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101.
102.
Cristina Ferr��s Joachim AF Oude Vrielink Johan WA Verspuy Hein te Riele Anastasia Tsaalbi-Shtylik Niels de Wind 《Molecular therapy》2009,17(8):1373-1380
A substantial fraction of sporadic and inherited colorectal and endometrial cancers in humans is deficient in DNA mismatch repair (MMR). These cancers are characterized by length alterations in ubiquitous simple sequence repeats, a phenotype called microsatellite instability. Here we have exploited this phenotype by developing a novel approach for the highly selective gene therapy of MMR-deficient tumors. To achieve this selectivity, we mutated the VP22FCU1 suicide gene by inserting an out-of-frame microsatellite within its coding region. We show that in a significant fraction of microsatellite-instable (MSI) cells carrying the mutated suicide gene, full-length protein becomes expressed within a few cell doublings, presumably resulting from a reverting frameshift within the inserted microsatellite. Treatment of these cells with the innocuous prodrug 5-fluorocytosine (5-FC) induces strong cytotoxicity and we demonstrate that this owes to multiple bystander effects conferred by the suicide gene/prodrug combination. In a mouse model, MMR-deficient tumors that contained the out-of-frame VP22FCU1 gene displayed strong remission after treatment with 5-FC, without any obvious adverse systemic effects to the mouse. By virtue of its high selectivity and potency, this conditional enzyme/prodrug combination may hold promise for the treatment or prevention of MMR-deficient cancer in humans. 相似文献
103.
The purpose of this study was to determine the degree of informant agreement for behavioral ratings of children with epilepsy. Informants completed Achenbach's 1991 scales: parents completed the Child Behavior Checklist (CBCL), teachers completed the Teacher's Report Form (TRF), and youth completed the Youth Self-Report Form of the CBCL (YSR). Analyses included degree of concordance of ratings as a function of informant, child gender, and condition severity (active vs inactive epilepsy). Results indicated that across all four types of raters (mothers, fathers, teachers, and adolescents) there was a similar pattern. Mothers' ratings tended to be the highest and youths' ratings tended to be the lowest across scales. In general, agreement among adult raters was greater than between youth and adults. Mothers and teachers reported more internalizing symptoms than did youth; mother, father, and teacher ratings on externalizing symptoms were not significantly different from each other. There were no significant effects of gender and condition severity on concordance among ratings although there were some interesting trends. 相似文献
104.
High-dose 131I-metaiodobenzylguanidine therapy for 12 patients with malignant pheochromocytoma 总被引:6,自引:0,他引:6
BACKGROUND: 131I-Metaiodobenzylguanidine (131I-MIBG) can be used systemically to treat malignant pheochromocytoma. To improve outcome, the authors used higher levels of activity of 131I-MIBG than previously reported. The authors reported the response rates and toxicity levels in patients with malignant pheochromocytoma or paraganglioma who were treated with high-dose 131I-MIBG. METHODS: Following debulking surgery and stem cell harvest, 12 patients with malignant pheochromocytoma or paraganglioma were treated with 131I-MIBG. Five had received previous external beam radiation and/or chemotherapy. The median single treatment dose was 800 mCi (37 gigabecquerels; range, 386-866 mCi) or 11.5 mCi/kg (range, 5.6-18.3 mCi/kg). The median cumulative dose was 1015 mCi (range, 386-1690 mCi). RESULTS: Three patients had a complete response, two of whom had soft tissue and skeletal metastases. Their median follow-up was 45 months (range, 23-101 months). Seven patients had a partial response (PR), with a median follow-up 43 months (range, 6-47 months). Two patients without a response died with progressive disease (PD) and 2 patients with an initial PR died of PD at 13 and 11 months, respectively. Grade 3 thrombocytopenia occurred after 79% (15 of 19) of treatments had been administered. Grade 3 and 4 neutropenia followed 53% (10 of 19) and 19% (4 of 19) of treatments, respectively. One patient required stem cell infusion, and one developed primary ovarian failure. CONCLUSIONS: The single and cumulative doses of 131I-MIBG were approximately 2-3.5 times higher than those used at other centers. Unlike previous reports, two patients with both skeletal and soft tissue metastases had a complete response. Hematologic toxicity was significant but tolerable. High-dose 131I-MIBG may lead to long-term survival in patients with malignant pheochromocytoma. 相似文献
105.
YF NGEOW AF WEIL NS KHAIRULLAH MY MOHD YUSOF L LUAM C GAYDOS TC QUINN 《Journal of paediatrics and child health》1997,33(5):422-425
Objective: The incidence of Chlamydia pneumoniae and Chlamydia trachomatis infection was studied among infants and young children admitted to hospital for the management of lower respiratory tract infections, over a 12 month period.
Methodology: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods.
Results: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively.
Conclusion: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia. 相似文献
Methodology: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods.
Results: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively.
Conclusion: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia. 相似文献
106.
107.
Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR 总被引:12,自引:2,他引:12
Cremers FP; van de Pol DJ; van Driel M; den Hollander AI; van Haren FJ; Knoers NV; Tijmes N; Bergen AA; Rohrschneider K; Blankenagel A; Pinckers AJ; Deutman AF; Hoyng CB 《Human molecular genetics》1998,7(3):355-362
Ophthalmological and molecular genetic studies were performed in a
consanguineous family with individuals showing either retinitis pigmentosa
(RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive)
inheritance of allelic defects, linkage analysis positioned the causal gene
at 1p21-p13 (lod score 4.22), a genomic segment known to harbor the ABCR
gene involved in Stargardt's disease (STGD) and age- related macular
degeneration (AMD). We completed the exon-intron structure of the ABCR gene
and detected a severe homozygous 5[prime] splice site mutation,
IVS30+1G->T, in the four RP patients. The five CRD patients in this
family are compound heterozygotes for the IVS30+1G- >T mutation and a
5[prime] splice site mutation in intron 40 (IVS40+5G- >A). Both splice
site mutations were found heterozygously in two unrelated STGD patients,
but not in 100 control individuals. In these patients the second mutation
was either a missense mutation or unknown. Since thus far no STGD patients
have been reported to carry two ABCR null alleles and taking into account
that the RP phenotype is more severe than the STGD phenotype, we
hypothesize that the intron 30 splice site mutation represents a true null
allele. Since the intron 30 mutation is found heterozygously in the CRD
patients, the IVS40+5G->A mutation probably renders the exon 40 5[prime]
splice site partially functional. These results show that mutations in the
ABCR gene not only result in STGD and AMD, but can also cause autosomal
recessive RP and CRD. Since the heterozygote frequency for ABCR mutations
is estimated at 0.02, mutations in ABCR might be an important cause of
autosomal recessive and sporadic forms of RP and CRD.
相似文献
108.
We report the case of an 8 week old infant with fulminant autoimmune haemolytic anaemia refractory to conventional immunomodulating treatment. Massive haemolysis resulted in cardiac decompensation and acute renal failure which necessitated mechanical ventilation and peritoneal dialysis. Rituximab, a chimeric anti-CD20 monoclonal antibody, halted progression of the haemolytic process, but the patient died of acute viral pneumonia and disseminated fungal infection. Earlier introduction of rituximab might have prevented the renal complications. Paediatricians should be aware of this useful therapeutic tool for treatment of refractory autoimmune haemolytic anaemia and balance its use against the risk of potential life threatening infection. 相似文献
109.
院内感染严重影响重症监护室(ICU)危重病人的治疗。目前5例院内感染病例中就有1例是发生在ICU病房。院内输血感染(blood stream injections,BSIs)使危重病人的监护面临重大挑战。虽然输血感染的死亡率还存在争议,但大量的报道已经证实ICU内菌血症的增多使病人住院时间及费用均有所上升。如一项研究证实患院内菌血症后患者ICU住院期增加〉7天,住院费用额外增加〉2万美元。耐药菌群的不断出现与ICU病人病情加重进一步增加了BSIs的治疗难度。 相似文献
110.