ABSTRACT
<p><b>OBJECTIVE</b>To investigate the flexibility and mobility of the Bacillus thuringiensis toxin Cry1Aa.</p><p><b>METHODS</b>The graph theory-based program Constraint Network Analysis and normal mode-based program NMsim were used to analyze the global and local flexibility indices as well as the fluctuation of individual residues in detail.</p><p><b>RESULTS</b>The decrease in Cry1Aa network rigidity with the increase of temperature was evident. Two phase transition points in which the Cry1Aa structure lost rigidity during the thermal simulation were identified. Two rigid clusters were found in domains I and II. Weak spots were found in C-terminal domain III. Several flexible regions were found in all three domains; the largest residue fluctuation was present in the apical loop2 of domain II.</p><p><b>CONCLUSION</b>Although several flexible regions could be found in all the three domains, the most flexible regions were in the apical loops of domain II.</p>
Subject(s)
Bacillus thuringiensis , Bacterial Proteins , Chemistry , Genetics , Metabolism , Cluster Analysis , Computer Simulation , Endotoxins , Chemistry , Genetics , Metabolism , Entropy , Hemolysin Proteins , Chemistry , Genetics , Metabolism , Models, Structural , Mutation , Protein Conformation , Protein Unfolding , Software , TemperatureABSTRACT
<p><b>OBJECTIVE</b>To investigate the theoretical model of the three-dimensional structure of mosquitocidal Cry30Ca2 and its molecular docking with N-acetylgalactosamine.</p><p><b>METHODS</b>The theoretical model of Cry30Ca2 was predicted by homology modeling on the structure of the Cry4Ba. Docking studies were performed to investigate the interaction of Cry30Ca2 with N-acetylgalactosamine on the putative receptor.</p><p><b>RESULTS</b>Cry30Ca2 toxin is a rather compact molecule composed of three distinct domains and has approximate overall dimensions of 95 by 75 by 60Å. Domain II is a helix bundle, Domain II consists of three antiparallel β-sheets, Domain III is composed of two β-sheets that adopt a β-sandwich fold. Residue 321Ile in loop1, residues 342Gln 343Thr and 345Gln in loop2, residue 393Tyr in loop3 of Cry30Ca2 are responsible for the interactions with GalNAc via 7 hydrogen bonds, 6 of them were related to the oxygen atoms of hydroxyls of the ligand, and one to the nitrogen of the ligand.</p><p><b>CONCLUSION</b>The 3D structure of Cry30Ca2 resembles the previously reported Cry toxin structures but shows still some distinctions. Several residues in the loops of the apex of domain II are responsible for the interactions with N-acetylgalactosamine.</p>
Subject(s)
Animals , Acetylgalactosamine , Chemistry , Amino Acid Sequence , Bacterial Proteins , Chemistry , Pharmacology , Catalytic Domain , Culicidae , Endotoxins , Chemistry , Pharmacology , Hemolysin Proteins , Chemistry , Pharmacology , Insecticides , Chemistry , Pharmacology , Models, Molecular , Molecular Sequence Data , Protein ConformationABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical characteristics and prognosis of primary non-Hodgkin's lymphoma of the breast (PNHLB).</p><p><b>METHODS</b>The characteristics, treatment methods and outcomes of 45 patients with PNHLB were retrospectively analyzed. Chemotherapy including CHOP and CHOP-like regimens was administered in 43 patients, and monoclonal antibody therapy in 6 patients. Furthermore, 19 patients underwent radiotherapy after chemotherapy.</p><p><b>RESULTS</b>Of these 45 patients, 37 patients had diffuse large B cell lymphoma (DLBCL), patients with T cell or mucosa-associated lymphoid tissue (MALT) lymphoma were 4, respectively. Overall response rate of first-line chemotherapy was 90.7%. Median overall survival (OS) and progression-free survival (PFS) of all patients was 6.82 and 4.25 years, respectively. The results of Cox regression model analysis showed that international prognostic index score (IPI) (RR = 5.682, P = 0.002) and Ann Arbor stage (RR = 1.836, P = 0.040) were negative independent prognostic factors for OS. Central nervous system involvement (RR = 1.107, P = 0.005) was a negative independent prognostic factor for PFS.</p><p><b>CONCLUSION</b>The patients with PNHLB have early occurrence in lifespan. Most pathologic type was DLBCL. IPI and Ann Arbor stage are two independent prognostic factors for survival.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antibodies, Monoclonal , Therapeutic Uses , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Breast Neoplasms , Drug Therapy , Pathology , Radiotherapy , Breast Neoplasms, Male , Drug Therapy , Pathology , Radiotherapy , Combined Modality Therapy , Cyclophosphamide , Therapeutic Uses , Disease-Free Survival , Doxorubicin , Therapeutic Uses , Follow-Up Studies , Lymphoma, B-Cell, Marginal Zone , Drug Therapy , Pathology , Radiotherapy , Lymphoma, Large B-Cell, Diffuse , Drug Therapy , Pathology , Radiotherapy , Lymphoma, Non-Hodgkin , Drug Therapy , Pathology , Radiotherapy , Lymphoma, T-Cell , Drug Therapy , Pathology , Radiotherapy , Neoplasm Staging , Prednisone , Therapeutic Uses , Prognosis , Proportional Hazards Models , Radiotherapy, Adjuvant , Remission Induction , Retrospective Studies , Survival Rate , Vincristine , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To evaluate the role of cytogenetic study and interphase FISH analysis in differential diagnosis of patients with clinical and/or cytological diagnosis as lymphoma or "suspicious for lymphoma".</p><p><b>METHODS</b>Routine histology, immunohistochemistry, cytogenetics and interphase FISH studies were used to assess 223 cases with superficial lymph nodes of not less than 1. 5 cm in diameter. The probe used in the interphase FISH assays is the Vysis' LSI IGH Dual Color, Break Apart Rearrangement Probe.</p><p><b>RESULTS</b>Based on these studies, forty-four patients were diagnosed as Hodgkin's lymphomas ( HL) , 162 as Non-Hodgkin's lymphomas ( NHL) , 11 with benign diseases and 4 as other malignancies, while the remaining 2 cases were discarded due to tissue necrosis. Using interphase FISH, abnormalities of immunoglobulin heavy chain gene (IGH) were detected in 6/44 (13.6%) and 83/162 (51.2%) in the HIL and NHL cases, respectively, while none was observed in 11 cases with a benign disease (P <0. 001). Combining cytogenetics and FISH studies, the detection rates for HL and NHL cases then increased to 15.9% and 77. 8%, respectively, otherwise, 3 of whom could not have made definite diagnosis.</p><p><b>CONCLUSION</b>Interphase FISH assay is a rapid and sensitive tool for detecting IGH abnormalities. Both cytogenetics and interphase FISH analyses may play a significant role in diagnosis of lymphomas.</p>