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J H Wilson

Publications and source records attributed to J H Wilson.

At least 181 records · Page 10Linked to original sources
PubMed1990

Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene are responsible for acute intermittent porphyria.

Two mutations of the porphobilinogen (PBG) deaminase gene resulting in cross-reacting immunological material (CRIM) positive forms of acute intermittent porphyria (AIP) have been identified by in vitro amplification of cDNA and cloning of the amplified products in a bacterial expression vector. Both mutations resulted from G to A transitions in exon 10 of the gene and produced arginine to glutamine substitutions in the abnormal protein. Expression of mutant cDNA in Escherichia coli reveals that one but not the other of these amino acid changes results in a striking decrease of the optimal pH of the mutated enzyme. One or the other of these two mutations accounted for the defect causing AIP in six unrelated patients among the eight patients evaluated with the CRIM positive subtype of this disorder.

Acute Disease↗
PubMed1990

Erythrocyte porphobilinogen deaminase activity in porphyria cutanea tarda.

Porphyria cutanea tarda (PCT) results from a metabolic block in heme synthesis at the level of uroporphyrinogen decarboxylase. We measured the activity of one of the enzymes preceding it in the heme biosynthetic pathway, porphobilinogen deaminase (PBGD; EC 4.3.1.8), in erythrocytes of 47 patients with symptomatic or asymptomatic familial or sporadic PCT. PBGD activity was significantly increased in all four PCT groups, compared with controls. To study the mechanism of this increased PBGD activity, we determined, using polyclonal antibodies, the amount of immuno-detectable PBGD per 100 units of PBGD activity (Ig PBGD/100 U) and the total amount of immuno-detectable PBGD (Ig PBGD) in erythrocytes from all 47 patients and from controls. In both familial and sporadic PCT, Ig PBGD/100 U was decreased compared with that in controls (P less than 0.05). Especially in asymptomatic patients of the familial PCT group there was an inverse correlation between increasing PBGD activity and Ig PBGD/100 U (r = -0.90). In familial PCT, and to a minor degree in sporadic PCT, an increase in PBGD activity was accompanied by an increased Ig PBGD, compared with controls (familial PCT: P less than 0.001, sporadic PCT: P less than 0.05). In familial and sporadic PCT an increase in erythrocyte PBGD activity can, at least partly, be explained by a diminished degradation of PBGD. In familial PCT, in the symptomatic group more than in the asymptomatic group, and to a minor degree in sporadic PCT, there is in addition an increase in the absolute amount of PBGD.

Adult↗
PubMed1989

[A family study of the initial Dutch patients with porphyria].

The families of three porphyric patients originally described by Prof. Dr. A.A. Hijmans van den Bergh in the 1920s and of one porphyric patient described by Prof. Dr. I. Snapper in 1920 were traced and investigated to determine the type of the hereditary porphyria in each family. It was possible to confirm that Hijmans van den Bergh and coworkers had described hereditary coproporphyria and variegate porphyria. These were the first descriptions of these types of porphyria. The patient described by Snapper had acute intermittent porphyria.

Adult↗
PubMed1989

[The porphyrias].

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Acute Disease↗
PubMed1989

Differential effects of malotilate on 5-, 12- and 15-lipoxygenase in human ascites cells.

Macrophages isolated from fluids of patients with liver cirrhosis mainly generated the 5-lipoxygenase products leukotriene B4 and 5-monohydroxyeicosatetraenoic acid. The cyclooxygenase products 6-keto-PGF1 alpha and thromboxane B2 were the most important prostaglandin-like substances. Malotilate, an anti-fibrotic substance, selectively inhibited the 5-lipoxygenase, whereas both the 12- and the 15-lipoxygenase pathways were stimulated. The effects of malotilate on eicosanoid production differ from those of known lipoxygenase inhibitors. Such differential effects have not been reported previously.

Arachidonate 12-Lipoxygenase↗
PubMed1989

Effects of nicks on repair of single-stranded loops in heteroduplex DNA in mammalian cells.

Heteroduplexes that contain single-stranded loops are repaired very efficiently in mammalian cells. The strand that does not contain the loop is used as the template strand for repair nearly twice as often as the looped strand. In this study we tested the influence of nearby nicks on the choice of template strand. We find that strand selection in repair of heteroduplexes with single-stranded loops is influenced by the presence of a nick located 71 or 125 base pairs from the loop, but only to a minor degree. Thus the loop itself is a stronger signal for repair than is a nearby nick. On the other hand, if a break is introduced into the single strand that forms the loop, the looped strand is marked for excision and rarely, if ever, is used as the template for repair.

Animals↗
PubMed1989

Inhibition of the nuclear localization of [3H]estradiol in rat uterine tissue in vitro.

The temperature coefficient (Q10) for the nuclear-cytoplasmic intracellular distribution of specifically-bound [3H]estradiol is approximately 1.0 over the interval 10-30 degrees C. However, this value increases to 3.19 for the temperature influence upon the nuclear-cytoplasmic localization of hormone between 30 degrees and 37 degrees C. A Q10 value of this magnitude is indicative of a biological, rather than physical, translocation event. In assessment of a biological basis for translocation, several antimicrotubular/antimicrofilamentous agents were used alone and in combination to ascertain their effects upon in vitro nuclear localization of labeled estradiol in the uterus. The incubation of uterine tissue in D2O-Locke-Ringer's solution containing 10(-4) M colchicine or vinblastine significantly reduced the nuclear localization of [3H]estradiol to nonspecific retention. Tissue uptake of the hormone, cytoplasmic binding and retention of estrogen, and the nucleophilic property of the receptor-estrogen complex (REC) were unaffected. Other drug treatments were without effect upon nuclear occupancy of the REC. The apparent inhibition of translocation by the above regimen could be due to an alteration in cellular architecture incompatible with hormone movement or the result of a direct effect upon cellular components which impede the dynamic interactions of REC in nuclei of whole tissue. Although these results do not necessarily imply that a functional cytoskeleton is required for translocation, we suggest that the estrogen-mediated nuclear occupancy of REC is a biological process susceptible to disruption.

Animals↗
PubMed1989

Primary cells and established cell lines join DNA ends with the same efficiency relative to homologous recombination.

The joining of DNA ends was compared in the established CV1 cell line and in African green monkey kidney primary cells, from which the CV1 cell line was established. Using a linear SV40 genome that carries a terminal repeat of 526 nucleotide pairs, we measured the efficiency of circularization by end joining relative to circularization by homologous recombination between the terminal repeats. The ratios of end joining to homologous recombination were identical in the two types of cells regardless of whether the DNA ends were sticky, blunt, or mismatched. These studies demonstrate that the efficient end joining observed in established cell lines is not a peculiar adaptation to life in culture, but rather reflects a normal aspect of DNA metabolism in mammalian cells. Furthermore, the similar results in primary and established cells support the general validity of using data from studies of cultured cells to formulate models of recombinational processes in primary cells and potentially in multicellular organisms as well.

Animals↗
PubMed1989

A computer aid for early diagnostic classification of jaundice (the COMIP program).

We describe the Computer Icterus Program (COMIP), a computer-assisted diagnosis (CAD) program which is designed to facilitate the early choice of a diagnostic strategy in cases of jaundice. To anticipate transfer to other centres, the COMIP program offers facilities to make local adjustments for relative disease incidences and for laboratory data. This is a useful extension for CAD systems.

Algorithms↗
PubMed1989

Development of hexachlorobenzene porphyria in rats: time sequence and relationship with lipid peroxidation.

The relationship between the development of porphyria and free-radical formation induced by hexachlorobenzene was studied in iron-overloaded rats. The first sign of porphyria, an increase in porphyrins in the liver, was detected at day 22. Liver malondialdehyde was also increased at day 22. During the following weeks, liver porphyrins and malondialdehyde increased simultaneously, accompanied by a decrease in uroporphyrinogen decarboxylase activity and glucose-6-phosphate activity in liver, and a high excretion of porphyrins in the urine. In the rats given hexachlorobenzene, changes were detected in the pattern of lipids in the liver microsomes. In comparison with the controls, there were decreases in C20:4 and C22:5 fatty acids, whereas the fatty acid C20:3w6 was increased. In this study of hexachlorobenzene-induced liver damage there was no difference in the time course of the development of porphyria and that of lipid peroxidation.

Animals↗
PubMed1989

Targeted homologous recombination at the endogenous adenine phosphoribosyltransferase locus in Chinese hamster cells.

We have developed a system that permits analysis of targeted homologous recombination at an endogenous, chromosomal gene locus in cultured mammalian cells. Using a hemizygous, adenine phosphoribosyltransferase (APRT)-deficient, Chinese hamster ovary (CHO) cell mutant as a transfection recipient, we have demonstrated correction of a nonrevertible deletion mutation by targeted homologous recombination. Transfection with a plasmid carrying a fragment of the APRT gene yielded APRT+ recombinants at a frequency of approximately 4.1 x 10(-7). The ratio of targeted recombination to nontargeted integrations of plasmid sequences was approximately 1:4000. Analysis of 31 independent APRT+ recombinants revealed conversions of the endogenous APRT gene, targeted integration at the APRT locus, and a third class of events in which the plasmid donor APRT fragment was converted to a full-length, functional gene.

Adenine Phosphoribosyltransferase↗
PubMed1989

Tissue-specific splicing mutation in acute intermittent porphyria.

An inherited deficiency of porphobilinogen deaminase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] in humans is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease. It was previously demonstrated that porphobilinogen deaminase is encoded by two distinct mRNA species expressed in a tissue-specific manner. Analysis of the genomic sequences indicated that these two mRNAs are transcribed from two promoters and only differ in their first exon. The first mutation identified in the human porphobilinogen deaminase gene is a single-base substitution (G----A) in the canonical 5' splice donor site of intron 1. This mutation leads to a particular subtype of acute intermittent porphyria characterized by the restriction of the enzymatic defect to nonerythropoietic tissues. Hybridization analysis using oligonucleotide probes after in vitro amplification of genomic DNA offers another possibility of detecting asymptomatic carriers of the mutation in affected families.

Acute Disease↗
PubMed1989

Effects of the glucosidase inhibitor acarbose in patients with liver cirrhosis.

In this preliminary study, we examined the effects of acarbose and placebo together with a standardized breakfast on blood glucose levels, on breath hydrogen excretion and on plasma insulin and glucagon levels; in addition, the effects on fasting blood levels of metabolites were studied following an evening meal with acarbose or placebo. Acarbose significantly reduced blood glucose levels in 10 patients with alcoholic cirrhosis following a meal containing 100 g of carbohydrate. There were no significant changes in plasma insulin after breakfast but glucagon levels were increased at 1 h after the meal. Breath hydrogen excretion did not change significantly. Acarbose given with a late evening snack reduced fasting beta-hydroxybutyrate levels the next morning in these cirrhotic patients.

Acarbose↗
PubMed1989

Undersensing of P waves in the presence of an adequate P wave due to automatic postventricular atrial refractory period extension.

Two cases in which a DDD pacemaker failed to track P waves due to repetitive activation of the automatic postventricular atrial refractory period (PVARP) extension are reported. In one case, the cycle was initiated by a premature ventricular contraction (PVC); in the other, by touching the unipolar pacemaker with a needle while suturing. We demonstrated that chest wall stimulation can be used to induce cycles of repetitive automatic PVARP extension and failure to track P waves. We demonstrated in vitro that touching a unipolar pacemaker with a needle can generate a signal sufficient to mimic a QRS complex, and initiate a cycle of repetitive P wave undersensing.

Aged↗