into genomes. Signatures of these events have been identified in organisms from wide phylogenic distributions. However, the ability to characterize the early phases of these evolutionary processes has been difficult due to the ancient age of the genes or to the limitations of strictly computational approaches. While examples involving retrotransposition exist, our understanding of chimeric genes originating via illegitimate recombination is limited to speculations based on ancient genes or transfection experiments. Here we report a case of a young chimeric gene that has originated by illegitimate recombination in Drosophila. This gene was created within the last 2-3 million years, prior to the speciation of Drosophila simulans, Drosophila sechellia, and Drosophila mauritiana. The duplication, which involved the Bällchen gene on Chromosome 3R, was partial, removing substantial 3' coding sequence. Subsequent to the duplication onto the X chromosome, intergenic sequence was recruited into the protein-coding region creating a chimeric peptide with approximately 33 new amino acid residues. In addition, a novel intron-containing 5' UTR and novel 3' UTR evolved. We further found that this new X-linked gene has evolved testes-specific expression. Following speciation of the D. simulans complex, this novel gene evolved lineage-specifically with evidence for positive selection acting along the D. simulans branch.

Lymphoid nodular hyperplasia in a patient with severe combined immunodeficiency disease

International Nuclear Information System (INIS)

Sanchez-Alegre, M. L.; Casanova, A.; Delgado, J.; Relanzon, S.

2001-01-01

We describe a case of lymphoid nodular hyperplasia in a woman with severe combined immunodeficiency disease. the patient complained of constipation and episodes of abdominal pain, and examination revealed the presence of a large abdominal mass. The diagnosis was suspected on the basis of the initial radiological studies, but intestinal biopsy was necessary to rule out lymphomatous involvement. We point out the radiological features of this entity which, despite the fact that it may be a chance finding of no pathological significance, requires special attention, especially in immuno deficient individuals. (Author) 10 refs

Animal model of atherosclerosis using rabbit experimentally induced by combination of X-ray and hypercholesterolemia

International Nuclear Information System (INIS)

Ishiyama, Tomotoshi; Sawai, Takashi; Okuma, Tsuneo; Mori, Shozo

1995-01-01

An attempt was made to prepare an animal model of atherosclerosis similar to human lesions. The experimental animals were male Japanese white rabbits weighting about 2 kg. Hypercholesterolemia was experimentally induced by giving a 1% cholesterol diet. Four weeks later, a single dose of 45 Gy was delivered to the femur to produce vascular changes. Soon after irradiation, immunohistochemical examination revealed the adhesion and invasion of macrophages to endothelial cells, followed by accumulation of foam cells and thickness of the intimal plaques. Three months after irradiation, these thickened plaques became fibrotic, calcified, and necrotic. The tunica media was thinned and the internal elastic lamella was destroyed. Irradiated arteries exhibited not only severe narrowing of the lumen but also aneurysmal dilation and the lesions of the irradiated arteries resembled human atherosclerosis. In conclusion, the atherosclerotic model produced by combining experimental hypercholesterolemia and X-ray irradiaiton may serve as a useful model for studies on atherosclerosis because it can be prepared with no need of complicated or time-consuming procedures. (N.K.)

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family

Directory of Open Access Journals (Sweden)

Galantuomo MS

2016-11-01

Full Text Available Maria Silvana Galantuomo,1,* Maurizio Fossarello,1 Alberto Cuccu,1 Roberta Farci,1 Markus N Preising,2 Birgit Lorenz,2 Pietro Emanuele Napoli1,* 1Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy; 2Department of Ophthalmology, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany *These authors contributed equally to this work Background: Juvenile X-linked retinoschisis (RS1, OMIM: 312700 is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments. Purpose: The purposes of this study were to present, for the first time, a p.Arg197Cys missense mutation in the RS1 gene (OMIM: 300839 in a four-generation Italian family with RS1 and to examine the clinical response to the treatment with acetazolamide tablets alone or in combination with dorzolamide eye drops as assessed by spectral-domain optical coherence tomography (SD-OCT. Methods: Eleven individuals, including two brothers with RS1 (patients 1 and 2, underwent a full medical history examination and a comprehensive ocular assessment that involved SD-OCT, fluorescein angiography, electroretinography and DNA analysis. Each RS1 patient received oral acetazolamide (375 mg daily during the first three months. Thereafter, patient 1 continued only with dorzolamide eyedrops three times a day for a period of three months, while patient 2 spontaneously stopped both medications. Results: Sequence analysis of the RS1 gene identified a hemizygous c.589C>T (p.Arg197Cys missense mutation in exon 6, which has not been previously reported in an Italian family. A different response to the medical therapy was observed in the four eyes of the two affected brothers hemizygous for

Synergistic effect of factor VII gene polymorphisms causing mild factor VII deficiency in a case of severe factor X deficiency.

Science.gov (United States)

Deshpande, Rutuja; Ghosh, Kanjaksha; Shetty, Shrimati

2017-01-01

Congenital combined deficiency of coagulation factors VII and X are mainly attributed to large deletions involving both the genes in chromosome 13 or occasionally due to the coincidental occurrence of independently occurring mutations. We report the molecular basis of congenital combined deficiency of factors VII and X in a 6-year-old female child. Direct DNA sequencing of both factor VII (F7) and factor X (F10) genes showed a novel homozygous missense mutation p.Cys90Tyr (c.307G>A) in exon 4 of F10. No mutations were detected in F7; however, the patient was homozygous for three polymorphic alleles known to be associated with reduced factor VII levels. The present case illustrates the synergistic effect of multiple polymorphisms resulting in phenotypic factor VII deficiency in the absence of a pathogenic mutation.