ABSTRACT
The mechanisms for dominant T15 idiotype selection are not well understood, yet the significance of idiotypic regulation has been suggested. We proposed that to become dominant V regions of a given subset of B-1a cell must establish a functional idiotypic network with complementary T cells. Features required for the cells involved in immune network and steps preceding the establishment of clonal dominance are suggested.
Subject(s)
B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/metabolism , Clonal Selection, Antigen-Mediated , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Thymus Gland/immunology , Thymus Gland/metabolism , Animals , Immunoglobulin Idiotypes/immunology , Mice , Models, Immunological , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolismABSTRACT
The study included 48 untreated patients with monoclonal gammopathies (MG). Paraprotein was isolated from the serum of 10 patients with decreased platelet aggregation. Platelet aggregation was measured before and after the addition of the isolated paraprotein to platelet-rich plasma (PRP) from 10 healthy donors, in vitro. Expression of platelet von Willebrand factor (vWF) receptor glycoprotein (GP)Ib and platelet collagen receptor GPVI was determined by flow cytometry in the PRP of healthy donors before and after the addition of isolated paraprotein using the monoclonal antibodies, CD42b (for GPIb) and CD36 (for GPVI). Flowcytometry showed that expression of CD42b and CD36 positive cells was reduced after the addition of isolated paraprotein to PRP from healthy donors (p < 0.001). These investigations demonstrated that paraprotein causes platelet dysfunction in patients with MG due to specific binding to the platelet vWF receptor GPIb and platelet collagen receptor GPVI.
Subject(s)
Blood Platelets/metabolism , CD36 Antigens/metabolism , Paraproteinemias/diagnosis , Paraproteins/metabolism , Platelet Glycoprotein GPIb-IX Complex/metabolism , Adult , Aged , Aged, 80 and over , Female , Flow Cytometry , Humans , Male , Middle Aged , Paraproteinemias/metabolism , Platelet Aggregation , Platelet-Rich Plasma/metabolism , Protein BindingABSTRACT
PURPOSE: The purpose of this study was to investigate whether the expression of excision repair cross complementing 1 (ERCC1) protein I in tumor tissue was associated with resistance to standard carboplatin and paclitaxel (PC) combination chemotherapy in patients newly diagnosed with advanced epithelial ovarian carcinoma (EOC). METHODS: Fresh frozen tumor tissue was obtained from EOC patients. The protein expression levels of ERCC1 in tumor tissue were determined by Western blot analysis in 55 samples with advanced and metastatic EOC with different histologic subtypes; then these patients were treated with PC. RESULTS: The results showed that the clinical objective responses were significantly different in different categories of ERCC1 protein expression levels in patients with EOC. Time to progression (TTP) and overall survival (OS) in EOC patients previously treated with platinum-based chemotherapy were significantly longer in those with low expression compared with patients showing high expression of ERCC1 protein. CONCLUSION: Our results revealed that ERCC1 protein expression could potentially be used to customize chemotherapy by defining subsets of patients who would benefit the least from platinum-based chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , DNA-Binding Proteins/biosynthesis , Endonucleases/biosynthesis , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Adolescent , Adult , Carboplatin/administration & dosage , Child , Child, Preschool , Female , Humans , Infant , Middle Aged , Paclitaxel/administration & dosage , Prognosis , Prospective Studies , Survival Rate , Treatment Outcome , Young AdultABSTRACT
SOX genes comprise a family of genes that are related to the mammalian sex determining gene SRY in the region that encodes the HMG-box domain responsible for the sequence-specific DNA-binding activity. SOX genes encode putative transcriptional regulators implicated in the decision of cell fates during development and the control of diverse developmental processes. We have cloned and characterised SOX14, a novel member of the human SOX gene family. Based on the HMG-box sequence, human SOX14 is a member of the B subfamily. SOX14 is expressed in human foetal brain, spinal cord and thymus, and like other members of the B subfamily, it might have a role in regulation of nervous system development. While other members of the B subfamily show similarity outside the HMG-box, the regions flanking the HMG box of the human SOX14 gene are unique. SOX14 has been mapped to human chromosome 3q22--> q23, close to the marker D3S1549. This location places SOX14 within a chromosome interval associated with two distinct syndromes that affect craniofacial development: Blepharophimosis-ptosis-epicantus inversus syndrome and Möbius syndrome.
