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41.
Spectrum of NSD1 mutations in Sotos and Weaver syndromes 总被引:8,自引:0,他引:8
Rio M Clech L Amiel J Faivre L Lyonnet S Le Merrer M Odent S Lacombe D Edery P Brauner R Raoul O Gosset P Prieur M Vekemans M Munnich A Colleaux L Cormier-Daire V 《Journal of medical genetics》2003,40(6):436-440
Interestingly, mental retardation was consistently more severe in patients with NSD1 deletions. Macrocephaly and facial gestalt but not overgrowth and advanced bone age were consistently observed in Sotos syndrome patients. We suggest therefore considering macrocephaly and facial gestalt as mandatory criteria for the diagnosis of Sotos syndrome and overgrowth and advanced bone age as minor criteria. 相似文献
42.
Mannoprotein from Cryptococcus neoformans promotes T-helper type 1 anticandidal responses in mice
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Pietrella D Mazzolla R Lupo P Pitzurra L Gomez MJ Cherniak R Vecchiarelli A 《Infection and immunity》2002,70(12):6621-6627
We previously demonstrated that mannoprotein (MP) from Cryptococcus neoformans (CnMP) stimulates interleukin-12 production by human monocytes, thus fostering a T-helper type 1 (Th1) protective anticryptococcal response. In this paper we show that CnMP was also able to induce a Candida albicans-directed protective Th1 response. This was demonstrated for mice immunized with CnMP by induction of a delayed-type hypersensitivity (DTH) reaction to C. albicans MP (CaMP) as well as induction of gamma interferon production by CD4(+) and CD8(+) splenic T cells stimulated in vitro with CaMP. CnMP-immunized mice were also partially protected from lethal systemic challenge with C. albicans, as shown by prolonged median survival times and decreased fungal burden in the kidney. Much evidence supports the validity of these cross-reactive and functional Th1 responses: (i) a non-cross-reactive C. albicans antigen, such as enolase, did not produce a DTH response to CaMP; (ii) passive adoptive transfer of T cells primed with CnMP induced a DTH reaction; (iii) C. neoformans extract elicited a DTH response to CaMP; and (iv) a monoclonal antibody (7H6) directed against a major and immunodominant T-cell-stimulatory 65-kDa MP (MP65) of C. albicans also recognized discrete 100-kDa constituents of C. neoformans extracts, as well as secretory constituents of the fungus. These results suggest the presence of common Th1 antigenic determinants in the mannoproteic material of C. neoformans and C. albicans epitopes, which should be considered in devising common strategies for immunoprophylactic or immunotherapeutic control of the fungi. 相似文献
43.
Synthesis of melanin-like pigments by Sporothrix schenckii in vitro and during mammalian infection
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Morris-Jones R Youngchim S Gomez BL Aisen P Hay RJ Nosanchuk JD Casadevall A Hamilton AJ 《Infection and immunity》2003,71(7):4026-4033
Melanin has been implicated in the pathogenesis of several important human fungal pathogens. Existing data suggest that the conidia of the dimorphic fungal pathogen Sporothrix schenckii produce melanin or melanin-like compounds; in this study we aimed to confirm this suggestion and to demonstrate in vitro and in vivo production of melanin by yeast cells. S. schenckii grown on Mycosel agar produced visibly pigmented conidia, although yeast cells grown in brain heart infusion and minimal medium broth appeared to be nonpigmented macroscopically. However, treatment of both conidia and yeast cells with proteolytic enzymes, denaturant, and concentrated hot acid yielded dark particles similar in shape and size to the corresponding propagules, which were stable free radicals consistent with identification as melanins. Melanin particles extracted from S. schenckii yeast cells were used to produce a panel of murine monoclonal antibodies (MAbs) which labeled pigmented conidia, yeast cells, and the isolated particles. Tissue from hamster testicles infected with S. schenckii contained fungal cells that were labeled by melanin-binding MAbs, and digestion of infected hamster tissue yielded dark particles that were also reactive. Additionally, sera from humans with sporotrichosis contained antibodies that bound melanin particles. These findings indicate that S. schenckii conidia and yeast cells can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role in the pathogenesis of sporotrichosis. 相似文献
44.
Automated fluorescent genotyping detects 10% of cryptic subtelomeric rearrangements in idiopathic syndromic mental retardation 总被引:2,自引:1,他引:2
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Rio M Molinari F Heuertz S Ozilou C Gosset P Raoul O Cormier-Daire V Amiel J Lyonnet S Le Merrer M Turleau C de Blois MC Prieur M Romana S Vekemans M Munnich A Colleaux L 《Journal of medical genetics》2002,39(4):266-270
Recent studies have shown that cryptic unbalanced subtelomeric rearrangements contribute to a significant proportion of idiopathic syndromic mental retardation cases. Using a fluorescent genotyping based strategy, we found a 10% rate of cryptic subtelomeric rearrangements in a large series of 150 probands with severe idiopathic syndromic mental retardation and normal RHG-GTG banded karyotype. Fourteen children were found to carry deletions or duplications of one or more chromosome telomeres and two children had uniparental disomy. This study clearly shows that fluorescent genotyping is a sensitive and cost effective method that not only detects cryptic subtelomeric rearrangements but also provides a unique opportunity to detect uniparental disomies. We suggest giving consideration to systematic examination of subtelomeric regions in the diagnostic work up of patients with unexplained syndromic mental retardation. 相似文献
45.
The medial nucleus of the amygdala (Me) processes both chemosensory and hormonal input. In the male Syrian hamster the integrity of this nucleus is essential for normal reproductive behavior. To determine if gonadal steroids modulate neuronal structure in this nucleus, the morphology of Golgi-stained neurons in the anterior and posterior regions of Me were compared in castrated and reproductively intact adult hamsters. In castrated males, neurons in the posterior, but not the anterior, region of Me undergo structural changes, as indicated by a decrease in the mean highest dendritic branch level and mean somal area compared to intact males. To further elucidate the importance of testosterone and its metabolites in maintenance of neuronal structure in the adult, seven groups of male Syrian hamsters were studied. Animals were castrated and received a blank silastic capsule or a capsule filled with either testosterone, dihydrotestosterone, or estradiol, or two capsules containing both metabolites, dihydrotestosterone and estradiol. Two groups of reproductively intact animals were included: brains from one group were processed simultaneously with the castrated and hormone-treated groups (control intact group), and the other group was processed at the beginning of the experiment. Animals were tested for mating behavior and flank glands were measured to test whether the capsules were effective in releasing the hormones into circulation. After a 12-week survival period, the brains were processed with Golgi stain and well-impregnated neurons from the posterior Me were quantitatively analyzed for somal area, highest dendritic branch, total dendritic length, and density of spines. All the measures analyzed revealed a consistent pattern of response to the different gonadal steroids. Castration resulted in a decrease in the mean somal area, the mean highest dendritic branch, and the percentage of neurons with tertiary branch segments. Dihydrotestosterone treatment also resulted in a significant decrease in somal area, mean highest dendritic branch, and percentage of neurons with tertiary dendritic branches. In addition, the total dendritic length and spine density on terminal dendrites were reduced in these brains. The remaining hormone treatment groups were not significantly different from the control group. These results suggest that in orchidectomized male Syrian hamsters, testosterone or its aromatized form, estradiol, but not dihydrotestosterone, is sufficient to maintain the normal morphology of the neurons in the posterior part of the medial nucleus of the amygdala. 相似文献
46.
47.
HLA-DRB1*1602 allele is positively associated with HPV cervical infection in Bolivian Andean women 总被引:3,自引:0,他引:3
Cervantes J Lema C Valentina Hurtado L Andrade R Hurtado Gomez L Torrico L Zegarra L Quiroga G Asturizaga D Dulon A Prada R Panoso W Yashiki S Fujiyoshi T Sonoda S 《Human immunology》2003,64(9):890-895
Incidence of cervical cancer is high among Bolivian Andean women. Human papillomavirus (HPV) infection is known as the major risk factor of cervical cancer. The host immune system plays an important role in the outcome of HPV infection and associated malignancies. In order to study the immunogenetic background of Bolivian Andean women with regard to HPV infection status, we compared HLA class I and class II allele frequencies between 37 HPV positive and 68 HPV negative Bolivian women. Demographic variables, including distribution of Andean ethnicities, were similar in both groups. Comparison of HLA class I allele frequencies between both groups indicated no significant difference. In contrast, HLA class II DRB1*1602 allele, an Amerindian allele, was significantly higher in the HPV positive women compared with HPV negative controls (chi(2) = 5.2, p < 0.05, odds ratio = 3.17; 95% confidence interval = 1.4-8.8). HPV types present in the HPV positive group were HPV-18, -16, -31, -33, and -58. These results suggest that HLA class II DRB1*1602 may confer susceptibility to infection with genetically related HPV types. This is the first report of an HLA class II association with HPV infection in an Andean population. 相似文献
48.
PTEN mutations in endometrial carcinomas: a molecular and clinicopathologic analysis of 38 cases 总被引:23,自引:0,他引:23
PTEN mutations have been reported to be frequent in endometrioid carinomas of the endometrium (EEC). Some correlation has been found between PTEN mutations and the presence of microsatellite instability (MI) in EEC, but no convincing cause-effect relationship for such association has been offered. DNA of 38 patients with endometrial carcinoma (EC) was extracted from blood and from fresh-frozen and paraffin-embedded tumor tissue. PTEN mutations were detected by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Results were correlated with MI status and clinicopathologic data. PTEN mutations were detected in 17 tumors (44.7%), and they were more frequent in endometrioid (EEC) (17 of 33, 51.5%) than in nonendometrioid carcinomas (NEEC) (0 of 5, 0%). PTEN mutational spectrum differed between MI+ and MItumors. PTEN mutations were detected in 9 of 15 MI+ tumors (60%), but in only 8 of 23 MI- neoplasms (34.8%). In EC with MI, PTEN mutations were detected in short coding mononucleotide repeats (A)s and (A)6 in 4 of 9 carcinomas (44.4%). These results confirm that PTEN is an important target gene in endometrial carcinogenesis. The occurrence of PTEN mutations in short coding mononucleotide repeats in MI-positive tumors suggests that these mutations may be secondary to deficiencies in mismatch repair and gives some explanation for the frequent presence of PTEN mutations in these tumors. 相似文献
49.
Espinosa LE Li Z Gomez Barreto D Calderon Jaimes E Rodriguez RS Sakota V Facklam RR Beall B 《Journal of clinical microbiology》2003,41(1):373-378
To examine the type distribution of pathogenic group A streptococcal (GAS) strains in Mexico, we determined the emm types of 423 GAS isolates collected from ill patients residing in Mexico (Durango or Mexico City). These included 282 throat isolates and 107 isolates from normally sterile sites. Of the other isolates, 38 were recovered from other miscellaneous infections. A total of 31 different emm types were found, revealing a broad overlap between commonly occurring emm types in Mexico and the United States. The information obtained in this study is consistent with the possibility that multivalent, M type-specific vaccines prepared for GAS strain distribution within the United States could theoretically protect against the majority of GAS strains causing disease in the two cities surveyed in Mexico. 相似文献
50.
Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features 总被引:24,自引:2,他引:24
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Shaw-Smith C Redon R Rickman L Rio M Willatt L Fiegler H Firth H Sanlaville D Winter R Colleaux L Bobrow M Carter NP 《Journal of medical genetics》2004,41(4):241-248
The underlying causes of learning disability and dysmorphic features in many patients remain unidentified despite extensive investigation. Routine karyotype analysis is not sensitive enough to detect subtle chromosome rearrangements (less than 5 Mb). The presence of subtle DNA copy number changes was investigated by array-CGH in 50 patients with learning disability and dysmorphism, employing a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Twelve copy number abnormalities were identified in 12 patients (24% of the total): seven deletions (six apparently de novo and one inherited from a phenotypically normal parent) and five duplications (one de novo and four inherited from phenotypically normal parents). Altered segments ranged in size from those involving a single clone to regions as large as 14 Mb. No recurrent deletion or duplication was identified within this cohort of patients. On the basis of these results, we anticipate that array-CGH will become a routine method of genome-wide screening for imbalanced rearrangements in children with learning disability. 相似文献