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Biomedical subjects

J H Wilson

Publications and source records attributed to J H Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1996

Nicotine inhibits the in vitro production of interleukin 2 and tumour necrosis factor-alpha by human mononuclear cells.

Smoking protects against ulcerative colitis (UC), and treatment with nicotine patches has a beneficial symptomatic effect in patients with UC. To find an explanation for this response to nicotine in UC, we assessed the effects of nicotine on cytokine production by mononuclear cells (MNC). MNC were isolated from peripheral blood from healthy volunteers. Non-adherent MNC were preincubated with varying concentrations of nicotine or prednisolone for 24 h followed by addition of phytohemagglutinin (10 micrograms/ml). The concentrations of interleukin 2 (IL-2) and tumour necrosis factor-alpha (TNF alpha) in the supernatants were determined by ELISA. Nicotine as well as prednisolone caused a significant inhibition of IL-2 and TNF alpha production. The maximum inhibition caused by nicotine was about 50% of that caused by prednisolone and was reached at concentrations equivalent to nicotine levels measured in plasma of smokers. These results indicate that nicotine exerts its immunoregulatory role through modulation of the cytokine production by non-adherent mononuclear cells.

Cells, Cultured↗
PubMed1996

Drug-associated anaphylaxis: 20 years of reporting in The Netherlands (1974-1994) and review of the literature.

BACKGROUND: Since 1963, the Drug Safety Unit of the Dutch Inspectorate for Health Care (DSU) holds a voluntary reporting system. OBJECTIVE: To analyse all reports received in the years 1974 to 1994, registered as anaphylaxis or as a diagnosis that could contain cases of anaphylaxis. METHODS: All reports were classified as probable or possible anaphylaxis according to previously described criteria and the causal relationship between exposure and anaphylaxis was assessed. RESULTS: Nine hundred and ninety-two reports possibly concerning anaphylaxis were received between 1974 and 1994. Fifty-six were unclassifiable. The remaining 936 reports concerned 326 men and 610 women. Three hundred and forty-five reports were classified as anaphylaxis probable, 485 as anaphylaxis possible, and 106 as anaphylaxis unlikely by previously specified criteria. Drugs frequently associated with anaphylaxis (causal relationship certain or probable) were: glafenine (326 reports classified as anaphylaxis probable or possible), combination preparations with (propy)phenazone or propyphenazone/phenacetine (39), diclofenac (30), dextran (20), ibuprofen (14), floctafenine (12), allergen extracts (12), sulfamethoxazole with trimethoprim (12), and trimethoprim (11). There is probably substantial under-reporting as well as reporting bias in these data. Furthermore, many reports were classified as possible and not as probable anaphylaxis because the temporal relationship was unknown or not reported. CONCLUSION: Drugs that caused anaphylaxis most frequently were glafenine, NSAID and certain antibiotics. Data from a voluntary reporting system such as the DSU are valuable as an early warning system for drugs that may induce anaphylactic reactions.

Adult↗
PubMed1996

Effects of dietary boron supplementation on laying hens.

1. The effects of dietary boron on egg production and on the ultimate shear force, stress, and fracture energy of the tibia, femur, humerus, and radius from White Leghorn laying hens were investigated. 2. The shear force, stress, and fracture energy of the bones were not affected by increasing dietary concentrations of boron. 3. Egg production, food consumption and body weight were suppressed at a dietary boron concentration of 400 mg/kg. 4. Boron concentrations increased significantly in all tissue samples tested in birds given 400 mg/kg dietary boron.

Analysis of Variance↗
PubMed1996

In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells.

OBJECTIVE: Ulcerative colitis (UC) is predominantly a disease of non-smokers and treatment with transdermal nicotine improves symptoms in UC patients, whereas smoking seems to have a deleterious effect in patients with Crohn's disease (CD). In CD the cytokine profile is of a dominant TH1 (T helper 1) pattern whereas in UC the TH2 pattern predominates. To find an explanation for the beneficial effect of nicotine in UC and the deteriorative effect in CD we studied the in-vivo effect of nicotine on the interleukin 2 (IL-2), IL-10 and tumour necrosis factor alpha (TNF alpha) production by human cells. DESIGN: Eleven healthy male non-smokers were included in this study. The volunteers applied nicotine patches with a regulated release of 5 mg (day 1 and 2), 10 mg (day 3 and 4) and 15 mg (day 5, 6 and 7) nicotine per day. METHODS: Heart rate and blood pressure were recorded, nicotine and cotinine concentrations in plasma measured before and after 2, 4 and 7 days of treatment. Non-adherent mononuclear cells (NAC) were isolated from peripheral blood obtained from the subjects before and after 7 days of treatment. The NAC were cultured in the absence or presence of phytohemagglutinin for 48 h. Total amount of IL-2, IL-10 and TNF alpha formed were measured in the supernatants using specific ELISAs. RESULTS: Treatment with nicotine caused a significant inhibition of IL-10 production by NAC. In contrast, nicotine patch treatment had no effect on the production of IL-2 and TNF alpha. CONCLUSIONS: Nicotine in vivo has an inhibitory effect on TH2 cell function as measured by inhibition of IL-10 production, but does not appear to have any effect on TH1 cell function.

Adult↗
PubMed1996

Impedance of pacemaker leads: correlation of different methods.

This study compares three different pacing system analyzers, which measure impedance at different points during an impulse, with measurements telemetered from implanted pacemakers from four different manufacturers. Measurements were obtained at the time of implantation in a group of 103 patients. The measurements obtained by these different methods differ significantly from each other; the later during the impulse the impedance is measured, the higher in general its value. Interpretation of impedance values should take into account the technique of measurement.

Cardiac Pacing, Artificial↗
PubMed1996

High-frequency illegitimate integration of transfected DNA at preintegrated target sites in a mammalian genome.

To examine the mechanisms of recombination governing the illegitimate integration of transfected DNA into a mammalian genome, we developed a cell system that selects for integration events in defined genomic regions. Cell lines with chromosomal copies of the 3' portion of the adenine phosphoribosyltransferase (APRT) gene (targets) were established. The 5' portion of the APRT gene, which has no homology to the integrated 3' portion, was then electroporated into the target cell lines, and selection for APRT gene function was applied. The reconstruction of the APRT gene was detected at frequencies ranging from less than 10(-7) to 10(-6) per electroporated cell. Twenty-seven junction sequences between the integrated 5' APRT and its chromosomal target were analyzed. They were found to be randomly distributed in a 2-kb region immediately in front of the 3' portion of the APRT gene. The junctions fell into two main classes: those with short homologies (microhomologies) and those with inserted DNA of uncertain origin. Three long inserts were shown to preexist elsewhere in the genome. Reconstructed cell lines were analyzed for rearrangements at the target site by Southern blotting; a variety of simple and complex rearrangements were detected. Similar analysis of individual clones of the parental cell lines revealed analogous types of rearrangement, indicating that the target sites are unstable. Given the high frequency of integration events at these sites, we speculate that transfected DNA may preferentially integrate at unstable mammalian loci. The results are discussed in relation to possible mechanisms of DNA integration.

Adenine Phosphoribosyltransferase↗
PubMed1996

Effectiveness of Natuphos phytase in improving the bioavailabilities of phosphorus and other nutrients in soybean meal-based semipurified diets for young pigs.

Crossbred pigs (n = 96, BW = 7.5 kg) were used in a 5-wk trial to determine the effectiveness of supplemental Natuphos phytase in improving the bioavailabilities of P and other nutrients in a semipurified diet with soybean meal as the only P source in the basal diet. Two available P (aP) levels (.05 and .16%) and five phytase levels (0, 350, 700, 1,050, and 1,400 units/kg of diet) were used in a 2 x 5 factorial arrangement of treatments. In addition to the 10 diets, two extra diets were formulated to supply the recommended level of aP (.32%) with 0 and 1,400 units (U) of phytase/kg of diet. Graded levels of phytase resulted in linear increases in ADG (P < .02), ADFI (P < .01 at .16% aP only), and gain:feed ratio (P < .03). Effects of adding phytase to the diet with .32% aP were observed only in the first 14 d of the study with increases in ADG (P < .06) and gain:feed (P < .02) for added phytase. Apparent digestibility (or absorption) coefficients (ADC) of DM, P, Ca, and N were estimated using chromic oxide as an indicator during wk 4 and 5. When phytase and P were added to the low P diet, the ADC of P was increased (P < .01), but only small and variable changes in the ADC of DM, Ca, and N were observed. Fecal P excretion (grams per day) decreased as microbial phytase was added (P < .01) and increased with added P (P < .01). In comparison to the results with the .32% aP diet, fecal P excretion decreased 25 to 50% by the addition of phytase. The addition of phytase to the diet with .32% aP further improved (P < .01) the ADC of P (54.5 vs 61.8%) and decreased (P < .01) fecal P excretion (1.62 vs 1.38 g/d). Characteristics of 4th metacarpals and 10th ribs were consistently improved by increasing dietary levels of both phytase and P. On the basis of an assessment of R2 values from secondorder translog equations, ADG, ADFI, P apparent absorption, bone ash percentage, and bone shear force were sensitive indicators to evaluate phytase efficacy of P availability in diets. Phosphorus equivalency of microbial phytase was calculated by using response equations for ADG and apparent P absorption. The average function of the release of P (Y, grams per kilograms) by microbial phytase (X, units per kilogram of diet) was developed with aP levels of .05 and .16%: Y = 1.546-1.504e-.0015X. The replacement of 1 g of inorganic P would require about 676 U of microbial phytase. This represents 77% of released P from phytate.

6-Phytase↗
PubMed1996

Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris.

Elevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz, the acute phase reaction, total fibrin plus fibrinogen degradation (TDP) levels and the polymorphisms of the fibrinogen beta-gene. The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers, selected on genotype of the Bcl] polymorphism of the fibrinogen beta-gene, and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study. Functional plasma fibrinogen levels were measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP) and TDP levels were measured using an enzyme immuno assay (EIA). In the healthy volunteers the functional fibrinogen levels had decreased by 0.20 g/l (9%, p = 0.005 using the paired Student l-test) after 4 weeks of 250 mg bid ticlopidine administration, whereas fibrinogen antigen, CRP and TDP levels were not significantly changed. In the stable angina pectoris patients the pre-treatment fibrinogen, CRP and TDP levels were significantly higher than in the volunteer group. After four weeks 250 mg bid ticlopidine administration the functional fibrinogen levels had decreased by 0.38 g/l (11%, p < 0.005), whereas the fibrinogen antigen, CRP and TDP levels were not significantly changed. The levels of functional and antigen fibrinogen, CRP and TDP did not change significantly during the placebo period in the volunteers or the patients. Neither in the volunteers nor in the patients was the effect of ticlopidine on the fibrinogen levels associated with the fibrinogen beta-gene polymorphisms. Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation of the functionality of the molecule and unlikely to be modulated by the acute phase reaction, TDP-levels or the fibrinogen beta-gene polymorphisms.

Adult↗
PubMed1995

High-affinity triple helix formation by synthetic oligonucleotides at a site within a selectable mammalian gene.

Specific recognition of duplex DNA by a single-stranded oligonucleotide via the formation of triplex DNA is a rational approach for targeting specific regions of a genome. By screening a number of potential target sites for triple helix formation within mammalian genes that allow genetic selection in cell culture, we have identified a site within intron 1 of the hamster adenine phosphoribosyltransferase (APRT) gene that specifically binds a triplex-forming oligodeoxyribonucleotide (TFO) with high affinity. Under optimal conditions for triplex formation, the equilibrium dissociation constant is in the nanomolar range (Kd = 7 x 10(-10) M). This high-affinity binding is very specific, as a 10(5)-fold excess of genomic DNA reduced triplex formation less than 10-fold, and within a 6928-bp plasmid bearing the APRT gene, only restriction fragments containing the intron 1 site were found to bind the TFO. Results of DNase I protection assays were consistent with the TFO binding in an antiparallel orientation via reverse Hoogsteen hydrogen bonds in the major groove of the duplex. We have examined the kinetics of triplex formation as well as the effects of ionic composition and chemical modifications of the TFO on triplex formation. While divalent cations were not required for triplex formation, Mg2+ stabilized the triplex apparently through inhibition of TFO dissociation, with a mean bound lifetime of > 17 h for the triplex at Mg2+ concentrations above 5 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Phosphoribosyltransferase↗
PubMed1995

Efficient modification of the APRT gene by FLP/FRT site-specific targeting.

The FLP/FRT site-specific recombination system was established and characterized at the APRT gene in CHO cells. Targeting frequencies with FLP-stimulation were about 1 to 5 X 10(-5), which were 6-22-fold above gene targeting frequencies in the absence of FLP. Fifty two APRT+ cell lines were analyzed by Southern blotting: 56% were FLP-targeted integrants; 33% were APRT target convertants; 11% gave undefined patterns. In separate experiments we first enriched for integrants by screening for two additional markers carried on the targeting vector; 18 of 19 (95%) of the resulting cell lines were integrants. Intrachromosomal site-specific recombination was tested by reexposing integrants to FLP. Intrachromosomal popouts were stimulated over 200-fold, while homologous recombination in an adjacent interval was unchanged. The utility of this system was demonstrated by one-step FLP targeting to generate chromosomal substrates for homologous recombination, and by a two-step, FLP-and-run procedure to construct a chromosomal substrate for illegitimate recombination.

Adenine Phosphoribosyltransferase↗
PubMed1995

Levels of soluble intercellular adhesion molecule 1, eicosanoids and cytokines in ascites of patients with liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis.

The levels of the eicosanoids leukotriene B4, prostaglandin E2, prostacycline and thromboxane B2, the cytokines interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and soluble intercellular adhesion molecule 1 were measured in ascites and plasma samples of patients with liver cirrhosis (53), peritoneal cancer (26) and spontaneous bacterial peritonitis (10) to assess their value as a possible diagnostic and prognostic parameter in the course of the disease. Soluble intercellular adhesion molecule 1, of the eicosanoids prostaglandin E2 and leukotriene B4, and the protein concentration in ascites were all significantly elevated in ascites of patients with peritoneal cancer in comparison to ascites of patients with liver cirrhosis. In ascites of patients with spontaneous bacterial infection interleukin-6 concentration was significantly elevated and the protein concentration was significantly lower in comparison to the other two groups. None of these parameters, however, seems to be of practical use as a diagnostic parameter, as there is an overlap between all the levels of these mediators in ascites of liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis group. Soluble intercellular adhesion molecule 1 levels were much higher in plasma than in ascites, in contrast to interleukin-6 levels which were much higher in ascites than in plasma. Soluble intercellular adhesion molecule 1 in ascites correlated with soluble intercellular adhesion molecule 1 in plasma (r = 0.6926, P = 0.0001). Soluble intercellular adhesion molecule 1, interleukin-6 and the number of polymorphonuclear cells in peritoneal fluid correlated during episodes of infection in patients with a peritonitis. For this reason soluble intercellular adhesion molecule 1 and interleukin-6 could be of prognostic value for patients with peritonitis.

Adult↗
PubMed1995

Adjuvant intraoperative photodynamic therapy diminishes the rate of local recurrence in a rat mammary tumour model.

The use of photodynamic therapy (PDT) as an adjunct to curative tumour resection was investigated in a tumour recurrence model, using rat mammary adenocarcinoma BN472. Tumours were inoculated subcutaneously in 60 animals and resected after 21 days of growth. Immediately after removal, the operation site was exposed to 320-450 nm light of 0.1 W cm-2 and 60 J cm-2 after photosensitisation with either Photofrin (5 mg kg-1 i.v. 48 h before illumination) or 5-aminolaevulinic acid (ALA) (2 mg ml-1 in drinking water for 9 days). Porphyrin concentrations were measured in tissue samples. After 28 days, animals treated with adjunctive PDT had a significantly longer tumour-free interval than controls (P < 0.01); median 25 days (Photofrin), 18 days (ALA), 14 days (controls). Moreover, in the PDT groups significantly fewer rats had lymph node metastasis. A prophyrin concentration ratio between tumour and mammary tissue of 2:1 was found after Photofrin and 4:1 after ALA. The results indicate that adjuvant intraoperative PDT may be a safe and effective method of destroying residual tumour, thereby preventing locoregional tumour recurrence.

Adenocarcinoma↗
PubMed1995

High interleukin-6 production within the peritoneal cavity in decompensated cirrhosis and malignancy-related ascites.

To assess the diagnostic and prognostic value of interleukin-6, interleukin 1 beta, and tumor necrosis factor-alpha assays in plasma and ascites, we measured these cytokines in eight patients with malignancy-related ascites and 32 patients with decompensated cirrhosis. Five patients had an episode of bacterial peritonitis, during which one or more ascitic fluid samples were analyzed. Interleukin-6 and tumor necrosis factor-alpha were not significantly different between the cirrhotic and the malignant groups: ascitic interleukin-6 13,816 +/- 15,314 vs 28,138 +/- 23,403 pg/ml, plasma interleukin-6 542 +/- 719 vs 559 +/- 604 pg/ml; ascitic tumor necrosis factor-alpha 19 +/- 50 vs 12 +/- 31 pg/ml, plasma tumor necrosis factor-alpha 3.4 +/- 8.2 vs 6.1 +/- 13.8 pg/ml. During an episode of bacterial peritonitis there was a significant increase only in ascitic interleukin-6 (133,268 +/- 99,743 pg/ml), which declined after antibiotic treatment. None of the parameters was associated with 6-month survival (11 of the 40 patients died within 6 months). There was a correlation (r = 0.675; p = 0.002) between plasma interleukin-6 levels and the Child-Pugh score in patients with cirrhosis, but not with the etiology of the liver disorder. Plasma interleukin-6 levels correlated with IgA levels (r = 0.649; p = 0.004) but not with C reactive protein, sedimentation rate, fibrinogen, IgM or IgG. These results do suggest that interleukin-6 is produced within the peritoneal cavity in hepatic and malignant ascites. There is a sharp increase in the local production of interleukin-6 during an episode of bacterial peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Heme synthesis in chronic renal failure: the effects of hemodialysis, peritoneal dialysis and erythropoietin treatment.

UNLABELLED: Increased plasma porphyrins have been described in patients with chronic renal failure (CRF). We measured plasma levels of porphyrins and the activity in erythrocytes of porphobilinogen deaminase (PBG-D), one of the key enzymes in heme biosynthesis, in CRF patients not yet on dialysis and in patients on intermittent hemodialysis (IHD) or chronic ambulatory peritoneal dialysis (CAPD), some of whom were being treated with recombinant human erythropoietin (rHuEPO). In addition, the amount of immuno-detectable PBG-D (Ig PBG-D) per 100 units standard PBG-D activity (Ig PBG-D/100 U) and the total amount of Ig PBG-D, using polyclonal antibodies, were determined in erythrocytes of all patients and controls to detect changes in biodegradation of this enzyme. Plasma porphyrins were increased in CRF patients not yet on dialysis and even higher in both patient groups on dialysis compared with controls. Plasma porphyrins were higher in patients on IHD than in patients on CAPD. The activity of PBG-D was increased and Ig PBG-D/100 U was decreased in patients on IHD compared with CRF patients not yet on dialysis and patients on CAPD. Reticulocyte counts were also greater in patients on IHD than in CRF patients not yet on dialysis and patients on CAPD. Ig PBG-D was increased in both groups of patients on dialysis and treated with rHuEPO compared with patients not treated with rHuEPO. IN CONCLUSION: (1) in patients on IHD, an increased production of porphyrins is, at least partly, caused by an increased PBG-D activity, and (2) an increased PBG-D activity and a decrease in Ig PBG-D/100 U in patients on IHD could be explained by the presence of a (relatively) young erythroid cell population in which a larger part of PBG-D has not yet been degraded.

Adult↗
PubMed1995

An evaluation of various response criteria in assessing biological availability of phosphorus for broilers.

The relative bioavailability of P from seven sources was determined in relation to a standard dicalcium phosphate dihydrate (CaHPO4.2H2O) in a 21-d assay involving 1,320 broiler male chicks using several response criteria. The seven sources (Lucaphos-48, Lucaphos-40, Rukana, Cefkaphos-N, phosphoric acid, monocalcium phosphate monohydrate, or Biophos) were added to the basal diet (.40% total P and 1.10% Ca) at levels to supply .05, .08, .12, .17, .23, and .32% P. Two additional levels (.44 and .66%) of P from dicalcium phosphate dihydrate were included for the standards. The criteria selected to evaluate included tibia ash, tibia specific gravity, tibia shear force, toe shear force, and metatarsal shear force. Other criteria: weight, length, diameter, and volume of tibia; weight, volume, and specific gravity of metatarsus; and weight, volume, and specific gravity of toe were not selected because their response to increasing P levels were inconsistent and quite variable. Nonlinear (asymptotic and sigmoidal) regression equations were fitted to the data than linear equations. The ratios of regression coefficients were used to determine the bioavailability of various test phosphates relative to the reference standard. The results indicated that the response criteria used for the determination will considerably influence the relative bioavailability estimates of a P source. Body weight gain and toe ash percentage were found to be an equally or a more sensitive criteria for assessment of P availability than tibia ash. Tibia specific gravity, tibia shear force, toe shear force, and metatarsal shear force were of limited value as response criteria in P bioavailability assays based on standard error and difference required for significance.

Animals↗