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41.
A 50-kDa membrane protein mediates sialic acid-independent binding and infection of conjunctival cells by adenovirus type 37 总被引:6,自引:0,他引:6
The ocular tropism of adenovirus type 37 (Ad37) does not correlate with the wide distribution of the 46-kDa coxsackievirus and adenovirus receptor (CAR), the major receptor for most adenovirus serotypes. We previously found that Ad37 infects and binds well to conjunctival cells (Chang C), but poorly to lung epithelial (A549) cells that express CAR and hypothesized that this serotype uses a distinct receptor that is selectively expressed on conjunctival cells. To test this, we produced particles of a fiber-deleted Ad5 vector containing the Ad37 fiber protein. The "pseudotyped" vector infected Chang C cells better than A549 cells using a CAR-independent pathway. Ad37 binding was calcium-dependent and was abolished by protease digestion of cell surface proteins. Using a virus overlay protein blot assay (VOPBA), we detected calcium-dependent Ad37 binding to 50- and 60-kDa membrane proteins on permissive Chang C cells. In contrast, calcium-dependent binding was detected with only the 60-kDa protein on nonpermissive A549 cells. Ad19p, a closely related serotype that failed to bind to conjunctival cells, recognized the 60-kDa, but not the 50-kDa, protein. Ad37 has been reported to use sialic acid instead of CAR as a cell receptor on A549 cells. Pretreatment of Chang C cells with neuraminidase abolished Ad37 binding to only the 60-kDa protein, suggesting that sialic acid mediates Ad37 binding to the 60-kDa protein. The pseudotyped Ad37 vector was also able to infect neuraminidase-treated Chang C cells. Thus, subgroup D adenoviral binding to the 50-kDa protein is calcium-dependent and cell type- and serotype-specific, whereas binding to the 60-kDa protein is not necessary for infection of conjunctival cells. Together, these data suggest that the 50-kDa protein is the major receptor for Ad37 on conjunctival cells. 相似文献
42.
43.
GD Cramer DJ Allen LJA DiDio W Potvin R Brinker 《Surgical and radiologic anatomy : SRA》1990,12(4):287-290
Summary Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for normal subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm3, while that for males was 16.3 cm3 and that for females was 18.0 cm3. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.
Evaluation du volume des ventricules cérébraux à partir des images obtenues en résonance magnétique nucléaire chez 38 sujets humains
Résumé La détermination exacte du volume des ventricules cérébraux est importante en clinique comme par exemple dans la démence présénile d'Alzheimer, la schizophrénie et l'hypertension intracrânienne bénigne. Des études antérieures ont étudié la fiabilité de la résonance magnétique nucléaire en pratique clinique pour évaluer le volume des ventricules cérébraux. Toutefois une évaluation correcte dans les conditions pathologiques implique une bonne connaissance des données morphométriques du sujet normal. Pour établir ces données sur « le sujet normal », nous avons étudié les coupes obtenues en IRM chez 38 sujets apparemment indemnes de toute pathologie; nous avons calculé le volume ventriculaire dans chaque cas en utilisant des méthodes mises au point auparavant dans notre laboratoire. Les résultats ont été ensuite comparés avec ceux obtenus par d'autres études utilisant soit des moules ventriculaires, soit des coupes tomographiques computérisées. Le volume ventriculaire total moyen chez 38 sujets est de 17,4 cm3, mais il est chez les sujets masculins de 16,3 cm3 et chez les sujets de sexe féminin de 18 cm3. Une corrélation faible mais significative a été trouvée entre l'âge du sujet et le volume ventriculaire, étant entendu que la taille du ventricule augmente avec l'âge.相似文献
44.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
45.
Mahadevaiah SK; Odorisio T; Elliott DJ; Rattigan A; Szot M; Laval SH; Washburn LL; McCarrey JR; Cattanach BM; Lovell-Badge R; Burgoyne PS 《Human molecular genetics》1998,7(4):715-727
An RNA-binding motif (RBM) gene family has been identified on the human Y
chromosome that maps to the same deletion interval as the 'azoospermia
factor' (AZF). We have identified the homologous gene family (Rbm) on the
mouse Y with a view to investigating the proposal that this gene family
plays a role in spermatogenesis. At least 25 and probably >50 copies of
Rbm are present on the mouse Y chromosome short arm located between Sry and
the centromere. As in the human, a role in spermatogenesis is indicated by
a germ cell-specific pattern of expression in the testis, but there are
distinct differences in the pattern of expression between the two species.
Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are
female due to a position effect resulting in non-expression of Sry ;
sex-reversing such mice with an Sry transgene produces males with a high
incidence of abnormal sperm, making this the third deletion interval on the
mouse Y that affects some aspect of spermatogenesis. Most of the copies of
Rbm map to this deletion interval, and the Yd1males have markedly reduced
Rbm expression, suggesting that RBM deficiency may be responsible for, or
contribute to, the abnormal sperm development. In man, deletion of the
functional copies of RBM is associated with meiotic arrest rather than
sperm anomalies; however, the different effects of deletion are consistent
with the differences in expression between the two species.
相似文献
46.
ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome 总被引:11,自引:3,他引:11
Picketts DJ; Higgs DR; Bachoo S; Blake DJ; Quarrell OW; Gibbons RJ 《Human molecular genetics》1996,5(12):1899-1907
It was shown recently that mutations of the ATRX gene give rise to a
severe, X-linked form of syndromal mental retardation associated with alpha
thalassaemia (ATR-X syndrome). In this study, we have characterised the
full-length cDNA and predicted structure of the ATRX protein. Comparative
analysis shows that it is an entirely new member of the SNF2 subgroup of a
superfamily of proteins with similar ATPase and helicase domains. ATRX
probably acts as a regulator of gene expression. Definition of its genomic
structure enabled us to identify four novel splicing defects by screening
52 affected individuals. Correlation between these and previously
identified mutations with variations in the ATR-X phenotype provides
insights into the pathophysiology of this disease and the normal role of
the ATRX protein in vivo.
相似文献
47.
48.
S I Firshein L W Hoyer J Lazarchick B G Forget J C Hobbins L P Clyne F A Pitlick W A Muir I R Merkatz M J Mahoney 《The New England journal of medicine》1979,300(17):937-941
Prenatal diagnosis of classic hemophilia (hemophilia A) in mid-trimester was achieved by means of immunoradiometric assays for factor VIII on fetal plasma and amniotic-fluid mixtures obtained by fetoscopy. Samples were analyzed from six male fetuses at risk for severe hemophilia and from nine control fetuses for which fetoscopy was carried out to attempt prenatal diagnosis of other genetic disorders. The factor VIII coagulant-antigen values for the control (non-hemophilic) samples were 17 to 94, and the factor VIII related-antigen concentrations were 50 to 155 U per deciliter. Three of the fetuses at risk for hemophilia had factor VIII values in the control range, and these infants were normal at birth. The other three fetuses had low concentrations of factor VIII coagulant antigen but normal concentrations of factor VIII related antigen. These values and the diagnoses of severe hemophilia were confirmed with blood from the abortuses. 相似文献
49.
Loveland KA Stehbens JA Mahoney EM Sirois PA Nichols S Bordeaux JD Watkins JM Amodei N Hill SD Donfield S 《Journal of pediatric psychology》2000,25(5):309-322
OBJECTIVE: To determine whether declines in immune functioning are associated with changes in neuropsychological performance in children and adolescents with hemophilia who are infected with the human immunodeficiency virus (HIV). METHODS: Participants were 333 males with hemophilia, ages 6-19 years at entry. A baseline and four annual neuropsychological evaluations were given. A longitudinal growth curves analysis of data was performed to detect changes associated with declining immune function. The cohort was stratified into four groups: (1) HIV- (n = 126); (2) HIV+, average of first two and last two CD4 counts > or = 200, (n = 106; High CD4 group); (3) HIV+, average first two counts > or = 200, average last two counts < 200 (n = 41; CD4 Drop group); and (4) HIV+, average first two and last two counts < 200 (n = 60; Low CD4 group). RESULTS: There were significant differences among the four groups over time in nonverbal intelligence, perceptual/performance skills, nonverbal memory, academic achievement, and language. The Low CD4 group consistently showed the greatest decrement in performance. On measures showing a practice effect for repeated measurements, the Low CD4 group participants' scores remained stable over time, suggesting opposing effects of practice and HIV-related declines. Lowered academic performance relative to IQ was found in all groups. CONCLUSIONS: Declines in neuropsychological functioning are directly related to declines in immune functioning in HIV+ children, adolescents, and young adults with hemophilia. Hemophilia itself may be a risk factor for academic underachievement. 相似文献
50.
The formation of covalent isopeptide cross-links between cell surface protein molecules by the enzyme transglutaminase C influences cell adhesion and morphology. Retinoid-inducible cross-linking activity associated with this enzyme is present in the developing rat cerebellar cortex [Perry M. J. M. et al. (1995) Neuroscience 65, 1063-1076]. A monoclonal antibody was used to localize transglutaminase C to granule neurons in the developing cerebellar cortex. The enzyme was inducible by retinoic acid both in granule neurons cultured from postnatal rat cerebellar cortex and in cells of the embryonic dorsal rhombic lip, which contain granule neuron precursors. A possible biological function for transglutaminase activity was investigated in living granule neurons, cultured on a biomatrix substratum, studied by time-lapse cinematographic analysis using the transglutaminase inactivator RS-48373-007. Inhibition of cross-linking activity did not influence the number of neurites formed by granule neurons, but caused the destabilization of neurites during the initial outgrowth period, seen as an increase in the number of growth cone retractions and the onset of premature axon collateral formation (bifurcation). Inactivation of cross-linking activity prevented the formation of fascicles between neurites only when cells were cultured on a biomatrix surface. Two glial proteins involved in cell-extracellular matrix interactions, midkine and galectin-3, were identified as putative substrates for granule neuron transglutaminase.The results suggest that covalent cross-link formation by transglutaminase C or a related enzyme generates multimeric molecular forms of glial-derived proteins, and plays a role in stabilizing newly formed neurites. A possible non-pathological role for transglutaminase in the control of axon collateral branching by developing granule neurons in the cerebellar cortex is discussed. 相似文献