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Biomedical subjects

A Mazumder

Publications and source records attributed to A Mazumder.

151 records · Page 9Linked to original sources

A phase 1a clinical trial of LYM-1 monoclonal antibody serotherapy in patients with refractory B cell malignancies.

Ten patients with refractory B cell lymphomas were treated with weekly intravenous infusions of escalating doses of murine monoclonal antibody (MoAb) LYM-1 over four weeks. LYM-1 is a recently developed IgG2a murine MoAb that recognizes a polymorphic HLA-Dr antigen on surfaces of normal and malignant B cells but does not bind to any other normal tissues. MoAb LYM-1 has several advantages for serotherapy, since the antigen it recognizes is not shed from the cell surface and does not modulate in response to MoAb therapy. Furthermore, in vitro studies have indicated significant anti-tumour activity against lymphoma cell lines. In the current trial, dose-dependent levels of free LYM-1 were detected in the serum of all patients, but penetration of extravascular tumour tissues was poor. No significant toxicity or human anti-mouse antibody responses were observed in any patient. Clinical responses were minor and appeared to correlate with the number of infiltrating T cells seen in the initial lymphoma specimens. LYM-1 appears to be well-tolerated and has demonstrated several potential advantages as a therapeutic agent in patients with lymphoma. The mechanism of anti-tumour effect and plans for further clinical studies are discussed.

Adult↗

Nuclease activity of 1,10-phenanthroline-copper. New conjugates with low molecular weight targeting ligands.

The chemical nuclease activity of 1,10-phenanthroline-copper depends on DNA sequence because the coordination complex has affinity for DNA. In order to target this efficient nucleolytic activity, it is essential to override its inherent specificity. The minimal size of ligands capable of redirecting the specificity has been investigated. A conjugate (HOP) prepared by alkylating Hoechst dye 33258 with 5-(iodoacetamido)-1,10-phenanthroline has a greater preference for A-T-rich regions than the unsubstituted 1,10-phenanthroline-copper complex, reflecting the specificity of this A-T-specific minor-groove binder. However, since quaternizing the dye with 5-(iodoacetamido)-1,10-phenanthroline increases its affinity for DNA, the specificity of cleavage by the conjugate is less than the binding selectivity of the dye. Linking 1,10-phenanthroline with the peptide of the helix-turn-helix domain of the Trp repressor specificity results in a conjugate with greater reactivity for the operator sequence than the unsubstituted complex. The intrinsic affinity of the 1,10-phenanthroline-Cu can only be partially overridden by the conformationally unstable peptide. Attachment of 1,10-phenanthroline to a deoxyoligonucleotide complementary to a single-stranded loop of RNA successfully targets the scission of the chemical nuclease. Cleavage sites are observed not only contiguous to the site of hybridization but also at nonadjacent sequence positions. The latter set of sites must be close in space to the 5' end of the hybridized deoxyoligonucleotide.

Alkylation↗

Solid-phase oligonucleotide synthesis and flow cytometric analysis with microspheres encoded with covalently attached fluorophores.

A novel combinatorial approach to synthesize oligonucleotides on fluorescently encoded microspheres based on flow sorting and segmental solid-phase synthesis is described. BODIPY dyes were covalently attached to polystyrene (8.8 microm, 55% DVB) microsphere particles to generate four fluorescently encoded sets. 20-mer oligonucleotide sequences can be synthesized on these microspheres with yields comparable to conventional CPG supports (80% overall yield, average stepwise yield = 99%). The concept of segmental solid-phase synthesis by flow sorting was demonstrated by synthesizing unique 20-mer oligonucleotide sequences on each of four fluorescently encoded microsphere sets by including a flow sorting step (after first eight base additions) and flow cytometric detection of sequences synthesized on each microsphere set by hybridization with fluorescently labeled complementary sequence.

Boron Compounds↗

The use and evaluation of 2 + 2 photoaddition in immobilization of oligonucleotides on a three dimensional hydrogel matrix.

Photochemical attachment of synthetic oligonucleotides on the three dimensional surface of a polyacrylamide based hydrogel was used in the specific detection of target oligonucleotides. Covalent attachment of the oligonucleotide to the hydrogel was mediated by the incorporation of a 2 + 2 photo-attachable functional group in both the hydrogel and the oligonucleotide probe. Expression and SNP assays were used to evaluate this platform.

Acrylic Resins↗

Comparative study of hemopoietic precursors from fetal and adult bone marrow: utilization of stem cells derived from miscarriages.

Hemopoietic and immune capacities of fetal bone marrow (FBM) obtained from 2nd-trimester lost pregnancies and adult bone marrow (ABM) were compared. Progenitor cell assays for both sources were also enumerated. Out data showed ontogeny-related functional differences between hemopoietic cells, particularly in the ability to produce CD34+ cells (24.6% in FBM, 3.1% in ABM). The phenotypic composition of FBM and ABM were quite different. The clonogenic/proliferative potentials, as measured by CFU-C assays, were significantly higher in FBM when compared to ABM (202.5 vs. 73.5/10(5) cells). Moreover, FBM had a lower percentage of CD3+ T lymphocytes as compared to ABM (1.47 vs. 7.58), and there was a significantly decreased proliferative responsiveness in mixed lymphocyte reactions of FBM as compared to ABM. Thus, our data clearly showed distinct advantages of FBM over ABM, which include a higher number of stem cells, lower immunological reactivity, and higher clonogenic/proliferative potential. These characteristics provide optimal conditions for successful engraftment without graft-versus-host disease. These data support the possible advantages of FBM from these sources for hemopoietic stem cell reconstitution and gene therapy.

Abortion, Spontaneous↗