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Biomedical subjects

G Parkinson

Publications and source records attributed to G Parkinson.

10 recordsLinked to original sources
PubMed2001

A new class of symmetric bisbenzimidazole-based DNA minor groove-binding agents showing antitumor activity.

The synthesis and evaluation of the novel head-to-head bisbenzimidazole compound 2,2-bis[4'-(3' '-dimethylamino-1' '-propyloxy)phenyl]-5,5-bi-1H-benzimidazole is described. An X-ray crystallographic study of a complex with the DNA dodecanucleotide sequence d(CGCGAATTCGCG) shows the compound bound in the A/T minor groove region of a B-DNA duplex and that the head-to-head bisbenzimidazole motif hydrogen-bonds to the edges of all four consecutive A:T base pairs. The compound showed potent growth inhibition with a mean IC(50) across an ovarian carcinoma cell line panel of 0.31 microM, with no significant cross-resistance in two acquired cisplatin-resistant cell lines and a low level of cross-resistance in the P-glycoprotein overexpressing acquired doxorubicin-resistant cell line. Studies with the hollow fiber assay and in vivo tumor xenografts showed some evidence of antitumor activity.

Animals↗
PubMed2000

A new crystal form for the dodecamer C-G-C-G-A-A-T-T-C-G-C-G: symmetry effects on sequence-dependent DNA structure.

The dodecanucleotide d(CGCGAATTCGCG) has been crystallised in the space group P3(2)12, representing a new crystal form for this sequence. The structure has been solved by molecular replacement and refined at 1.8 A resolution. The present structure contrasts with previous ones for this sequence since it is situated on a crystallographic 2-fold axis, and the crystal symmetry reflects the palindromic nature of this sequence. Some features accord with previous observations, notably that the minor groove is hydrated with a continuous spine of solvent. There is no evidence of alkali metal ions within this spine. The minor groove retains its narrow width, although it is now symmetric and extends over the A/T tract. Various base and base-pair morphological parameters have been examined. Their values do not show significant correlations with earlier reports, suggesting that crystal packing effects on them are more dominant than has been hitherto realised.

Base Pairing↗
PubMed1997

Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides.

OBJECTIVE: To investigate potential mechanisms by which CD40L-mediated signals may be involved in the pathogenesis of lupus glomerulonephritis (GN). METHODS: Renal in situ CD40L and CD40 expression was examined in patient biopsy specimens. Immunohistochemical studies were performed on frozen sections utilizing anti-CD40L monoclonal antibody (MAb), anti-CD40 MAb, or control MAb. As controls, we analyzed normal kidney specimens and specimens obtained from patients with IgA nephropathy, focal segmental glomerulosclerosis, minimal change disease, idiopathic membranous GN, and antineutrophil cytoplasmic antibody-positive pauci-immune GN. Staining distribution was noted and staining intensity scored on a semiquantitative scale of 0 (no staining) to 3+ (intense staining). RESULTS: In normal kidney, CD40 was expressed on parietal epithelial cells, mesangial cells, endothelial cells, and distal tubules but not proximal tubules. Glomerular and tubular CD40 expression was markedly up-regulated in class III and class IV lupus GN, where there was intense staining of crescents, proximal and distal tubules, and interstitial mononuclear cells. In contrast, CD40 expression in class V lupus GN was similar to that in normal kidney. Interstitial mononuclear cells expressing CD40L were present in class IV lupus GN. However, these findings were not unique to lupus GN: up-regulation of CD40 and CD40L expression was similarly observed in other inflammatory renal diseases. CONCLUSION: This study shows that CD40 is expressed on a variety of renal parenchymal and non-parenchymal cells in normal kidney. Renal CD40 expression is up-regulated in class III and class IV lupus nephritis, as well as in other inflammatory renal diseases, and is associated with the presence of CD40L+ mononuclear cells.

Adolescent↗
PubMed1996

Structure of the CAP-DNA complex at 2.5 angstroms resolution: a complete picture of the protein-DNA interface.

The crystallographic structure of the CAP-DNA complex at 3.0 A resolution has been reported previously. For technical reasons, the reported structure had been determined using a gapped DNA molecule lacking two phosphates important for CAP-DNA interaction. In this work, we report the crystallographic structure of the CAP-DNA complex at 2.5 A resolution using a DNA molecule having all phosphates important for CAP-DNA interaction. The present resolution permits unambiguous identification of amino acid-base and amino acid-phosphate hydrogen bonded contacts in the CAP-DNA complex. In addition, the present resolution permits accurate definition of the kinked DNA conformation in the CAP-DNA complex.

Base Composition↗
PubMed1996

New parameters for the refinement of nucleic acid-containing structures.

Structures at atomic resolution (up to 1.0 A) which contain bases, sugars or the phosphodiester linkage, were selected from the Nucleic Acid Database or the Cambridge Structural Database to build a nucleic acid dictionary from X-ray refined structures. The dictionary consists of the average values for bond distances, bond angles and dihedral angles. The variance of the sample is used to provide information about the expected r.m.s. deviations of the refined parameters. A dictionary was constructed for refinement trials in X-PLOR. The dictionary includes RNA and DNA in C2'-endo and C3'-endo sugar pucker conformations, as well as values for the backbone dihedrals. Tests were performed on the dictionary using three structures: a B-DNA, a Z-DNA and a protein-DNA complex. During the course of refinement, all three structures showed significant improvements as measured by r.m.s. deviations and R factors when compared to the previous DNA dictionary.

Journal Article↗
PubMed1996

Sequential studies of endochondral ossification and serum 1,25-dihydroxycholecalciferol in broiler chickens between one and 21 days of age.

Two commercial broiler flocks of two distinct strains (A and B) were studied at weekly intervals from day old to 21 days, to assess the progressive endochondral ossification of the proximal tibiotarsus and the serum concentration of 1,25-dihydroxycholecalciferol (1,25(OH)2D3). The incidence of defects of endochondral ossification was different in the two strains, strain B having an incidence of tibial dyschondroplasia (TD) of 10 to 70 per cent and strain A an incidence of 10 to 20 per cent. In strain B, 40 per cent of the bone samples collected at 14 days of age also had lesions of calcium deficiency rickets. The concentration of 1,25(OH)2D3 in the two flocks was similar in the day-old chicks, but was 40 to 50 per cent lower at seven, 14 and 21 days of age in strain B, during the development of the rachitic and dyschondroplastic lesions. These results suggest that TD in some broiler strains is related to an inherent predisposition to rickets and to lower serum concentrations of 1,25(OH)2D3.

Aging↗
PubMed1994

Weight of internal organs and carcase yield of early food restricted broilers broilers.

1. Effects of food restriction on growth rate and relative growth rates of supply organs (liver, heart, lungs and kidneys, digestive tract) and demand organs (breast, back, thighs, abdominal fat) of broiler chickens were studied. 2. Birds were restricted in intake to 50% (group FI 50) or 75% (group FI 75) of ad libitum from 5 to 11 d of age; all birds were fed ad libitum from 12 to 39 d of age. 3. Relative growth rates from 12 to 39 d of age of group FI 50 were higher (P < 0.05) than group FI 75 and control group. 4. No significant differences in food conversion ratio, carcase fat and abdominal fat between groups were observed. 5. At 12 d of age, relative weight of the empty digestive tract of group FI 50 was higher (P < 0.05) than that of the control group and group FI 75. 6. The increased weight of the empty digestive tract may have contributed to the ability of the chickens to achieve compensatory growth after the restriction period.

Adipose Tissue↗