ABSTRACT
Due to the extensive pharmacological effects, pyrazolo[3, 4-d] pyrimidine derivatives have aroused great attention. There are a variety of ways in their synthesis, including using pyrazole ring, pyrimidine ring and other materials as parent ring. The compounds have strong bactericidal, anti-inflammatory, anti-cancer and anti-virus activities, etc. In this paper, the synthesis and pharmacological activities of pyrazolo[3, 4-d] pyrimidine derivatives taking the synthesis as the main line are summarized.
ABSTRACT
In this study, we sought to determine the association between environmental factors and nonsyndromic cleft of the lip and/or palate (NSCLP) to understand the etiology of the disease. A total of 200 NSCLP cases and 327 controls were recruited at the Maternal and Child Health Hospital of Xuzhou City. We conducted face-to-face interviews with the mothers of both cases and controls. The factors increasing the risk of NSCLP were a positive family history [odds ratio (OR)=56.74], pesticide exposure (OR=8.90), and indoor decoration pollution (OR=4.32). On the other hand, the factors decreasing the risk of NSCLP were a high education level (OR=0.22) and supplementation of folic acid (OR=0.23) and multivitamins (OR=0.16). Positive family history, pesticide exposure, and indoor decoration pollution are associated with the risk of NSCLP. In contrast, high education level and folic acid and multivitamin supplementation are protective factors against NSCLP.
Subject(s)
Female , Humans , Infant, Newborn , Pregnancy , Case-Control Studies , China , Epidemiology , Cleft Lip , Epidemiology , Cleft Palate , Epidemiology , Environmental Pollutants , Toxicity , Folic Acid , Therapeutic Uses , Logistic Models , Maternal Exposure , Risk Factors , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
<p><b>OBJECTIVE</b>To study the clinical features of myelodysplastic syndromes (MDS) patients with t (1; 3) (p36; q21) and the expression of the involved genes.</p><p><b>METHODS</b>4 cases of MDS with t (1; 3) (p36; q21) were reported. The expression level of two transcription forms (PR-containing form MEL1 and PR-lacking form MEL1s) of MEL1 gene in normal fetus tissues, 2 healthy donor bone marrows and bone marrows from 3 MDS patients with t (1; 3) (p36; q21) were detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>MDS patients with t (1; 3) (p36; q21) mainly presented with debility. Hemogram was macrocytic anemia, normal or elevated white blood cell and platelet counts. The bone marrow showed tri-lineage dysplasia especially dysmegakaryocytopoiesis. The patients had poor prognosis. MEL1 form was mainly expressed in the normal fetus tissues and healthy bone marrows, while the bone marrow cells from MDS patients with t (1; 3) (p36; q21) mainly or only expressed MEL1s.</p><p><b>CONCLUSIONS</b>MDS patients with t (1; 3) (p36; q21) may be a new unique entity. Overexpression of MEL1s induced by t (1; 3) (p36; q21) might play an important role in the pathogenesis of this entity.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Chromosomes, Human, Pair 1 , Genetics , Chromosomes, Human, Pair 3 , Genetics , DNA-Binding Proteins , Genetics , Myelodysplastic Syndromes , Genetics , Transcription Factors , Genetics , Translocation, Genetic , Zinc Fingers , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To explore genes involved in chronic myeloid leukemia (CML) with t (3; 21) (q26; q22) chromosome translocation in blastic crisis.</p><p><b>METHODS</b>A case of CML patient with t (3; 21) (q26; q22) in blastic crisis was reported. AML1 and bcr/abl genes were detected by FISH in interphase and metaphase cells. Genes involved in t (3; 21) (q26; q22) were analysed by RT-PCR and sequencing.</p><p><b>RESULTS</b>AML1 gene hybridization signal was detected in der (3) and der (21) chromosomes. AML1-Evi1, AML1-MDS1-Evi1, AML1-EAP fusion transcripts and Evi1 gene were detected in mRNA level, but no AML1-Evi1 fusion transcript. The mRNA expression level of AML1-MDS1-Evi1 fusion gene was 1.58 and 1.54 times higher than that of AML1-MDS1 and AML1-EAP, respectively. The mRNA expression level of Evi1 gene of the patient was 2.71 times higher than that of HEL cell line.</p><p><b>CONCLUSION</b>t (3; 21) (q26; q22) resulted in the AML1-MDS1-Evi1, AML1-MDS1, AML1-EAP fusion transcripts, and Evi1 gene was also activated by the translocation. These secondary aberrations should be the molecular basis of CML patient with t (3; 21) (q26; q22) in blastic crisis.</p>
Subject(s)
Adult , Humans , Male , Blast Crisis , Genetics , Pathology , Chromosomes, Human, Pair 21 , Genetics , Chromosomes, Human, Pair 3 , Genetics , Core Binding Factor Alpha 2 Subunit , Genetics , DNA-Binding Proteins , Genetics , Fusion Proteins, bcr-abl , Genetics , Genetic Predisposition to Disease , In Situ Hybridization, Fluorescence , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Genetics , Pathology , MDS1 and EVI1 Complex Locus Protein , Neoplasm Proteins , Genetics , Oncogene Proteins, Fusion , Genetics , Proto-Oncogenes , Genetics , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factors , Genetics , Translocation, GeneticABSTRACT
<p><b>OBJECTIVE</b>To investigate nucleophosmin (NPM) gene mutations in patients with de novo acute myeloid leukemia (AML) with normal cytogenetics and primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Genomic DNA corresponding to exon 12 of NPM gene was amplified by polymerase chain reaction (PCR) in 40 AML patients (28 case untreated and 12 in first remission) and 33 MDS patients. The PCR products were purified and screened by direct sequencing, the mutation PCR products were cloned into pUCm-T vector and then transfected into E. coil DH5alpha. At least 5 recombinant colonies were selected, and plasmid DNA were prepared and sequenced.</p><p><b>RESULTS</b>NPM mutations were found in 6 patients (4 newly diagnosed AML and 2 MDS): 4 were type A,1 type B, and 1 novel sequence variant ( named as type R).</p><p><b>CONCLUSION</b>A new type of NPM mutation was found, and NPM mutations in MDS patients were demonstrated for the first time. The results provides new hints for NPM gene mutations in the pathogenesis of AML and MDS.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Karyotyping , Leukemia, Myeloid, Acute , Genetics , Mutation , Myelodysplastic Syndromes , Genetics , Nuclear Proteins , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between GSTM1, GSTT1 and NQO1(C609T) genotypes and myelodysplastic syndromes (MDS) susceptibility and chromosome abnormalities.</p><p><b>METHODS</b>GSTT1, GSTM1 and NQO1(C609T) genotypes were detected in 52 MDS patients and 241 unrelated controls by PCR or PCR-RFLP.</p><p><b>RESULTS</b>The incidence of GSTT1 and GSTM1 null genotype was significantly increased in MDS patients as compared with controls (P = 0.001 and P < 0.001, respectively). In individuals with GSTT1 and GSTM1 null genotype, the odds ratios for MDS risk were elevated to 2.873 (95% CI: 1.491-5.537) and 3.591 (95% CI: 1.717-7.508), respectively. A significantly increased frequency of GSTT(1) null genotype among MDS patients with normal karyotype and increased frequency of GSTM1 null genotype among MDS patients with chromosome abnormalities were found as compared to controls (OR = 5.336, P = 0.005 and P = 0.003, OR = 3.740, respectively). There was no difference in the incidence of NQO1(C609T) genotypes between MDS patients and controls.</p><p><b>CONCLUSION</b>Determination of the GSTM1 and GSTT1 genotypes may be used as a stratification marker to predicate high-risk individuals for MDS.</p>