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Biomedical subjects

L S Wood

Publications and source records attributed to L S Wood.

7 recordsLinked to original sources
PubMed2005

An association study of 43 SNPs in 16 candidate genes with atorvastatin response.

Variation in individual response to statin therapy has been widely studied for a potential genetic component. Multiple genes have been identified as potential modulators of statin response, but few study findings have replicated. To further examine these associations, 2735 individuals on statin therapy, half on atorvastatin and the other half divided among fluvastatin, lovastatin, pravastatin and simvastatin were genotyped for 43 SNPs in 16 genes that have been implicated in statin response. Associations with low-density lipoprotein cholesterol (LDL-C) lowering, total cholesterol lowering, HDL-C elevation and triglyceride lowering were examined. The only significant associations with LDL-C lowering were found with apoE2 in which carriers of the rare allele who took atorvastatin lowered their LDL-C by 3.5% more than those homozygous for the common allele and with rs2032582 (S893A in ABCB1) in which the two groups of homozygotes differed by 3% in LDL-C lowering. These genetic effects were smaller than those observed with the demographic variables of age and gender. The magnitude of all the differences found is sufficiently small that genetic data from these genes should not influence clinical decisions on statin administration.

Aged↗
PubMed1999

Oprelvekin: an alternative treatment for thrombocytopenia.

Oprelvekin (Neumega, Genetic Institute Co., Cambridge, MA) is a thrombopoietic growth factor approved by the U.S. Food and Drug Administration for the prevention of severe thrombocytopenia following myelosuppressive chemotherapy in patients with nonmyeloid malignancies. The most common side effects are edema, dyspnea, tachycardia, and conjunctival redness. Patient-care concerns include appropriate timing of administration, patient selection, dosing and administration issues, and the early identification and management of side effects.

Antineoplastic Agents↗
PubMed1997

Mutations and deletions within the S8-S9 interdomain region abolish complementation of N- and C-terminal domains of Ca(2+)-activated K+ (BK) channels.

A full length alpha-subunit of the Ca(2+)-activated K+ (BK) channel with an inactivating mutation in the C-terminus can complement a functional C-terminal fragment. We analyzed deletions and amino acid changes within the S8-S9 interdomain region for their ability to allow complementation. Cys612 and His616 that are located in a region that contains two overlapping signature sequences, a immunoglobulin signature sequence and a heme binding domain, are essential for a functional channel. These two amino acid residues are also essential for complementation. The deletion of the PEST sequence does not affect the function of the BK channel; however, without the PEST sequence, complementation by a functional C-terminal fragments is no longer possible. The ability to complement a functional channel is restricted to the C-terminal fragment and requires that the complete alpha-subunit or the larger N-terminal fragment contains both, the immunoglobulin signature sequence the PEST sequence.

Amino Acid Sequence↗
PubMed1997

Molecular cloning of the bovine alpha 1(IV) procollagen gene (COL4A1) and its use in investigating the regulation of expression of type IV procollagen by retinoic acid in bovine lens epithelial cells.

This report is the first to describe the isolation of a 400 base pair cDNA clone encoding part of the bovine alpha 1(IV) procollagen. Using the polymerase chain reaction (PCR), we have amplified a sequence of approximately 400 bp from this gene within the recombinant phage DNA. The cloned sequence encodes 94 amino acids that form part of the protein's helical region. The sequence contains one interruption in the Gly-Xaa-Yaa repeat unit. The third base of the codon for glycine at several sites differs from those seen in murine and human genes, as does the third base of proline codons. The bovine cDNA also contains fewer thymine residues. Northern blot hybridization has shown that the mRNA for bovine procollagen to be 6.2 kb in size. We have used the cDNA clone to investigate the effect of all-trans retinoic acid (RA) on the gene expression of alpha 1(IV) procollagen in cultured bovine lens epithelial (LE) cells. We have also observed that RA decreases total protein production and concomitantly increases type IV procollagen in a concentration dependent manner. An increase in alpha 1(IV)mRNA as well as increase in type IV procollagen suggest that the regulation of alpha 1(IV) gene by RA in the LE cells is at the transcriptional level. Further, our results support the hypothesis that RA inhibition of lens epithelium transformation to fibroblast-like cells may be due to the ability of RA to stimulate the production of basement membrane components by epithelia.

Amino Acid Sequence↗
PubMed1995

Cloning and functional expression of a human gene, hIRK1, encoding the heart inward rectifier K+-channel.

We have isolated a cDNA clone encoding a human inward rectifier potassium channel (hIRK1). The nucleotide (nt) sequence of the coding region is 88% similar to the mouse clone with only seven amino-acid (aa) differences. The hIRK1 cRNA initially expressed low levels of protein in a wheat germ system and in Xenopus oocytes. The addition of a SmaI site 3' to the poly(A) tail increased the expression at least tenfold. Xenopus oocytes injected with the hIRK1 cRNA developed resting potentials that averaged -96 mV and a large inward current that was blocked by Ba2+ or Cs+. The hIRK1 EK shifted 54.6 mV per decade change in [K]o, and its channel conductance increased with [K]o by a 0.3 exponent factor. Above EK, the hIRK1 I-V relation has a distinct 'N'-shape. Cell-attached single-channel conductance in 140 mM K+ pipette solution averaged 29 pS. The negative resting potential and the 'N'-shape I-V relation of hIRK1 closely resemble that of the native cardiac inward rectifier IK1.

Amino Acid Sequence↗