Biomedical subjects

C I E Smith

Publications and source records attributed to C I E Smith.

4 recordsLinked to original sources

PubMed2004

Adding functional entities to plasmids.

Non-viral gene therapy constitutes an alternative to the more common use of viral-mediated gene transfer. Most gene transfer methods using naked DNA are based upon non-sequence-specific interactions between the nucleic acid and cationic lipids (lipoplex) or polymers (polyplex). We have developed a technology in which functional entities hybridize in a sequence-specific manner to the nucleic acid (bioplex). This technology is still in its infancy, but has the potential to become a useful tool, since it allows the construction of highly defined complexes containing a variety of functional entities. In its present form the bioplex technology is based upon the use of peptide/nucleic acids (PNA) as anchors. Single, or multiple, functional entities are directly coupled to the anchors. By designing plasmids, or oligonucleotides, with the corresponding anchor target sequence, complexes with desired composition can easily be generated. The long-term aim is to combine functional entities in order to achieve optimal, synergistic interactions allowing enhanced gene transfer in vivo.

Cell Nucleus↗

PubMed2003

High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a moderately aggressive B-cell lymphoma that responds poorly to currently used therapeutic protocols. In order to identify tumour characteristics that improve the understanding of biology of MCL, analysis of oligonucleotide microarrays were used to define specific gene expression profiles. Biopsy samples of MCL cases were compared to reactive lymphoid tissue. Among genes differentially expressed in MCL were genes that are involved in the regulation of proliferation, cell signalling, adhesion and homing. Furthermore, some genes with previously unknown function, such as C11orf32, C2orf10, TBC1D9 and ABCA6 were found to be differentially expressed in MCL compared to reactive lymphoid tissue. Of special interest was the high expression of the cannabinoid receptor 1 (CB1) gene in all MCL cases analysed. These results were further confirmed at the cellular and protein level by immunocytochemical staining and immunoblotting of MCL cells. Furthermore, there was a reduced expression of a regulator of G protein signalling, RGS13 in all MCLs, with a complete absence in the majority of cases while present in control lymphoid tissue. These results were further confirmed by PCR. Sequencing of the RGS13 gene revealed changes suggesting polymorphisms, indicating that downregulation of the expression of RGS13 is not related to mutations, but may serve as a new specific marker for MCL. Moreover, comparison between individual cases of MCL, revealed that the CCND1 gene appears to be differently expressed in MCL cases with high vs low proliferative activity.

Adolescent↗

PubMed2002

Express subcutaneous IgG infusions: decreased time of delivery with maintained safety.

The aims of the study were to evaluate the safety and feasibility of weekly express subcutaneous replacement IgG self-infusions (E-SCIG, 35 mL/h/syringe driver) in 50 patients and to evaluate their perceptions of the therapy. A total of 4900 E-SCIG infusions at separate infusion sites were given on 1228 treatment occasions. The most commonly reported local tissue reactions were swelling (n = 37), redness (n = 25), and soreness (n = 24). A majority of these patients reported the local reactions as less intense or unchanged compared to those arising from rapid SCIG (20 mL/h) infusions. The patients reported a median score of 16 (visual analogue scale, VAS; 1, not troublesome at all) regarding their overall perceptions of the local reactions. They were positive toward the home therapy regime (median VAS score 96; 100, very positive) and anxious to continue with the E-SCIG infusions (median VAS score 98; 100, very anxious). The E-SCIG method seems to be safe, with few pronounced local reactions, and is appreciated by the patients. Express delivery could also potentially facilitate IgG delivery in a wide variety of diseases, such as autoimmune and autoimmune-like conditions of a neurological or rheumatological character.

Administration, Cutaneous↗

PubMed2002

Clinical and molecular analysis of patients with defects in micro heavy chain gene.

Autosomal recessive disorders of B cell development are rare and heterogeneous. To determine the proportion of affected patients who have defects in the micro heavy chain (IGHM) gene, we used single-stranded conformational polymorphism analysis to screen genomic DNA from 40 unrelated patients with early onset infections, profound hypogammaglobulinemia, and absent B cells. All of the patients were genotypically normal in BTK, the gene that underlies X-linked agammaglobulinemia. Eight different mutations in the micro heavy chain were identified in 19 members of 12 unrelated families. Four of the mutations were large deletions that removed more than 40 kb of DNA in the IGHM locus. In six of the 12 families, the affected patients had an identical single base pair substitution, a G-->A, at the -1 position of the alternative splice site. Immunoglobulin haplotype analysis showed that this mutation occurred on at least three different haplotypes, indicating that this is a hot spot for mutations. Compared with patients with mutations in Btk, patients with defects in the micro heavy chain had an earlier onset of disease and more complications. Our study indicates that at least 20-30% of patients with autosomal recessive defects in B cell development have mutations in the micro heavy chain.

Adolescent↗