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Biomedical subjects

C Hansen

Publications and source records attributed to C Hansen.

At least 127 records · Page 7Linked to original sources
PubMed1993

Retrobulbar adipocytes and humoral immunity in Graves' ophthalmopathy.

As CT and MR-imaging revealed an enlargement of retrobulbar fat tissue in patients with Graves' ophthalmopathy, the role of the retrobulbar adipocytes in the pathogenesis of this disorder remains to be elucidated. To evaluate the in vitro influence of humoral immunity on retrobulbar adipose tissue, the effects of IgG and sera from 56 euthyroid ophthalmopathy patients and 53 controls on both porcine and human (patients' and controls') retrobulbar adipocytes were measured by means of several assays: An enzyme-linked immunosorbent assay was employed to reveal specific binding of antibodies to the adipocytes. Metabolic activity was determined by means of a colorimetric dimethyl thiazolium-diphenyl-tetrazolium bromide test which quantifies the activity of mitochondrial dehydrogenases; cell proliferation was measured by incorporation of [3H]-thymidine in 24 h, and activities of adipocyte specific enzymes, such as membrane-bound lipoprotein lipase and 1-glycerol-3-phosphate-dehydrogenase were determined. By means of these specific enzyme tests no distinctions could be made between patients and controls. Furthermore, a significant difference between patients' (untreated and treated) and controls' IgG to bind to, to activate or to stimulate the proliferation of porcine or human (patients' and controls') retrobulbar adipocytes could not be detected under the employed experimental conditions. The effects of patients' heat-inactivated and non-inactivated sera were indistinguishable from those of the controls. Incubation with autologous sera, however, led to an activation of the retrobulbar adipocytes which was higher than the median caused by the patients' group and that engendered by incubation with autologous IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗
PubMed1993

Response to a single oral test of molybdenum stable isotopes for absorption studies in humans.

Two volunteer subjects were given orally enriched solutions of Mo-95 and Mo-96 respectively. Blood samples were drawn at various times following the tracer administration. The Mo-95 and Mo-96 content in plasma samples was determined by proton nuclear activation and the response to the single oral test of enriched stable molybdenum isotopes was determined. Assuming a simple two-open-compartment model where the first compartment is the gastrointestinal tract and the other is the plasma, an indicative value of the fractional intestinal absorption for the two subjects is given. The feasibility of direct quantitative measurements of Mo intestinal absorption by the double-tracer technique, using stable tracers, is evidenced.

Administration, Oral↗
PubMed1993

Wine for type 2 diabetic patients?

To ensure an acceptable quality of life for Type 2 diabetic patients, the food recommendations have to be as liberal and individualized as possible. Unfortunately, disagreements exists about the consumption of different types of wine. Diabetic patients are advised by some to restrain their wine intake and to use dry wine containing little carbohydrate, while others are more liberal. The purpose of this study was to evaluate the effects of dry and sweet wine on the glycaemic control in Type 2 diabetes. Twelve diabetic patients consumed a light meal with either 300 ml tap water 300 ml dry white wine, 300 ml sweet white wine with ethanol added or 300 ml dry white wine with glucose added. Similar glucose, insulin, and triglyceride responses were obtained in all four situations. There was a greater suppression of the free fatty acid levels in the three situations with wine as compared with water (p < 0.001). This effect may be caused by an attenuation of the free fatty acid mobilization and esterification of free fatty acids to triglycerides induced by alcohol. Our results indicate that patients with well-controlled Type 2 diabetes can drink moderate amounts of wine with meals without risking acute deterioration of glycaemic control. Whether the wine is dry or sweet has no impact on the glycaemic control.

Adult↗
PubMed1993

Effects of exercise or temporary coronary occlusion during angioplasty on right ventricular function with consideration of left-anterior-descending- and right-coronary-artery-related myocardial ischemia.

Whether exercise causes right ventricular ischemia severe enough to depress right ventricular function is still controversial. Therefore, right ventricular function was evaluated in 44 patients with isolated coronary artery disease of either the proximal left anterior descending or right coronary artery during exercise (n = 22) or balloon occlusion during percutaneous transluminal coronary angioplasty (PTCA) (n = 22). Central hemodynamics and right ventricular volumes were determined using a new thermodilution Swan-Ganz catheter. Exercise increased right ventricular end-diastolic volume index [from 89 (66-127) to 101 (70-130) ml m-2, p = 0.00005; median (range)] and stroke volume index [from 44 (27-68) to 53 (36-75) ml m-2, p = 0.0005]. During PTCA, right ventricular end-diastolic volume index remained unchanged, while stroke volume index decreased from 49 (38-60) to 40 (26-49) ml m-2 (p = 0.00005). The decrease in right ventricular ejection fraction during exercise from 56 (41-64) to 52% (39-64) reached only borderline significance (p = 0.06) and was significantly (p = 0.02) smaller than during angioplasty [from 53 (44-62) to 41% (25-66; p = 0.0008)]. Right ventricular ejection fraction did not differ between left anterior descending or right coronary artery obstruction and did not depend on right ventricular afterload. In comparison to exercise angioplasty caused a decreased systolic pressure-volume ratio and a leftward shift of the diastolic pressure-volume curve. In conclusion, exercise has only little effect on right ventricular ejection fraction, whereas inadequate oxygen supply during balloon angioplasty induces severe depression of right ventricular function.

Adult↗
PubMed1993

Detection of carcinogen-DNA adducts in human fetal tissues by the 32P-postlabeling procedure.

Tobacco smoke contains a number of genotoxic compounds that are metabolized to their biologically active forms that subsequently react with cellular DNA to form covalently bound carcinogen-DNA adducts. Several analytical procedures have been developed to detect these adducts in human tissues. Using the nuclease P1-enhanced 32P-postlabeling procedure for bulky adducts, we have detected at least 24 adducts in DNA isolated from placenta and umbilical cord DNA. Adducts were detected in both smokers and nonsmokers, but the relative adduct level (RAL) was significantly higher in smokers (42.8, 8 cases) than in nonsmokers (19.7, 11 cases). The origin of the adducts in nonsmokers remains unknown. The adduct levels in artery DNA were significantly lower than in the vein and the placenta, and a paired nonparametric analysis showed a significant association between the adduct levels in the three tissues. Our results show a maternal transfer of carcinogens present in cigarette smoke to fetal tissues and show that the tissues can metabolize the carcinogens to their DNA binding metabolites. The presence of adducts in fetal tissues may be indicative of genomic damage and may predispose the individual for the development of a serious disease later in life.

Carcinogens, Environmental↗
PubMed1993

Acute effects of graded alcohol intake on glucose, insulin and free fatty acid levels in non-insulin-dependent diabetic subjects.

Alcohol-induced hypoglycaemia is a well-known phenomenon in insulin-treated diabetic subjects. Less attention has been paid to the impact of alcohol on blood glucose and insulin responses in non-insulin dependent diabetic subjects. The aim of this study was to investigate the acute metabolic effects of different alcohol contents added to a non-alcohol beer in 10 non-insulin-dependent diabetes mellitus (NIDDM) subjects. The patients received 500 ml non-alcohol beer with an alcohol percentage (v/v) of 0 (A), 2.7 (B), and 5.4 (C), implying identical contents of ingredients except for alcohol. Blood glucose (mean +/- SE) responses were similar in the three situations (395 +/- 59, 365 +/- 86 and 261 +/- 26 mmol/l x 240 min). In contrast, the incremental insulin response areas increased dose dependently to alcohol (5430 +/- 1158, 9336 +/- 2172 and 12336 +/- 2922 pmol/l x 240 min) and showed a linear correlation (r = 0.39; P < 0.03). The average suppression of serum free fatty acid was similar in the three situations (72.4 +/- 4.4%, 76.3 +/- 6.0% and 68.2 +/- 6.3%). In conclusion, intake of small amounts of alcohol does not acutely deteriorate the glycaemic control in NIDDM. The fact that alcohol results in a dose-related elevation in insulin levels with unaltered blood glucose and free fatty acid responses in NIDDM points to an aggravation of insulin resistance.

Aged↗
PubMed1992

Possible salt bridges between transmembrane alpha-helices of the lactose carrier of Escherichia coli.

Although it is energetically extremely unfavorable to have charged amino acid residues of a polypeptide in the hydrophobic environment of the membrane phospholipid bilayer, a few such charged residues are found in membrane-spanning regions of membrane proteins. Ion pairs (salt bridges) would be much more stable in low dielectric media than single ionized residues. This paper provides indirect evidence for a salt bridge between Asp-240 and Lys-319 in the lactose carrier of Escherichia coli. When Asp-240 was changed to alanine by site-directed mutagenesis, there was a loss of the ability to accumulate methyl-beta-D-thiogalactopyranoside (TMG), melibiose, or lactose. Fast-growing revertants were isolated on melibiose minimal agar plates. Two second-site revertants were isolated: Asp-240-->Ala plus Gly-268-->Val and Asp-240-->Ala plus Lys-319-->Gln. These revertants showed extremely poor accumulation of TMG, melibiose, and lactose, but showed significant "downhill" lactose entry into beta-galactosidase-containing cells with sugar concentrations of 2 and 5 mM. It is concluded that there is some important interaction between Asp-240 and Lys-319, possibly a salt bridge.

Amino Acid Sequence↗
PubMed1992

Stealth liposomes: an improved sustained release system for 1-beta-D-arabinofuranosylcytosine.

Newly developed liposomes with prolonged circulation half-lives and dose-independent pharmacokinetics (Stealth liposomes) have been tested for their efficacy as a slow release system for the rapidly degraded, schedule-dependent, antineoplastic drug 1-beta-D-arabinofuranosylcytosine (ara-C) in the treatment of murine L1210/C2 leukemia. Mice were given injections of either 10(5) cells or 10(6) cells by either the i.v. or the i.p. routes. Leukemia-bearing mice were treated with either i.v. or i.p. injections of free drug, i.v. or i.p. injections of liposome-entrapped drug, or 24-h i.v. infusions of free drug. Long-circulating liposomes contained, as the stealth component, either monosialoganglioside or polyethylene glycol-distearoylphosphatidylethanolamine. Liposomes lacking the stealth components (non-stealth liposomes) were also injected for comparison. At lower dose ranges, stealth liposomes were superior to non-stealth liposomes in prolonging mean survival times of the mice, and all liposome preparations were superior to injections of the free drug. Drug entrapped in stealth liposomes, when administered at or near the maximum tolerated dose of 100 mg/kg ara-C were considerably superior to 24-h free drug infusions given at the same total drug dose. Therapeutic effect was related to the half-life of leakage of ara-C from the liposome formulations, as well as to circulation half-life, with maximum therapeutic effect achieved with long circulation half-lives and more rapid leakage rates. The therapeutic efficacy of non-stealth liposomes increased with increasing liposome (and drug) dose as a result of saturation of liposome uptake by the mononuclear phagocyte system, which resulted in longer circulation half-lives for these liposomes at higher doses (Michaelis-Menten pharmacokinetics). Liposome entrapment can protect rapidly degraded drugs from breakdown in vivo, with release of the drugs in a therapeutically active form over periods of up to several days. The dose-independent pharmacokinetics and reduced mononuclear phagocyte system uptake of stealth liposomes gives them distinct advantages over non-stealth liposomes.

Animals↗
PubMed1992

Transplacental exposure to tobacco smoke in human-adduct formation in placenta and umbilical cord blood vessels.

Smokers are exposed to a large number of genotoxic compounds that react with DNA to form covalently bound carcinogen-DNA adducts after metabolic conversion to their biological active form. Using the P32-postlabeling techniques, tobacco smoke related carcinogen--DNA adducts have been demonstrated in DNA isolated from human placenta and umbilical cord vein and artery obtained from 11 nonsmoking and 8 smoking normal healthy women and foetuses. The adduct level was significantly higher in tissues from smokers than from nonsmokers (P = 0.021), when all tissues were combined. Furthermore, the total adduct level was higher in maternal tissue than the level in fetal tissues (P = 0.030). The adduct level in umbilical cord vein DNA was significantly lower than in placenta, and marginally lower than in umbilical cord artery from the same donor. This suggests that the foetus can metabolise some of the genotoxic compounds found in tobacco smoke to DNA-binding metabolites. The presence of DNA adducts in foetal tissues is indicative of potential genomic damage, that may result in an increased risk for the development of serious diseases, like cancer in childhood or later during the life span of the individual.

Blood Vessels↗
PubMed1992

Effects of interleukin-1, tumor necrosis factor -beta, and forskolin on tissue plasminogen activator activity in human osteoblastic osteosarcoma cells.

The effects of interleukin-1 (IL-1), forskolin, and tumor necrosis factor beta (TNF-beta) on tissue plasminogen activator (t-PA) activity were studied in the human osteoblastic osteosarcoma cell line, G292. t-PA activity was measured in the cell media using the chromogenic substrate, S-2251. After a 24 hour incubation period, IL-1 increased t-PA in a dose-dependent manner. The effect of IL-1 at 10.0 U/ml was partially inhibited in the presence of indomethacin. Forskolin (1.0 microM) increased t-PA activity after 24 hours with the effects of combined treatment of IL-1 (1.0 U/ml, 10.0 U/ml) and forskolin being apparently additive in nature. TNF-beta (10(-8)-10(-7)M) also produced increased t-PA activity in the cell media after a 24 hour incubation period. These results suggest that the cytokines, IL-1 and TNF-beta, can increase t-PA activity in G292 cells and that there is both a cAMP-dependent as well as a cAMP-independent pathway involved in the regulation of this osteoblastic cell function.

Colforsin↗
PubMed1992

Detection of tobacco smoke carcinogen-DNA adducts in cultured rat buccal mucosa cells following exposure to ethanol and total cigarette smoke condensate or chewing tobacco.

Formation of carcinogen-DNA adducts in rat oral epithelial cells after treatment with cigarette smoke condensate (CSC) or chewing tobacco in the presence of ethanol was investigated using the 32P-postlabeling procedure. Concomitant treatment of the cells with ethanol increased the relative adduct level over that found in cells treated with tobacco smoke condensate only. Treatment with chewing tobacco resulted in slightly higher adduct levels than in controls. Treatment of the cells with ethanol did not significantly increase the uptake of a polycyclic aromatic hydrocarbon, benzo[j]fluoranthene, however, high tar CSC alone or in combination with ethanol significantly increased the uptake of radiolabeled benzo[j]fluoranthene, suggesting that increased uptake of the carcinogens may be one of the synergistic mechanisms of alcohol in oral carcinogenesis.

Animals↗
PubMed1992

Decreased performance in a delayed alternation task by rats genetically deficient in vasopressin.

Acquisition and retention of a delayed alternation task by rats genetically deficient in vasopressin (AVP) due to the homozygous occurrence of the Brattleboro diabetes insipidus (DI) gene (M520/DI) were compared to the response of rats that were heterozygous (M520/HZ) or normal (M520/N) with respect to the DI gene. No significant difference in the adaptation to the apparatus was observed between the groups. However, the rate at which the M520/DI rats acquired the alternation task was significantly slower than the acquisition rates of M520/HZ and M520/N rats. In addition, the maximum intertrial interval reached by the M520/DI rats was significantly shorter than the intertrial intervals reached by the M520/HZ and M520/N rats, indicating the ability to retain information was impaired in the M520/DI rats. These results are consistent with the hypothesis that AVP modulates the acquisition and retention of information for normal memory processes.

Animals↗
PubMed1992

Measurement of iron bioavailability by means of stable 54Fe and mass spectrometry.

Stable isotopes represent a useful tool for the assessment of biokinetic parameters in in vivo studies on humans. A procedure is described to evaluate the bioavailability of iron in pharmaceutical preparations by means of 54Fe as a tracer and mass spectrometry for the determination of time dependent changes in the isotope ratio of 54Fe/56Fe in red blood cells. Iron tablets with an increased portion of 54Fe were administered to iron deficient subjects and red cell iron utilization was used as a measure of iron bioavailability. Iron utilization was derived from changes in the 54Fe/56Fe ratio as evaluated by means of fast atom bombardment-mass spectrometry (FAB-MS) on processed blood samples. A good intraindividual reproducibility was observed for blood samples drawn at various times after application of the trial drug. Figures for bioavailability and its interindividual variations were in the range expected from comparable studies on similar iron preparations using radioiron as tracers. The results obtained show that quantitative data of bioavailability from pharmaceutical iron preparations may be obtained without radiation exposure of the subjects investigated.

Administration, Oral↗
PubMed1992

Ultraviolet A irradiation stimulates collagenase production in cultured human fibroblasts.

This study was designed to investigate the biochemical mechanisms responsible for the connective tissue changes seen in actinically damaged skin, which is characterized histologically by diminution and ultrastructural alterations of collagen fibrils and deposition of elastotic material in the papillary dermis. We hypothesized that ultraviolet light could stimulate synthesis of interstitial collagenase in the skin, resulting in collagen degradation. Monolayer cultures of human fibroblasts or keratinocytes were irradiated with ultraviolet A (UVA) or ultraviolet B (UVB) radiation and interstitial collagenase or its inhibitor, TIMP (tissue inhibitor of metalloproteinases) assessed in the conditioned medium with Western immunoblots 24 h after irradiation. Northern blot analysis of the irradiated fibroblasts with a cDNA probe representing collagenase was also performed. Cell viability was greater than 90% with all doses of UV radiation studied. A dose-related increase in immunoreactive collagenase was detected in the medium of fibroblasts irradiated with 0-10 J/cm2 of UVA radiation as well as a parallel increase in the collagenase mRNA in the irradiated cells. UVA radiation stimulated collagenase synthesis in both neonatal and adult fibroblasts. TIMP production in UVA-irradiated fibroblasts increased to a lesser degree than did collagenase and its increase did not parallel the increase in collagenase. UVB (0-100 mJ/cm2) did not stimulate collagenase production by fibroblasts. In contrast to the stimulation of collagenase production by fibroblasts, a slight decrease in immunoreactive collagenase was seen in UVA-irradiated keratinocytes. These data suggest that direct stimulation of collagenase synthesis by human skin fibroblasts by UVA radiation may contribute to the connective tissue damage induced by ultraviolet radiation leading to photoaging.

Cells, Cultured↗