ABSTRACT
Two new HLA-C alleles have been identified by reverse line blot assay and direct sequencing of polymerase chain reaction (PCR) products. The first polymorphism encodes an amino acid change from lysine in Cw*12022 to asparagine in Cw*1208 at residue 66. The second polymorphism encodes two amino acid changes from isoleucine in Cw*03031 to threonine in Cw*0313 at residue 93 and isoleucine to leucine at residue 94. The functional significance of these polymorphisms on peptide-binding and/or T-cell recognition is unknown.
Subject(s)
Alleles , HLA-C Antigens/genetics , Genes, MHC Class I , Histocompatibility Testing , Humans , Models, Genetic , Molecular Sequence Data , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/pathology , Sequence Analysis, DNA , Sequence Analysis, ProteinABSTRACT
A novel polymorphism was identified in a B*07 allele. B*0722 possesses a unique nucleotide substitution at nucleotide 481. This polymorphism encodes an amino acid difference from aspartic acid in B*07021 to asparagine in B*0722. The functional significance of this polymorphism on peptide binding and/or T-cell recognition is unknown.
Subject(s)
HLA-B Antigens/genetics , Polymorphism, Single Nucleotide , HLA-B7 Antigen , Humans , Multiple Myeloma/genetics , Multiple Myeloma/immunologyABSTRACT
Controlled delivery of chemotherapeutic agents by biodegradable polymers is a new strategy that has been added to the arsenal available for the treatment of malignant neoplasms. This approach is particularly suitable for the management of brain tumours because of the constraints imposed by the blood brain barrier (BBB). The use of polymers for local drug delivery minimises systemic toxicity, while achieving prolonged elevation of intratumoural drug concentrations that results in improved efficacy. In addition, this strategy broadens the spectrum of drugs available for the treatment of neoplasms in the central nervous system to include agents whose efficacy is significantly limited by systemic toxicity or inability to penetrate the BBB. In this review, we discuss the rationale and background for the use of this novel approach. We also summarise the clinical trials and laboratory investigations leading to the development of local delivery of anti-neoplastic agents from biodegradable polymers for the treatment of malignant gliomas.
Subject(s)
Antineoplastic Agents/administration & dosage , Brain Neoplasms/drug therapy , Drug Delivery Systems , Glioma/drug therapy , Animals , Biodegradation, Environmental , Delayed-Action Preparations , Drug Evaluation , Humans , Microspheres , PolymersABSTRACT
HLA matching in bone marrow transplantation has an important role in determining successful outcome. However HLA typing of both potential related and unrelated donors can be both time-consuming and laborious, and does not always resolve accurately the true level of histocompatibility. We have utilised a method, reference strand mediated conformation analysis (RSCA), which is technically simple and allows high resolution matching for all HLA loci, for the typing of 48 patients and their potential 120 donors. The results indicate that RSCA can detect many mismatches that are not routinely identified by conventional HLA typing methods. In addition, RSCA can be applied for the simultaneous analysis of multiple potential BM donor samples in order to quickly identify the best match for each patient.
Subject(s)
Bone Marrow Transplantation/immunology , Histocompatibility Antigens Class II , Histocompatibility Antigens Class I , Histocompatibility Testing/methods , Tissue Donors , Alleles , DNA/blood , DNA/chemistry , DNA/genetics , Evaluation Studies as Topic , Genes, MHC Class I , Genes, MHC Class II , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class II/genetics , Humans , Nucleic Acid Conformation , Polymerase Chain ReactionABSTRACT
We describe the application of RSCA for the high resolution typing of alleles encoded within the highly polymorphic HLA class I system. RSCA differs from other sequence based typing methodologies in that the HLA type is assigned on the basis of differences in DNA conformation between different HLA alleles. HLA class I locus specific PCR was performed on the sample to be HLA typed and the PCR product mixed with a fluorescent labelled locus specific reference strand. DNA molecules were allowed to reanneal and the duplexes formed were separated by non-denaturing PAGE. Only duplexes which possess the fluorescent labelled reference strand were detected using an automated DNA sequencer. The mobilities of duplexes formed for 131 HLA class I alleles have been calculated and HLA type assigned. The use of a laser scanning system for accurate detection of migrating DNA, in combination with specific software for data analysis and correction of gel variablility, make RSCA sufficiently robust to detect alleles differing by as little as one nucleotide, resulting in a simple and automated technique for high resolution HLA typing.
Subject(s)
Alleles , Histocompatibility Antigens Class I/immunology , Histocompatibility Testing/methods , Polymorphism, Genetic , Histocompatibility Antigens Class I/genetics , Humans , Polymerase Chain Reaction/methodsABSTRACT
OBJECTIVES: To provide an introduction to and description of the neurosurgical technologies used for the diagnosis and treatment of central nervous system (CNS) malignancies. DATA SOURCES: Published articles, books, and other reference materials. CONCLUSIONS: Recent advances in the development of assessment tools and surgical techniques have improved the outcome and quality of life for patients with brain and spinal cord tumors. Further improvements in intraoperative instrumentation and postoperative adjuvant therapy are expected to increase the safety and effectiveness of treatments for CNS malignancies. IMPLICATIONS FOR NURSING PRACTICE: Preoperative education for the patient with a CNS malignancy is a special challenge to nurses. Management of these aggressive tumors requires multiple treatment modalities and continued vigilance to detect and palliate recurrent tumors.
