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排序方式: 共有458条查询结果,搜索用时 15 毫秒
1.
Veronique Braud E. Yvonne Jones Andrew McMichael 《European journal of immunology》1997,27(5):1164-1169
Human histocompatibility leukocyte antigen E (HLA-E) and mouse major histocompatibility complex (MHC) class Ib antigen, Qa-1, share the same substitutions at two normally conserved positions 143 and 147, which are likely to affect binding of the C terminus of peptides. Qa-1 is able to bind a peptide derived from the leader sequence of H-2 D and H-2 L molecules. We developed a peptide binding assay in vitro to compare the binding specificity of HLA-E with the mouse MHC class Ib molecule Qa-1. We demonstrate that HLA-E binds, although poorly, the peptide which binds to Qa-1 and that it also binds nonamer signal sequence-derived peptides from human MHC class I molecules. Using alanine and glycine substitutions, we could define primary anchor residues at positions 2 and 9 and secondary anchor residues at position 7 and possibly 3. 相似文献
2.
3.
P Pfitzenmeyer P Foucher F Piard B Coudert M L Braud P Gabez S Lacroix J P Mabille P Camus 《Thorax》1992,47(8):622-627
BACKGROUND: Nilutamide is a new, specific synthetic antiandrogen, released in several countries for the treatment of metastatic carcinoma of the prostate. Eight patients at the University Medical Centre at Dijon and affiliated referring hospitals developed reversible pulmonary opacities and respiratory symptoms while taking the drug. METHODS: Records of eight patients who developed new, otherwise unexplained chest opacities while taking nilutamide were reviewed. In each patient a careful aetiological search was made for other environmental or endogenous causes. Six patients underwent bronchoalveolar lavage, and lavage fluid was cultured. Corticosteroids were not given, unless gas exchange was compromised (two patients). RESULTS: The eight patients (all male) had had carcinoma of the prostate diagnosed on average 10.2 months earlier. All had improved with nilutamide, with a dramatic decrease of prostate specific antigen levels. Seven had received nilutamide at the recommended dosage of 150 mg/day, and one had received twice that amount. Treatment had lasted on average 113 (range 10-225) days, and the mean cumulated exposure was 21.8 (3-38) grams. The chest radiographs showed bilateral infiltrates, with no consistent topographic predilection. A restrictive lung defect was present in six patients and hypoxia in all (mean arterial oxygen tension (PaO2) 6.6 kPa). Bronchoalveolar lavage showed lymphocytosis in four patients and neutrophilia in two. The outcome was favourable in all patients after they had stopped nilutamide only (five patients), with corticosteroids (two patients) or a simple reduction of nilutamide from 300 to 150 mg/day (one patient). Recovery was associated with improvement of pulmonary function and PaO2. CONCLUSION: Nilutamide is associated with interstitial pneumonitis in about 1% of patients and appears reversible. 相似文献
4.
Liu JQ; Bai XF; Shi FD; Xiao BG; Li HL; Levi M; Mustafa M; Wahren B; Link H 《International immunology》1998,10(8):1139-1148
Induction of mucosal tolerance by inhalation of soluble peptides with
defined T cell epitopes is receiving much attention as a means of
specifically down-regulating pathogenic T cell reactivities in autoimmune
and allergic disorders. Experimental autoimmune encephalomyelitis (EAE)
induced in the Lewis rat by immunization with myelin basic protein (MBP)
and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the
MBP amino acid sequences 68-86 and 87-99. To further define the principles
of nasal tolerance induction, we generated three different MBP peptides
(MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and
evaluated whether their nasal administration on day -11, -10, -9, -8 and -7
prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection
to Lewis rat EAE. Protection was achieved with the encephalitogenic
peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP
110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete
protection to gp-MBP-induced EAE. In contrast, nasal administration of a
mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even
at lower dosage compared to that being used for individual peptides. Rats
tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses
to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays.
Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive
IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node
cells compared to rats receiving MBP 110-128 nasally, while similar low
levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA
expressing cells were observed in the two groups. Nasal administration of
MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord
homogenate-induced EAE, and passive transfer of spleen mononuclear cells
from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE.
Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse
ongoing EAE induced with gp-MBP, although higher doses are required
compared to the dosage needed for prevention. In conclusion, nasal
administration of encephalitogenic MBP peptides can induce antigen-specific
T cell tolerance and confer incomplete protection to gp-MBP-induced EAE,
and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms
are proposed to be responsible for tolerance development after nasal
peptide administration.
相似文献
5.
6.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
7.
L Zelek R Bugat D Cherqui G Ganem P Valleur R Guimbaud O Dupuis T Aziza P L Fagniez J Auroux H Kobeiter C Tayar A C Braud E Haddad A Piolot M Buyse P Piedbois 《Annals of oncology》2003,14(10):1537-1542
BACKGROUND: The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter. RESULTS: The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months. CONCLUSION: The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation. 相似文献
8.
9.
JM Langley JC LeBlanc EE Wang BJ Law NE MacDonald I Mitchell D Stephens J McDonald FD Boucher S Dobson 《Pediatrics》1997,100(6):943-946
OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality. 相似文献
10.
FJ Cowan JT Warner FD Dunstan WD Evans JW Gregory HR Jenkins 《Archives of disease in childhood》1997,76(4):325-329
The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids. 相似文献