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C Laing

Publications and source records attributed to C Laing.

15 recordsLinked to original sources
PubMed2001

Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a group of inherited defects of dental enamel formation that shows both clinical and genetic heterogeneity. To date, mutations in the gene encoding amelogenin have been shown to underlie a subset of the X-linked recessive forms of AI. Although none of the genes underlying autosomal-dominant or autosomal-recessive AI have been identified, a locus for a local hypoplastic form has been mapped to human chromosome 4q11-q21. In the current investigation, we have analysed a family with an autosomal-dominant, smooth hypoplastic form of AI. Our results have shown that a splicing mutation in the splice donor site of intron 7 of the gene encoding the enamel-specific protein enamelin underlies the phenotype observed in this family. This is the first autosomal-dominant form of AI for which the genetic mutation has been identified. As this type of AI is clinically distinct from that localized previously to chromosome 4q11-q21, these findings highlight the need for a molecular classification of this group of disorders.

Amelogenesis Imperfecta↗
PubMed2000

Are calcium antagonists effective in preventing complications of hypertension and progression of renal disease?

Long-acting calcium antagonists have been shown to be safe and effective in lowering blood pressure, both as first-line agents and in combination with other classes of antihypertensive drug. They have also been shown to reduce the incidence of cerebrovascular and cardiovascular events in elderly patients with predominantly systolic hypertension. It is clear that reduced morbidity and mortality in hypertension is related to the degree to which blood pressure is reduced, regardless of the therapy used. This is the single most important conclusion of all recent trials, especially in the sub-group of hypertensive patients with diabetes. The World Health Organization-International Society of Hypertension guidelines acknowledge this and do not make specific recommendations as to initial therapy in the absence of other medical factors. However the use of thiazide diuretics and beta-blockers has strong support from large placebo-controlled trials in patients with mild-moderate essential hypertension. The British Hypertension Society and JNC VI guidelines restrict their recommendations for the use of calcium antagonists to isolated systolic hypertension and angina, or when other agents have failed, are contraindicated or are not tolerated. However, their efficacy in lowering blood pressure, their tolerability and potentially beneficial secondary effect on proteinuria, especially in combination with an angiotensin-converting enzyme inhibitor, still make them attractive antihypertensive agents. The results of further long-term outcome trials that make direct comparisons between calcium antagonists and other classes of antihypertensive drug are still awaited. Unlike angiotensin-converting enzyme inhibitors, the antiproteinuric effect of calcium antagonists, even that of the non-dihydropyridine type, seems to depend on an adequate and stable reduction in blood pressure.

Calcium Channel Blockers↗
PubMed1997

Rickets in a litter of racing greyhounds.

Rickets was diagnosed in six 14-week-old racing greyhound littermates presented with musculoskeletal disease. Physical findings included listlessness, profound muscle weakness, lameness, lateral bowing of the antebrachii and focal hard swellings proximal to the tarsi and carpi. Radiological findings included generalised osteopenia, axial and radial thickening of growth plates, and "cupping' of the adjacent metaphyses; the distal ulnar growth plates were most severely and consistently affected. The diagnosis was confirmed by demonstrating subnormal concentrations of 25-hydroxycholecalciferol in serum samples collected at admission. The pups' diet consisted of an inexpensive generic kibble formulated for adult dogs, porridge, milk, pasta, minced beef, vegetables and a small quantity of calcium carbonate powder. The pups were successfully treated by feeding a nutritionally complete, vitamin D-containing ration formulated for growing pups. Bilateral growth retardation of distal ulnar physes occurred as a sequel in one pup.

Animals↗
PubMed1995

Jasplakinolide's inhibition of the growth of prostate carcinoma cells in vitro with disruption of the actin cytoskeleton.

BACKGROUND: Jasplakinolide, a cyclodepsipeptide produced by an Indo-Pacific sponge, Jaspis johnstoni, has been reported to inhibit the growth of breast cancer cells. PURPOSE: The effects of jasplakinolide on the proliferation of three human immortalized prostate carcinoma cell lines (PC-3, LNCaP, and TSU-Pr1) were studied. The growth-inhibitory effect of jasplakinolide on the PC-3 cell line was studied in detail to elucidate its mechanism of action. METHODS: Cell counts were used to study growth inhibition. A protein-based microplate assay was used to assess the time of exposure needed to cause persistent growth inhibition and to study the effects of jasplakinolide analogues. Metabolic changes were assessed by following the incorporation of radiolabeled precursors. The effects of jasplakinolide on the cytoskeleton were studied by fluorescent microscopy, using rhodamine phalloidin (RP) and antibodies to cytoskeletal components. Changes in RP binding were quantified by extracting bound fluorescent material from fixed cells and measuring the amount of fluorescence in a spectrofluorometer. RESULTS: The growth of PC-3, LNCaP, and TSU-Pr1 cells was potently inhibited by exposure to jasplakinolide for 48 hours; doses of jasplakinolide that led to 50% growth inhibition were 65 nM for PC-3 cells, 41 nM for LNCaP cells, and 170 nM for TSU-Pr1 cells. In PC-3 cells, exposure to 160 nM for 48 hours led to total growth inhibition, which persisted for several days even after drug removal. Several jasplakinolide analogues also inhibited the growth of PC-3 cells, although analogues in which the rigidity of the macrolide ring was altered were ineffective. No early changes in the synthesis of DNA, RNA, or protein or in intracellular adenosine triphosphate levels were seen in the PC-3 cells after exposure to jasplakinolide. Growth inhibition by jasplakinolide was accompanied by striking morphologic changes. Exposure for several doublings led to multinucleated cells. Further investigation of these changes in the PC-3 cells revealed a dramatic and early disruption of the actin cytoskeleton and a statistically significant decrease in RP binding. The doses of jasplakinolide, the time of exposure, and the pattern of growth inhibition by structural analogues corresponded with the changes seen in actin distribution. CONCLUSIONS: Jasplakinolide represents a novel marine natural product with potent in vitro antiproliferative activity against human prostate carcinoma cell lines, and it appears to target the actin cytoskeleton. IMPLICATIONS: Jasplakinolide is a potential candidate for further preclinical development and a lead structure for a novel class of therapeutic agents that can disrupt the actin cytoskeleton in mammalian cells.

Actins↗
PubMed1992

Optimized determination of malondialdehyde in plasma lipid extracts using 1,3-diethyl-2-thiobarbituric acid: influence of detection method and relations with lipids and fatty acids in plasma from healthy adults.

We investigated the influence of different concentrations of Fe3+, phosphoric acid, butylated hydroxytoluene and glutathione on the production of the malondialdehyde-1,3-diethyl-2-thiobarbituric acid adduct in plasma lipid extracts. Following organic solvent extraction the stable product was analyzed by spectrophotometry (537 nm), fluorometry (547 nm) and high-performance liquid chromatography with fluorometric detection. Using optimized reaction conditions there was good agreement between the three methods, with slightly higher values for the spectrophotometric method. Plasma total lipid malondialdehyde reference values for 24 healthy adults amounted to 1.30 +/- 0.23 mumol/l (spectrophotometric method) and 1.11 +/- 0.31 mumol/l (fluorometric method). Plasma lipid malondialdehyde concentrations correlated significantly with plasma triglycerides (r = 0.527), total cholesterol (r = 0.612) and total fatty acids (r = 0.810) and with the total number of double bonds present in plasma fatty acids with three or more double bonds (r = 0.923).

Adult↗
PubMed1983

Dialysis leucopenia--no correction after prolonged washing of the membrane.

Re-use of hemodialysers diminishes the extent of leucopenia observed during hemodialysis. A possible cause of this change is the prolonged washing of the membrane by an aqueous solution on both sides and by protein contained solutions on the blood side which removes some substance from the membrane which affects leucocytes directly or by activation of complement. A series of studies to test this hypothesis were performed using two hemodialysis membranes -Cuprophan (Enka AG) and Cellulate (Cordis Dow Corporation) and the results obtained demonstrate no elution of any water soluble substance from the dialyser membrane.

Humans↗
PubMed1975

Edgar John Rouse.

Explore the source record for details and available documents.

Australia↗
PubMedDate not supplied

Biochemical basis of the beta-glucuronidase gene defect causing canine mucopolysaccharidosis VII.

Mucopolysaccharidosis type VII (MPS VII), or Sly syndrome, is an autosomal recessive lysosomal storage disorder resulting from the deficiency in the activity of the enzyme beta-glucuronidase (GUSB). To characterize the biochemical and molecular defect in GUSB-deficient MPS VII dogs, we have measured lysosomal enzyme activities, analyzed distribution of glycosaminoglycans (GAGs), and estimated the size and abundance of the GUSB gene product at the mRNA and protein level in normal, homozygous affected, and heterozygous carrier retinal pigment epithelium (RPE) samples. Compared to normal, only 2-5% and 40-60% of GUSB activity was detected in the affected and the carrier samples, respectively. The decrease in GUSB activity resulted in storage of GAGs predominantly heparan sulfate and chondroitin sulfate. A slight increase in storage of GAGs was also observed in the carrier sample. Northern blot analysis of affected and carrier RPE samples detected a 2.4 kb GUSB transcript similar in size and abundance to that of normal controls. In western blot analysis using anti-human GUSB antibody, three bands of size 78, 56, and 38 kDa were detected in normal samples, which were present at lower intensity in the carrier RPE samples and absent in the MPS VII-affected RPE samples. These results suggest that the mutant GUSB gene causes a posttranscriptional defect and produces an unstable protein.

Aged↗