To investigate the effects of human anti-BAFF scFv-Fc against the hsBAFF, ICR mice were randomly divided into six groups: control, hsBAFF (1 mg x kg(-1)), hsBAFF (1 mg x kg(-1)) + Ab (1 mg x kg(-1)), hsBAFF (1 mg x kg(-1)) + Ab (2 mg x kg(-1)), hsBAFF (1 mg x kg(-1)) + human IgG (1 mg x kg(-1)) and hsBAFF (1 mg x kg(-1)) + human IgG (2 mg x kg(-1)) groups. The effects of scFv-Fc administration on the proliferation of B lymphocytes were evaluated using an MTT assay. The titres of antibody in the serum and B lymphocytes differentiation were assessed by ELISA and flow cytometry, respectively. The results showed that administration of scFv-Fc to mice injected with hsBAFF significantly prevented human BAFF-induced increases in splenic B cell numbers and serum immunoglobulin levels. Furthermore, this fully human antibody would avoid inducing the human anti-mouse antibody (HAMA) response when used in humans. These findings suggest that the compact antibody may be useful in therapeutic or diagnostic application of the BAFF-associated autoimmune diseases in human.
Animals ; B-Cell Activating Factor ; immunology ; metabolism ; B-Lymphocytes ; cytology ; Body Weight ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Female ; Humans ; Immunoglobulin Fc Fragments ; immunology ; metabolism ; Immunoglobulin G ; blood ; immunology ; Immunoglobulin M ; blood ; Mice ; Mice, Inbred ICR ; Random Allocation ; Recombinant Fusion Proteins ; immunology ; metabolism ; Single-Chain Antibodies ; immunology ; metabolism ; Spleen ; cytology

OBJECTIVETo investigate the mutation of SOX4 gene in the different tumor tissues with pathological stages and types of non-small cell lung cancer (NSCLC), and to explore its roles in the progression of lung carcinoma.

METHODSThe SOX4 gene HMG-box of lung cancer tissues and paracancerous tissues were amplified by PCR, 20 cases shown difference by single strand conformation polymorphyism analysis were sequenced. The DNA sequences were compared with normal sequences by software Clustal and DNAStar.

RESULTSIn the 90 NSCLCs, 18 cases were found with mutations of SOX4 gene and were sequenced, and there were 2 mutational points. Seven were detected from squamous cell carcinoma, five from adenocarcinoma and six from adeno-squamous. Three were obtained from tissues in stage I, five in stage II, six in stage III, and four in stage IV. The mutation rate in stage II, III and IV was significantly higher than that in stage I.

CONCLUSIONSOX4 gene mutation is not associated with pathology histological types of tumor, but it is significantly associated with pathological stages and the mutation rate increases gradually, which has relation with advanced pathological stages in NSCLC. The results indicate that the SOX4 gene mutations might be related in the lung carcinogenesis and tumor metastasis. The study also provides molecular data for study the links between the mutation of SOX gene and human oncogenesis.

Adult ; Aged ; Aged, 80 and over ; Amino Acid Sequence ; Base Sequence ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Female ; Humans ; Lung Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; SOXC Transcription Factors ; chemistry ; genetics ; Sequence Analysis, DNA

In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5α-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene (SRD5A2). The 5α-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay. Most patients presented with a microphallus, variable degrees of hypospadias, and cryptorchidism. Eight of 14 patients (57.1%) were initially reared as females and changed their social gender from female to male after puberty. Nine mutations were identified in the 14 patients. p.G203S, p.Q6X, and p.R227Q were the most prevalent mutations. Three mutations (p.K35N, p.H162P, and p.Y136X) have not been reported previously. The nonsense mutation p.Y136X abolished enzymatic activity, whereas p.K35N and p.H162P retained partial enzymatic activity. Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results. In conclusion, we expand the mutation profile of SRD5A2 in the Chinese population. A rational clinical approach to this disorder requires early and accurate diagnosis, especially genetic diagnosis.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Adolescent ; Adult ; Asian People/genetics* ; Child ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY/genetics* ; Follicle Stimulating Hormone/blood* ; Genitalia, Male/abnormalities* ; Humans ; Hypospadias/genetics* ; Luteinizing Hormone/blood* ; Male ; Membrane Proteins/genetics* ; Mutation/genetics* ; Sequence Alignment ; Steroid Metabolism, Inborn Errors/genetics* ; Testosterone/blood* ; Young Adult