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Biomedical subjects

C Ekström

Publications and source records attributed to C Ekström.

15 recordsLinked to original sources

Exclusive measurement of the pp --> pppi(+)pi(-) reaction near threshold.

The pp-->pp pi(+) pi(-) reaction has been measured exclusively near threshold at CELSIUS. The total cross sections are nearly an order of magnitude lower than expected from previous inclusive measurements. The differential cross sections reveal pp-->pp(*)(1440)-->pp sigma = pp(pi(+)pi(-))(I = l = 0) as the dominant process as well as significant contributions from p(*)-->Delta(++)pi(-)-->psigma. The observed anisotropy in the proton angular dependence is consistent with heavy-meson exchange. In the invariant mass spectra, no narrow structures of statistical relevance (3sigma) are found.

Journal Article↗

GH is a regulator of IGF2 promoter-specific transcription in human liver.

The regulation of the insulin-like growth factor-II gene (IGF2) is complex and involves the usage of four promoters resulting in different 5' untranslated regions, but with a common translated product. The IGF2 gene product is a mitogenic and survival factor that has been suggested to be important for a normal fetal development and cancer. In this paper we present evidence suggesting that the human IGF2 gene is regulated by GH, and that this regulation occurs in a promoter-specific way. Three lines of evidence support this finding. First, in vivo data from patients treated with GH (one injection or daily injections for 5 consecutive days) showed an increase in the IGF2 P2 promoter derived transcript after acute treatment, and of the P4 promoter transcript after short-term treatment while the P1 promoter derived transcript did not show any significant change. Secondly, isolated human liver cells treated with GH for 2 h displayed an upregulation of the P2 promoter derived transcript. Thirdly, employing transfection experiments in GH-receptor positive CHO cells with P2 and P4 promoter-luciferase constructs, an upregulation by GH was evident, while a P1 promoter construct was unresponsive. We suggest that GH may be a physiological regulator of IGF2 in humans.

Analysis of Variance↗

Altered expression of members of the IGF-axis in hepatoblastomas.

Previous reports have demonstrated that expression of insulin-like growth factor 2 (IGF2) is altered in hepatoblastoma. Using RNAase protection analysis (RPA), we examined the gene expression for IGF1, IGF2, IGF1R, M6P/IGF2R, IGFBP-1 and IGFBP-2 in a series of hepatoblastomas with corresponding normal liver from the same individuals. The results show that the expression of the IGF-axis members included in the present study are altered between tumour and normal, and indicate that the IGF-axis may be involved in hepatoblastoma development.

Genes, Tumor Suppressor↗

Comparison of the sensitivities of Salmonella typhimurium strains TA102 and TA2638A to 16 mutagens.

The qualitative and quantitative sensitivity of the genetically related, histidine-auxtrophic Salmonella typhimurium strains TA102 and TA2638a to 16 compounds was examined. The compounds were mainly cross-linking and oxidising mutagens, the effects of which were known to be detected by strain TA102 preferentially or by a combination of Escherichia coli WP2 (pkM101) and uvrA/pkM101. The morphology and number of spontaneous revertants was also compared. Fourteen of the 16 compounds caused reversion in both strains. Bleomycin and streptomycin induced reversion in strain TA102 but not TA2638a. The greater sensitivity of TA102 to these compounds may be associated with the extrachromosomal location of the target genes. The overall quantitative sensitivity of the two strains was similar for the other compounds. The number of compounds that caused reversions at lower doses or produced greater proportional increases were the same in TA102 as in TA2638a. The spontaneous number of revertants, without and with metabolic activation, respectively, was 98 and 130 for TA2638a and 322 and 465 for TA102. Strain TA2638a formed larger, more uniform colonies than TA102. The present results together with those of previous studies indicate a high degree of concordance between the sensitivity of strains TA102 and TA2638 for the detection of mutagens. The uniform colony size and lower spontaneous reversion frequency seen with strain TA2638a compared with TA102 would make it more reliable and convenient for routine testing. It is concluded that strain TA2638a should be considered as an alternative to TA102 and included, as well as the two E.coli strains, in the set of bacterial strains used in the standard test battery for mutagenicity testing.

Animals↗

Acute and short-term effects of growth hormone on insulin-like growth factors and their binding proteins: serum levels and hepatic messenger ribonucleic acid responses in humans.

We investigated the acute (4-5 h) and short-term (5 days) effects of GH treatment on hepatic messenger RNA (mRNA) levels of the genes for the insulin-like growth factors (IGFs), insulin-like growth factor binding protein-1, -2, and -3 (IGFBPs), and the acid labile subunit (ALS), as well as serum levels of these proteins in humans. At the mRNA level, we observed an increase in IGF-1 transcription (+173%) following GH treatment in the acute group, which remained elevated in the short-term treatment group. IGFBP-2 mRNA decreased after short-term GH treatment, without changes in IGFBP-1 or -3 expression. The ALS transcript level increased after 5 days. In serum, we found increased levels of IGF-I and insulin, and decreased levels of IGF-II, in the short-term treatment group. IGFBP-1 decreased in both treatment groups, whereas IGFBP-2 was reduced after 5 days treatment. ALS increased in the short-term group. We observed increased IGFBP-3 serum levels after 5 days of GH treatment, likely due to increased formation of the ternary complex. Our results show that the metabolic effects by GH on the IGF axis are complex. In addition to a direct stimulation of IGF-I and ALS expression, GH inhibits IGFBP-1 serum levels and IGFBP-2 expression in an indirect manner, possibly facilitating enhanced IGF bioavailability to target tissues.

Adult↗

Disrupted IGF2 promoter control by silencing of promoter P1 in human hepatocellular carcinoma.

Previous investigations have supported or indicated a stimulatory role of the insulin-like growth factor II gene (IGF2) in hepatocarcinogenesis. We have studied the transcript levels, promoter usage, and imprinting status of the ICF2 gene and its relationship to H19 in human hepatocellular carcinomas (HCCs) and liver tumor cell lines. The activity of the IGF2 promoter P1 was lost in about 70% of the cases (18 of 25). This is the most prominent abnormality regarding the IGF2 regulation in this study. Total IGF2 as well as promoter P3 transcription were up-regulated in a small group of the tumors. Twenty genetically informative cases were obtained from 26 cases, thus excluding the probability of loss of heterozygosity of the IGF2 gene. Among these, nine showed abnormal monoallelic expression of IGF2. One HCC and one HCC cell line proved loss of functional imprinting of IGF2. H19 and IGF2 were regulated in parallel, and expression levels were variable. Taken together, the disruption of the IGF2 promoter regulation, particularly the loss of P1 activity, is a common feature of human HCCs. The loss of P1 activity explains the frequent loss of biallelic IGF2 expression and may potentially be used as a diagnostic or monitoring marker for human HCC.

Alleles↗

Prevalence of open-angle glaucoma in central Sweden. The Tierp Glaucoma Survey.

A population-based survey of 760 people 65-74 years of age was conducted in the municipality of Tierp, central Sweden. The methods used to identify glaucoma suspects were applanation tonometry, automatic perimetry (Competer 350), and binocular assessment of the optic disc. For a diagnosis of definite open-angle glaucoma, a visual field defect was required. Open-angle glaucoma was found at a prevalence of 5.70% (95% confidence interval: 4.12-7.27), which is higher than those figures reported for comparable surveys carried out on white populations. The occurrence of capsular glaucoma may in part explain this finding. Twenty of the 45 open-angle glaucomas were diagnosed before the survey. In this category, capsular glaucoma accounted for 60%, whereas 84% of cases detected during the survey were chronic simple glaucomas. Eight cases (18%) were classified as normal tension glaucoma, all of whom were diagnosed during the survey. Chronic simple glaucoma was significantly more prevalent in males than in females.

Aged↗

Elevated intraocular pressure and pseudoexfoliation of the lens capsule as risk factors for chronic open-angle glaucoma. A population-based five-year follow-up study.

In 1984-86, a glaucoma survey was carried out in a municipality in central Sweden, comprising 760 subjects 65-74 years of age. Since 1988, a follow-up study of those 527 subjects who had normal and reliable visual fields has been in progress. A visual field defect was required for a diagnosis of chronic open-angle glaucoma. By December 1991, 10 cases of capsular glaucoma and 3 cases of chronic simple glaucoma had been found. The standardized relative risk for chronic open-angle glaucoma was 3.4 times (95% confidence interval: 1.1-11) greater in subjects with a baseline intraocular pressure > or = 21 mmHg, using the highest pressure in either eye, than in those with an intraocular pressure < 21 mmHg. Pseudoexfoliation increased the standardized relative risk 9.8-fold (95% confidence interval: 2.5-38). There was indication of effect modification between intraocular pressure and pseudoexfoliation. Optic disc haemorrhages were associated with a 4.8-fold (95% confidence interval: 0.63-37) increased unadjusted risk. The study supports the pressure theory of optic nerve damage in glaucoma. Pseudoexfoliation was recognized as an independent risk factor for the development of chronic open-angle glaucoma.

Aged↗

Chronic open-angle glaucoma and advanced visual field defects in a defined population.

In a case-finding study in a municipality in central Sweden, 128 cases of chronic open-angle glaucoma with visual field defects (VFD) were found. The prevalence amounted to 1.4% in those greater than or equal to 45 years of age. Sixty-three percent had capsular glaucoma. Advanced visual field defects (AVFD), i.e. a restriction of the visual field to a diameter of less than or equal to 20 degrees, were seen in 49 patients. Four patients had AVFD in both eyes. Patients with AVFD were older, had had the disease longer, had higher mean initial intraocular pressure (IOP), and had more extensive VFD at the time of diagnosis. When age and duration were taken into consideration, the risk of developing AVFD was 14 times greater in those with VFD stage III at the time of diagnosis, i.e. a Bjerrum scotoma with nasal breakthrough or more widespread VFD. An IOP of greater than or equal to 35 mmHg signified that the risk of having VFD stage III at the time of diagnosis, when age and type of glaucoma were taken into consideration, was 8.6 times greater than if the IOP was less than 35 mmHg.

Aged↗

Comparison of foscarnet and foscarnet esters as anti-influenza virus agents.

Foscarnet is shown to inhibit influenza A virus replication by inhibiting viral RNA synthesis in infected cells. Viral RNA synthesis by isolated nuclei from infected cells was as sensitive to foscarnet as viral RNA synthesis by enzymes from isolated virions or viral cores. It is, therefore, unlikely that the mere association of the polymerase in a replication complex, as in isolated nuclei and infected cells, is the reason for the fact that foscarnet is 10-20 times less active in inhibiting virus replication than cell-free RNA synthesis. We, therefore, tested 44 esters of foscarnet for improved antiviral effect. Of these only a few phenyl esters were more potent than foscarnet itself. These esters did not inhibit the viral RNA polymerase activity and may be hydrolyzed intracellularly to foscarnet. The increased antiviral potency of the phenyl esters was, however, accompanied by increased cellular toxicity, and these compounds, therefore, were less selective antiviral agents than foscarnet. The results suggest that it is not possible to increase the anti-influenza activity of foscarnet by converting it to an ester.

Antiviral Agents↗

Mineralization in the midpalatal suture after orthodontic expansion.

A new method is described for an objective measurement of the mineralization in the anterior part of the midpalatal suture after its orthodontic expansion. The radioisotope 125I is used as radiation source and is placed intraorally in the same position on each measurement occasion. The extraoral part of the apparatus consisted of a scintillation crystal and a pulse-height analyzer to determine the number of roentgen quanta transmitted. The measurements showed that the mineral content within the suture rose rapidly during the first month after the completion of suture opening. In the bone beside the suture, the mineral content decreased sharply during the first month of measurement; later it returned to the initial level.

Child↗