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Biomedical subjects

J H Wilson

Publications and source records attributed to J H Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus.

Administration of 5-aminolaevulinic acid (ALA) leads to porphyrin accumulation in malignant and premalignant tissues, and ALA is used as a prodrug in photodynamic therapy (PDT). To understand the mechanism of porphyrin accumulation after the administration of ALA and to investigate whether ALA-induced protoporphyrin IX might be a suitable photosensitizer in Barrett's oesophagus and adenocarcinoma, we determined the activities of porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) in various malignant and premalignant as well as in normal tissues of the human oesophagus. A PDT power index for ALA-induced porphyrin accumulation, the ratio of PBG-D to FC normalized for the normal squamous epithelium of the oesophagus, was calculated to evaluate intertissue variation in the ability to accumulate porphyrins. In malignant and premalignant tissue a twofold increased PBG-D activity and a marginally increased FC activity was seen compared with normal squamous epithelium. A significantly increased PDT power index in Barrett's epithelium and adenocarcinoma was found. Our results suggest that, after the administration of ALA, porphyrins will accumulate in a greater amount in Barrett's epithelium and adenocarcinoma of the oesophagus because of an imbalance between PBG-D and FC activities. The PDT power index here defined might be a useful indicative parameter for predicting the susceptibility of these tissues to ALA-PDT.

Adult↗
PubMed1998

Transdermal nicotine inhibits interleukin 2 synthesis by mononuclear cells derived from healthy volunteers.

BACKGROUND: Smoking has either a beneficial or harmful effect on the course and recurrence of ulcerative colitis (UC) and Crohn's disease respectively. Transdermal application of nicotine had similar effects in UC and therefore was considered to be an effective basic drug that could be further developed in the search for new compounds in the treatment of acute exacerbations of corticosteroid-resistant UC. To clarify the hypothesis that nicotine exerts its anti-inflammatory effect in UC through selective inhibition of T-cell-derived cytokine synthesis, we studied in vivo effects of nicotine on cytokine production by human non-adherent mononuclear cells isolated from peripheral blood in a randomized, double-blind, placebo-controlled trial. METHODS: Healthy non-smoking volunteers applied for 2 weeks of nicotine patches (n = 12) with incremental doses of nicotine during the first week to achieve a maintenance dose of 15 mg per day, or placebo (n = 12). Blood was obtained before treatment and 1, 2, 3 and 6 weeks after the start of treatment. Cells were cultured in the absence or presence of phytohaemagglutinin for 48 h, and total amounts of interleukin 2 (IL-2), IL-4, IL-10, IL-13, interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) were measured. RESULTS: Transdermal nicotine caused a significant inhibition of IL-2 after 2 weeks' treatment compared with the placebo group. In addition, a diminished production of IL-10 and TNF-alpha in comparison with day 0 was observed. CONCLUSION: The beneficial effect of transdermal nicotine in ulcerative colitis may be mediated by a selective inhibition of the IL-2 production by mucosal mononuclear cells, which could result in diminished cell proliferation and consequently a reduction in the inflammatory process.

Administration, Cutaneous↗
PubMed1998

Cross-linking sites of the human tau protein, probed by reactions with human transglutaminase.

A portion of the neurofibrillary tangles of Alzheimer's disease has the characteristics of cross-linked protein. Because the principal component of these lesions is the microtubule-associated protein tau, and because a major source of cross-linking activity within neurons is supplied by tissue transglutaminase (TGase), it has been postulated that isopeptide bond formation is a major posttranslational modification leading to the formation of insoluble neurofibrillary tangles. Here we have mapped the sites on two isoforms of human tau protein (tau23 and tau40) capable of participating in human TGase-mediated isopeptide bond formation. Using dansyl-labeled fluorescent probes, it was shown that eight Gln residues can function as amine acceptor residues, with two major sites being Gln351 and Gln424. In addition, 10 Lys residues were identified as amine donors, most of which are clustered adjacent to the microtubule-binding repeats of tau in regions known to be solvent accessible in filamentous tau. The distribution of amine donors correlated closely with that of Arg residues, suggesting a link between neighboring positive charge and the TGase selectivity for donor sites in the protein substrate. Apart from revealing the sites that can be cross-linked during the TGase-catalyzed assembly of tau filaments, the results suggest a topography for the tau monomers so assembled.

Amino Acid Sequence↗
PubMed1998

Long term effects of boron on layer bone strength and production parameters.

1. The effects of dietary boron (0, 50, 100, 200, and 400 mg/kg) on bone strength characteristics and egg production of white leghorn layers were investigated. 2. The shear fracture energy increased in the tibia and radius at 72 weeks for birds started on the 200 mg/kg supplement at 32 weeks of age. 3. The shear force, stress, and fracture energy of the tibia and radius increased for the non-egg producing birds at 72 weeks. 4. Bird body weight, food consumption, egg weight, and egg production all decreased at 400 mg/kg boron. 5. Boron concentrations in the breast, liver, thigh and bone tissue increased with increasing concentrations of supplemental boron.

Animal Feed↗
PubMed1998

Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis.

FRom several in vitro and in vivo studies involvement of somatostatin (SMS) in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 microg daily) or octreotide (3 microg daily) subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS) 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin-1beta (IL-1beta), IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity.

Animals↗
PubMed1997

Recombination-dependent deletion formation in mammalian cells deficient in the nucleotide excision repair gene ERCC1.

Nucleotide excision repair proteins have been implicated in genetic recombination by experiments in Saccharomyces cerevisiae and Drosophila melanogaster, but their role, if any, in mammalian cells is undefined. To investigate the role of the nucleotide excision repair gene ERCC1, the hamster homologue to the S. cerevisiae RADIO gene, we disabled the gene by targeted knockout. Partial tandem duplications of the adenine phosphoribosyltransferase (APRT) gene then were constructed at the endogenous APRT locus in ERCC1- and ERCC1+ cells. To detect the full spectrum of gene-altering events, we used a loss-of-function assay in which the parental APRT+ tandem duplication could give rise to APRT- cells by homologous recombination, gene rearrangement, or point mutation. Measurement of rates and analysis of individual APRT- products indicated that gene rearrangements (principally deletions) were increased at least 50-fold, whereas homologous recombination was affected little. The formation of deletions is not caused by a general effect of the ERCC1 deficiency on gene stability, because ERCC1- cell lines with a single wild-type copy of the APRT gene yielded no increase in deletions. Thus, deletion formation is dependent on the tandem duplication, and presumably the process of homologous recombination. Recombination-dependent deletion formation in ERCC1- cells is supported by a significant decrease in a particular class of crossover products that are thought to arise by repair of a heteroduplex intermediate in recombination. We suggest that the ERCC1 gene product in mammalian cells is involved in the processing of heteroduplex intermediates in recombination and that the misprocessed intermediates in ERCC1- cells are repaired by illegitimate recombination.

Adenine Phosphoribosyltransferase↗
PubMed1997

Hydrolysis of gamma:epsilon isopeptides by cytosolic transglutaminases and by coagulation factor XIIIa.

Nepsilon-(gamma-glutamyl)lysine cross-links, connecting various peptide chain segments, are frequently the major products in transglutaminase-catalyzed reactions. We have now investigated the effectiveness of these enzymes for hydrolyzing the gamma:epsilon linkage. Branched compounds were synthesized, in which the backbone on the gamma-side of the cross-bridge was labeled with a fluorophor (5-(dimethylamino)-1-naphthalenesulfonyl or 2-aminobenzoyl) attached through an epsilon-aminocaproyl linker in the N-terminal position, and the other branch of the bridge was constructed with Lys methylamide or diaminopentane blocked by 2,4-dinitrophenyl at the Nalpha position. Hydrolysis of the cross-link could be followed in these internally quenched substrates by an increase in fluorescence. In addition to the thrombin and Ca2+-activated human coagulation Factor XIIIa, cytosolic transglutaminases from human red cells and from guinea pig liver were tested. All three enzymes were found to display good isopeptidase activities, with Km values of 10(-4) to 10(-5) M. Inhibitors of transamidation were effective in blocking the hydrolysis by the enzymes, indicating that expression of isopeptidase activity did not require unusual protein conformations. We suggest that transglutaminases may play a dynamic role in biology not only by promoting the formation but also the breaking of Nepsilon-(gamma-glutamyl)lysine isopeptides.

Animals↗
PubMed1997

Effects of boron on growing pullets.

The effect of dietary boron on bone ash content and on the ultimate shear force, stress, and fracture energy of the tibia, femur, humerus, and radius from white Leghorn pullets were investigated. There was a significant increase in the shear force of the tibia and femur for pullets supplemented with 50 and 100 mg/kg of dietary boron. There was a significant increase in the shear stress of the tibia at 50 and 100 mg/kg of boron, and also an increase in shear fracture energy at 50 and 100 mg/kg boron for the femur. Tibia bone ash content increased significantly at 50, 100, and 200 mg/kg boron with the highest value at 50 mg/kg. Even though there was not a significant increase in body wt at 50 and 100 mg/kg boron, the pullets fed these supplements were consistently heavier than the control group.

Animals↗
PubMed1997

Drug-induced chest pain and myocardial infarction. Reports to a national centre and review of the literature.

OBJECTIVES: To analyse reports of drug-induced myocardial infarction and chest pain sent to a national reporting centre. To review which drugs were suspected of exhibiting these adverse events and what mechanisms were involved. METHODS: During the 20-year period 1975 through 1994, a total of 19,141 reports on adverse reactions to drugs were received by the Netherlands Centre for Monitoring of Adverse Reactions to Drugs. Of these 19,141 reports, 220 (1.1%) were concerned with drug-induced chest pain or myocardial infarction. After excluding reports in which the causal relationship was unlikely, poorly documented reports and reports on cases of overdosage, 183 reports (84%) were analysed. RESULTS: There were 130 reports (71%) of drug-induced chest pain and 53 reports (29%) of drug-induced myocardial infarction. A total of 104 reports concerned females (57%). The most frequently reported suspected drugs were the antimigraine drug sumatriptan (33 reports, 4 concerning myocardial infarction), the calcium antagonist nifedipin (9 reports, 2 of myocardial infarction) and nicotine [9 reports (8 patches, 1 chewing gum), 5 concerning myocardial infarction]. There were 18 reports of a fatal outcome. CONCLUSIONS: Several drugs can produce chest pain or myocardial ischaemia. It is important to recognise drugs as a potential cause, especially in patients with normal coronary arteries.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

Malignancy in Peutz-Jeghers syndrome? The pitfall of pseudo-invasion.

Peutz-Jeghers syndrome is a malignancy-associated polyposis syndrome. We describe a histopathologic phenomenon easily encountered when examining the nature of Peutz-Jeghers polyps but that is underreported in the literature. This phenomenon of "pseudo-invasion" may mimic invasive carcinoma due to epithelial displacement and erroneously give the impression, both macroscopically and microscopically, that a malignancy is involved. This potential pitfall is illustrated by the case of a patient with Peutz-Jeghers syndrome who was thought to harbor a metastasizing adenocarcinoma in his small bowel with peritoneal metastasis as a perioperative finding. Histologic examination, however, revealed pseudo-invasion.

Adult↗
PubMed1997

Repair of site-specific double-strand breaks in a mammalian chromosome by homologous and illegitimate recombination.

In mammalian cells, chromosomal double-strand breaks are efficiently repaired, yet little is known about the relative contributions of homologous recombination and illegitimate recombination in the repair process. In this study, we used a loss-of-function assay to assess the repair of double-strand breaks by homologous and illegitimate recombination. We have used a hamster cell line engineered by gene targeting to contain a tandem duplication of the native adenine phosphoribosyltransferase (APRT) gene with an I-SceI recognition site in the otherwise wild-type APRT+ copy of the gene. Site-specific double-strand breaks were induced by intracellular expression of I-SceI, a rare-cutting endonuclease from the yeast Saccharomyces cerevisiae. I-SceI cleavage stimulated homologous recombination about 100-fold; however, illegitimate recombination was stimulated more than 1,000-fold. These results suggest that illegitimate recombination is an important competing pathway with homologous recombination for chromosomal double-strand break repair in mammalian cells.

Adenine Phosphoribosyltransferase↗
PubMed1997

Peutz-Jeghers polyps, dysplasia, and K-ras codon 12 mutations.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant, polyposis syndrome, associated with an increased risk of gastrointestinal and extragastrointestinal malignancy. Occasionally dysplasia occurs in PJS polyps. AIMS: In colorectal carcinomas, mutations in codon 12 of the K-ras oncogene are common and are found at similar frequency in precursor adenomas. Therefore, K-ras codon 12 point mutations in PJS polyps, were evaluated. MATERIALS AND METHODS: Fifty two PJS polyps, including four with dysplasia, collected from 19 patients with PJS, were analysed for mutations in the K-ras codon 12 by a mutant enriched polymerase chain reaction procedure, followed by allele specific oligodeoxynucleotide hybridisation. RESULTS: A K-ras codon 12 mutation was identified, in one colonic polyp with dysplasia. The mutation was found in the non-neoplasmic epithelial cells and not in the dysplastic component of the polyp. CONCLUSIONS: K-ras codon 12 point mutations are very rare in PJS polyps, by contrast with colorectal adenomas. The findings support previous evidence that there seems to be no intrinsic relation between K-ras codon 12 mutation and dysplasia.

Autoradiography↗
PubMed1997

Prevention of colorectal cancer. Costs and effectiveness of sigmoidoscopy.

There is increasing evidence that endoscopic polypectomy is a very effective means of preventing colorectal cancer. The feasibility of population-wide endoscopic screening is not established, however. The appearance of adenomatosis around the age of 60 in one-third of the population, many years prior to the manifestation of significant numbers of colorectal cancers, and the observation that the risk of developing metachronous adenomas correlates with pre-existing numbers of adenomas per colon suggest that a baseline endoscopy at 60 years with minimal follow-up may be a feasible screening strategy with a high rate of primary prevention in average risk individuals. Projections were made of the costs and benefits of various scenarios. A key element of this analysis was the assessment of probabilities to develop metachronous adenomas as a function of prior adenoma status by a mathematical approach using autopsy data. A screening strategy consisting of a baseline sigmoidoscopy at 60 years with follow-up restricted to 6% of the population was estimated to prevent 50% of colorectal cancers occurring after 60 years. A range of alternative scenarios, giving rates of primary prevention of colorectal cancer from 40 to 70%, had costs which were comparable to those of breast-cancer screening, but was far superior considering effectivity.

Adenomatous Polyposis Coli↗
PubMed1996

High-efficiency triple-helix-mediated photo-cross-linking at a targeted site within a selectable mammalian gene.

Targeting damage to specific sites in the genome represents an attractive approach to manipulating gene function in mammalian cells. To test the applicability of triple-helix formation as a means for achieving precisely timed site-specific damage within a mammalian gene, a triplex-forming oligodeoxyribonucleotide (TFO) that binds with high affinity to a specific site within the hamster adenine phosphoribosyltransferase (APRT) gene was modified with the photochemically reactive psoralen derivative 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT). The modified TFO, psorTFO1, bound with high affinity to a target site within intron 1 of the APRT gene. Upon irradiation, photomonoadducts (i.e., covalent adducts of psorTFO1 to one strand of the target duplex) were formed with high efficiency (approximately 50%). Introduction of 5'-TpA sequences (the preferred site for psoralen-induced photo-cross-links) at or near the triplex junction leads to increased efficiency of total photoadduct formation and to efficient formation of products that had the electrophoretic mobility on denaturing PAGE expected for three-stranded photo-cross-links (i.e., products containing psorTFO1 covalently linked to both strands of the duplex). Their identities as cross-links were verified by (1) identical electrophoretic mobility of products formed with either duplex strand radiolabeled and (2) coprecipitation of the radiolabeled duplex strand with its complementary biotinylated strand following denaturation. In addition, the cross-links were completely reversible upon irradiation at 254 nm, as expected for psoralen-mediated cross-links. The yield and distribution of photoadducts depended on 5'-TpA position. The most efficient photoadduct formation (approximately 90%) and photo-cross-link formation (approximately 90% of total photoadducts) were observed for a 5'-TpA adjacent to the triplex junction, with significant, but lower, cross-linking efficiency within three base pairs of the junction. Molecular models of the psoralen-conjugated triplex with its six-carbon linker suggested a simple explanation for this distance dependence: facile intercalation near the triplex/duplex junction, with increasing strain required for intercalation at more distant sites. These results indicate that psorTFO1 allows for DNA damage with high precision and high efficiency, and the likely proportion of monoadducts and cross-links can be estimated from the target sequence.

Adenine Phosphoribosyltransferase↗
PubMed1996

Stimulation of intrachromosomal homologous recombination in human cells by electroporation with site-specific endonucleases.

In somatic mammalian cells, homologous recombination is a rare event. To study the effects of chromosomal breaks on frequency of homologous recombination, site-specific endonucleases were introduced into human cells by electroporation. Cell lines with a partial duplication within the HPRT (hypoxanthine phosphoribosyltransferase) gene were created through gene targeting. Homologous intrachromosomal recombination between the repeated regions of the gene can reconstruct a functioning, wild-type gene. Treatment of these cells with the restriction endonuclease Xba I, which has a recognition site within the repeated region of HPRT homology, increased the frequency or homologous recombination bv more than 10-fold. Recombination frequency was similarly increased by treatment with the rare-cutting yeast endonuclease PI-Sce I when a cleavage site was placed within the repeated region of HPRT. In contrast, four restriction enzymes that cut at positions either outside of the repeated regions or between them produced no change in recombination frequency. The results suggest that homologous recombination between intrachromosomal repeats can be specifically initiated by a double-strand break occurring within regions of homology, consistent with the predictions of a model.

Base Sequence↗
PubMed1996

The influence of a (GT)29 microsatellite sequence on homologous recombination in the hamster adenine phosphoribosyltransferase gene.

Several DNA sequence elements are thought to stimulate homologous recombination, illegitimate recombination, or both in mammalian cells. Some are implicated by their recurrence around rearrangement breakpoints, others by their effects on recombination of extrachromosomal plasmids. None of these sequences, however, has been tested on the chromosome in a defined context. In this paper we show how the adenine phosphoribosyltransferase locus in CHO cells can be used to study the recombinogenic potential of defined DNA sequences. As an example we have measured the effect on homologous recombination of a dinucleotide repeat, (GT)29, which has been shown to stimulate homologous recombination in extrachromosomal vectors 3-20 fold. On the chromosome at the adenine phosphoribosyltransferase locus, however, this sequence shows no capacity to stimulate recombination or to influence the distribution of recombination events.

Adenine Phosphoribosyltransferase↗
PubMed1996

Early postnatal alcohol exposure in rats: maternal behavior and estradiol levels.

Long Evans male and female rats were exposed to alcohol or control conditions during the early postnatal period, and their maternal behavior was assessed between 25 and 29 days of age. Maternal behavior was induced by exposing experimental animals to pups, and behaviors included retrieval of pups and proximity to pups. After 5 days of continuous exposure to pups, experimental animals were decapitated, and trunk blood was measured for levels of estradiol and progesterone. Alcohol-exposed animals showed a deficit in maternal behavior as measured by a longer latency to retrieve pups than rats that were not treated with alcohol. In addition, alcohol-exposed animals had lower levels of circulating estradiol than controls. These effects may also be explained by undernutrition as a result of artificial rearing. No difference in progesterone levels was found. As estradiol is important for the onset of maternal behavior in adult rats, it may be that the alcohol-induced decrease in estradiol levels underlies the deficit in maternal behavior exhibited by alcohol-exposed rats.

Animals↗