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H C Andersson

Publications and source records attributed to H C Andersson.

At least 37 records · Page 2Linked to original sources
PubMed1992

No adaptive response of Chinese hamster ovary cells to low doses of ionizing radiation.

Chinese hamster ovary (CHO) cells that had been exposed to very low doses of ionizing radiation from incorporated tritiated thymidine or X-rays were shown not to be more resistant to the induction of chromatid aberrations by a subsequent higher dose of ionizing radiation than previously untreated cells. The adaptive response to ionizing radiation was absent both in cells challenged with high doses of X-rays (1.25 Gy) and in cells post-treated with thermal neutrons (0.5-1 x 10(12) n/cm2). In agreement with these observations in CHO cells we were unable to demonstrate an adaptive response to X-rays also in human lymphocytes from five different donors.

Adaptation, Physiological↗
PubMed1990

Pulsed amperometric detection of carbohydrates in lysosomal storage disease fibroblasts: a new screening technique for carbohydrate storage diseases.

A first step in determining the metabolic defect in patients with an unknown storage disease is to identify the stored material. In the case of fibroblasts storing carbohydrates, this can be accomplished by trifluoroacetic acid (TFA) hydrolysis producing monosaccharides which are separated by anion-exchange chromatography and quantitated by pulsed amperometric detection. This technique separates neutral, amino, and acidic monosaccharides in a single run with a detection limit of 50 pmol. The method, applied to hydrolyzed 100,000 g supernatants of ten normal fibroblast sonicates, revealed a mean +/- S.D. content of the following monosaccharides (in nmol/mg of protein): fucose, 7 +/- 3; galactosamine, 4 +/- 2; glucosamine, 20 +/- 3; galactose, 11 +/- 3; mannose, 27 +/- 6; glucuronic acid, 56 +/- 28; iduronic acid, 17 +/- 11. Six mucopolysaccharidosis fibroblast strains (types I, II, IIIB, IVA, VI and VII) contained 2 to 8 times the normal glucuronic acid levels, and types I and II exhibited 10- to 30-fold normal levels of iduronic acid and 40-fold increases in galactosamine. All the mucopolysaccharidoses could be distinguished from normal based upon an increased concentration of some monosaccharide. Fibroblasts from patients with mannosidosis and fucosidosis contained 7-fold normal amounts of mannose and 11-fold normal amounts of fucose, respectively. The quantitation of monosaccharides in fibroblasts after TFA hydrolysis can identify cells that store excess amounts of a glycosaminoglycan, glycoprotein, oligosaccharide or, presumably, a glycolipid. This may comprise the first step toward identifying novel lysosomal storage disorders and point the way toward new glycoconjugate degradative pathways.

Carbohydrate Metabolism↗
PubMed1990

Swallowing dysfunction in nephropathic cystinosis.

BACKGROUND: Nephropathic cystinosis causes renal failure in most patients at approximately 10 years of age. This can be prevented or retarded by cystine-depleting therapy with oral cysteamine. Many patients who do not receive adequate cysteamine therapy undergo renal transplantation, but the accumulation of cystine continues in other organs, resulting in various clinical abnormalities. We report age-related swallowing dysfunction in patients with nephropathic cystinosis. METHODS: We studied 43 patients with cystinosis (24 who had received a renal transplant and 19 who had not), 3 to 31 years of age. Oral motor function was assessed by a cranial-nerve oral sensorimotor examination, and an oral motor index was calculated for each patient. The oral phase of swallowing was assessed by ultrasonography, and the pharyngeal and esophageal phases were evaluated by videofluoroscopy. RESULTS: Approximately half the patients were slow eaters. Oral motor dysfunction, reflected by a higher oral motor index, increased with age. Speech, oral structure and anatomy, and tongue and lip strength were particularly affected. Seven of nine patients 21 to 31 years old had abnormalities in all three phases of swallowing; the deficits were variable in younger patients. In 28 patients with cystinosis, the mean (+/- SD) duration of oropharyngeal swallowing for a dry swallow (3.06 +/- 1.06 seconds) was longer than in 14 normal subjects (1.89 +/- 0.57 seconds; P less than 0.001). This prolongation reflected impairment of the initiation phase of swallowing. CONCLUSIONS: Swallowing dysfunction is a late complication of nephropathic cystinosis, probably related to muscular dysfunction. Changes in the consistency of foods, swallowing exercises, and long-term cysteamine therapy should be considered for patients with cystinosis who have difficulty in swallowing.

Adolescent↗
PubMed1990

Characterization of lysosomal monoiodotyrosine transport in rat thyroid cells. Evidence for transport by system h.

Lysosomal transport of monoiodotyrosine was characterized in countertransport experiments using rat FRTL-5 thyroid cell lysosomes. Monoiodotyrosine carrier activity was temperature-dependent (Ea = 11.65 kcal/mol) and had a pH optimum of 7.5. Carrier activity was minimally inhibited by KCl and NaCl, but unaffected by the presence of other ions or ATP. Monoiodotyrosine transport was unaffected by the presence of carbonyl cyanide m-chlorophenylhydrazone, nigericin, or ammonium chloride, indicating that a proton or K+ gradient is not necessary for monoiodotyrosine transport across the lysosomal membrane. Monoiodotyrosine countertransport showed a 6-fold increase in lysosomes from FRTL-5 cells grown in medium containing thyrotropin by comparison to cells grown without this hormone. Thyrotropin responsiveness raised the possibility that monoiodotyrosine was transported by system h, the only known lysosomal carrier whose activity is enhanced by thyrotropin. Consistent with this, monoiodotyrosine-loaded lysosomes exhibited countertransport of [3H]tyrosine, [3H]phenylalanine, and [3H]leucine, three system h ligands, but not [3H]cystine, a nonsystem h ligand. Unlabeled tyrosine, phenylalanine, and leucine, but not cystine or proline, inhibited [125I]monoiodotyrosine countertransport, and leucine inhibition of [3H]tyrosine countertransport and [125I]monoiodotyrosine countertransport yielded virtually identical KI values, 3.5 and 3.2 microM, respectively. Competition studies with monoiodotyrosine analogues showed that system h recognizes a broad range of ligands with an alpha-amino acid configuration at one end and a hydrophobic region at the other. Ring-substituted halogens, regardless of mass or ring position, but not amino, nitro, hydroxy, or methoxy groups, enhanced carrier recognition of system h analogues. It appears that a single system effects the transport of iodinated (e.g. monoiodotyrosine) and noniodinated (e.g. tyrosine) thyroglobulin catabolites into the cytosol for salvage and reutilization by FRTL-5 thyroid cells.

Animals↗
PubMed1990

Defective glucuronic acid transport from lysosomes of infantile free sialic acid storage disease fibroblasts.

Separation by h.p.l.c. and pulsed amperometric detection were employed to measure glucuronic acid (GlcUA) and other acidic monosaccharides in fibroblasts from patients with infantile free sialic acid storage disease (ISSD) and Salla disease. These lysosomal storage disorders result from defective carrier-mediated transport of free N-acetylneuraminic acid (NeuAc) out of cellular lysosomes. Three Salla disease fibroblast strains stored approx. 0.4 nmol of free GlcUA/mg of cell protein, whereas four ISSD strains stored approx. 5 nmol GlcUA/mg (normal is undetectable). The GlcUA content of the mutant cell strains, which by differential centrifugation and Percoll gradient fractionation was localized to the lysosomes, averaged 5% of the free NeuAc content of the cells. N-Glycolylneuraminic acid (NeuGc) also accumulated in ISSD cells, but only when they were grown in the presence of fetal calf serum, which contains abundant NeuGc. No other acidic monosaccharides were detected in any of the mutant cell strains. GlcUA egress studies revealed that 56% of the initial GlcUA content was lost from normal granular fractions after 2 min at 37 degrees C. For similarly loaded ISSD granular fractions, virtually no GlcUA was lost even after 6 min. The results indicate that GlcUA is recognized and transported by the lysosomal NeuAc carrier, and that GlcUA transport is impaired in the lysosomal disorders of free NeuAc storage.

Biological Transport↗
PubMed1989

Carrier-mediated transport of monoiodotyrosine out of thyroid cell lysosomes.

Monoiodotyrosine (MIT) crosses the lysosomal membrane of rat FRTL-5 thyroid cells by a carrier-mediated process. In egress studies, MIT lost from inside lysosomes was quantitatively recovered outside lysosomes as MIT, indicating that the compound was transported intact across the lysosomal membrane. In uptake studies, [125I]MIT entry required intact lysosomes and exhibited saturation kinetics. The apparent Km for MIT was approximately 1.5 microM and the Vmax was approximately 0.24 pmol/unit hexosaminidase/min. Countertransport of MIT was demonstrated, with an initial velocity of [125I]MIT uptake which reached a maximum at high intralysosomal MIT loading. Nonradioactive MIT and diiodotyrosine competed to approximately equivalent extents with [125I]MIT for uptake in countertransport experiments. The existence of a lysosomal MIT carrier in thyroid cells may explain how this product of thyroglobulin catabolism is transported to the cytosol for iodine salvage and reutilization.

Animals↗
PubMed1989

The production of chromosomal alterations in human lymphocytes by drugs known to interfere with the activity of DNA topoisomerase II. I. m-AMSA.

The frequencies of chromosomal aberrations and sister chromatid exchanges (SCE) were studied in human peripheral lymphocytes after exposure of whole blood cultures to the antitumour agent m-AMSA. Chromosome-type aberrations were found in cells exposed before stimulation or during the G1-phase of the cell cycle. Chromatid-type aberrations were obtained in cells exposed during the S- and G2-phases, but also in cells exposed the G1-phase or before stimulation. Treatment of lymphocytes with m-AMSA in the G1-phase or before stimulation had the additional effect of strongly increasing the frequency of SCE. When unstimulated lymphocytes were exposed to m-AMSA, the frequencies of SCE and chromatid-type aberrations, but not the frequency of chromosome-type aberrations, could be strongly reduced by holding the cells in F-10 for 2-4 h before stimulation, or by changing the growth medium after stimulation. A 1-h incubation in growth medium was sufficient for obtaining this reduction. The medium in which the m-AMSA-treated cells were incubated for the first 3 h after stimulation proved to be capable of inducing chromatid-type aberrations in late S/G2-phase and SCEs in the S-phase. These observations show that the chromatid-type aberrations and SCEs obtained by exposing unstimulated lymphocytes to m-AMSA were not produced during the treatment itself, but after stimulation at an advanced stage of the cell cycle by an active substance (m-AMSA or a metabolite of m-AMSA) released into the medium during the first hours of incubation. Post-treatments in G2 with 1-beta-D-arabinofuranosylcytosine (ara-C) and hydroxyurea strongly enhanced the frequency of chromatid-type aberrations obtained after treatment of stimulated or unstimulated lymphocytes with m-AMSA. Post-treatments in unstimulated or G1-phase lymphocytes with ara-C did not influence the frequency of chromosome-type aberrations induced by m-AMSA at these stages, but strongly enhanced those induced by X-rays.

Amsacrine↗
PubMed1989

Cystinosis.

Explore the source record for details and available documents.

Adult↗
PubMed1988

Thyrotropin stimulation of lysosomal tyrosine transport in rat FRTL-5 thyroid cells.

Tyrosine countertransport was used to demonstrate the hormonal stimulation of neutral amino acid transport across the lysosomal membrane of FRTL-5 cells. Cells grown with thyrotropin (1 X 10(-10) M) had 7-fold (+/- S.E.) higher tyrosine countertransport activity in their lysosomes than cells grown without thyrotropin. Thyrotropin also stimulated the uptake into tyrosine-loaded lysosomes of other neutral amino acids recognized by the tyrosine carrier, namely, phenylalanine (3-fold) and leucine (6-fold). In contrast lysosomal cystine countertransport was not affected by thyrotropin. Addition of thyrotropin to cells grown without thyrotropin showed that the stimulation of tyrosine counter-transport (a) required at least 48 h to reach the level of the thyrotropin-supplemented cells, (b) depended upon protein synthesis, since cycloheximide (20 microM) was inhibitory, and (c) depended upon RNA synthesis, since actinomycin D (1 nM) was inhibitory. Cells grown without thyrotropin but with dibutyryl cyclic AMP (1 mM) or cholera toxin (1 nM) exhibited enhanced lysosomal countertransport of tyrosine, suggesting that cyclic AMP may act as a messenger. This represents the first demonstration of hormonal responsiveness in a lysosomal transport system and may reflect the importance of salvage and reutilization of lysosomal degradation products for the thyroid epithelial cell.

Animals↗
PubMed1987

Effects of G2 treatments with inhibitors of DNA synthesis and repair on chromosome damage induced by X-rays and chemical clastogens in root tips of Vicia faba. Comparison with corresponding effects in cultured human lymphocytes.

The frequencies of chromatid aberrations produced in roots of Vicia faba by clastogenic (chromosome-damaging) agents were strongly enhanced by exposing the root-tip cells to inhibitors of DNA synthesis during the G2 phase. Chromosome damage produced by both S-dependent (maleic hydrazide, methyl methanesulfonate, thio-TEPA) and S-independent (X-rays, streptonigrin) mechanisms was enhanced by the inhibitor treatments. The types of aberrations affected by the inhibitors were mainly chromatid gaps and breaks and isochromatid breaks of the non-union type. Most effective among the inhibitors tested were hydroxyurea (HU) and 5-fluorodeoxyuridine (FdUrd). Post-treatments with caffeine were effective in enhancing clastogen-induced chromosome damage when given during the S phase. All types of aberrations, exchanges as well as breaks, were enhanced by the post-treatments. When given during the G2 phase, caffeine enhanced only the frequency of chromatid aberrations produced by X-rays. The enhancement was slight and obtained only when the cells were irradiated in the G2 phase and immediately post-treated with caffeine. Clastogen-treated cultures of human lymphocytes responded to post-treatments with inhibitors of DNA synthesis in very much the same way as clastogen-treated root-tip cells of Vicia faba. Thus, the frequencies of chromatid gaps and breaks and isochromatid breaks of the non-union type were strongly enhanced by exposing clastogen-treated lymphocytes to inhibitors of DNA synthesis during the G2 phase. The efficiency of the inhibitors, however, varied considerably in the two materials. On the whole, the number of inhibitors capable of enhancing induced chromosome damage was much larger in lymphocytes than in bean root tips. Only HU was equally effective in both materials. The most striking difference between the two materials was found when caffeine was given as a post-treatment. Thus, in human lymphocytes the frequencies of chromatid aberrations induced by most clastogenic agents were strongly enhanced when caffeine was given during the G2 phase, but little affected by post-treatments with caffeine during the S phase.

Animals↗
PubMed1986

Effect of post-treatments with caffeine during G2 on the frequencies of chromosome-type aberrations produced by X-rays in human lymphocytes during G0 and G1.

Human lymphocytes were irradiated with X-rays in G0 and G1, grown in the presence of 5-bromodeoxyuridine, and harvested at different times from 48 to 80 h after stimulation. Some cultures were exposed to 2.5-5 mM caffeine during the last 3 h before harvesting. The frequencies of chromosome-type aberrations were scored in first division (M1) metaphases. The post-treatment with caffeine increased the frequencies of mitoses and chromosome-type aberrations in irradiated cultures. The results suggest that cells carrying chromosome-type aberrations are delayed in G2 and that caffeine increases the frequencies of aberrations in dividing cells by removing this G2-block.

Caffeine↗
PubMed1985

Sister chromatid exchanges in Tradescantia paludosa.

A modified fluorescence-plus-Giemsa technique is described that allows differential staining of sister chromatids in root tip cells from cuttings of Tradescantia paludosa. With this staining technique, chromatids with both DNA strands unsubstituted are differentiated from chromatids containing 5-bromouracil in place of thymine in one of the strands of the DNA duplex. The baseline level of sister chromatid exchanges was shown to be dependent on the concentration of 5-bromodeoxyuridine in the treatment solution, the mean frequency being 43.5 sister chromatid exchanges per cell for the experimental protocol suggested.

Azure Stains↗
PubMed1984

The effect of G2-treatments with 2'-deoxyadenosine on the frequency of chromatid aberrations in human lymphocytes depends on the type of culture.

The effect of G2-treatments with 2'-deoxyadenosine (dAdo) on the frequency of chromatid aberrations in X-irradiated and unirradiated human lymphocytes depends on the method of culture. In whole-blood cultures dAdo alone produced very few if any aberrations, but in the presence of inhibitors of adenosine deaminase (ADA), such as EHNA or coformycin, a high frequency of chromatid gaps, chromatid breaks, and isochromatid breaks were produced. In cultures of purified lymphocytes, dAdo produced aberrations even in the absence of an ADA inhibitor. Apparently the lymphocytes are protected against the chromosome-damaging effect of dAdo by the ADA activity of the erythrocytes. --When given as a post-treatment, dAdo also enhances the frequency of chromatid aberrations induced by X-rays in G2. In whole-blood cultures this effect is obtained even in the absence of an ADA inhibitor, although the concentration required to produce enhancement is about twenty times higher than in the presence of the inhibitor.

Adenosine Deaminase↗
PubMed1984

High frequencies of chromatid aberrations produced during G2 in human lymphocytes by very low doses (0.025-0.4 Gy) of X-rays in combination with inhibitors of DNA synthesis.

Whole-blood cultures of human lymphocytes were exposed in the G2-phase (3.5 h before harvesting) to various doses of X-rays and post-treated for 3 h with inhibitors of DNA synthesis. The inhibitors used were 2'-deoxyadenosine (dAdo), hydroxyurea (HU) and 1-beta-D-arabinofuranosylcytosine (ara-C). To prevent deamination of dAdo by adenosine deaminase (ADA), the dAdo treatments were carried out in the presence of the ADA inhibitor coformycin. HU and Ara-C were used either alone or in combination. After the 3-h inhibitor treatments, the cultures were harvested and slides prepared and analyzed for chromatid aberrations in metaphase. When the inhibitors were used at concentrations high enough to cause marked chromosome damage by themselves, very low doses of X-rays (0.025-0.2 Gy) were sufficient to produce a dramatic increase in the frequency of chromatid aberrations. High frequencies of chromatid aberrations were also obtained when cultures that had received moderate doses of X-rays (0.4-0.8 Gy) were post-treated with low inhibitor concentrations that produce no or only a few aberrations by themselves.

Chromatids↗
PubMed1980

Chromosomal aberrations and sister-chromatid exchanges in lymphocytes of men occupationally exposed to styrene in a plastic-boat factory.

Workers in a Swedish factory making boats from plastics reinforced with glass fibre are exposed to a variety of chemicals, including styrene which is mutagenic after metabolic activation. The concentration of styrene in the air was measured in the breathing zones of workers occupied with various processes in boat making. Samples of air were taken 6 times during the years 1973-1978. The total exposure to styrene for the workers during this period was calculated and expressed as the average concentration in mg per m3 air during an 8-h workshift multiplied by the number of years of employment. A low-dose group (mean = 137 mg x m-3) and a high-dose group)mean - 1204 mg x m-3) were identified. Blood samples were taken in 1978 from workers belonging to the exposed groups and from a matched control group of employees in the same factory not exposed to styrene. Lymphocytes were cultured and examined for chromosomal aberrations and sister-chromatid exchanges. Exposed workers had a significantly (p less than 0.001) higher number of chromosomal aberrations (36 persons, mean = 7.9 aberrations/100 cells) compared with employees in the control group (37 persons, mean = 3.2 aberrations/100 cells). There was no significant difference between the mean values of the number of chromosomal aberrations between the highly exposed and the less exposed groups. But in the less exposed group there was an increase in the frequency of chromosomal aberrations with increasing exposure to styrene (r = 0.576). In the highly exposed group this dose response was not observed (r = 0.231). For the frequency of sister-chromatid exchanges (SCE) a slight (p less than 0.05) increase was found in the styrene-exposed group (20 persons, mean = 8.4 SCE/cell). The control group (21 persons) had a mean value of 7.5 SCE/cell. Again there was no difference between the highly exposed and the less exposed groups. Other environmental factors that may have clastogenic effects were studied, but multiple regression analysis failed to show a candidate responsible for the increase in chromosomal abnormalities in the exposed group.

Cells, Cultured↗
PubMedDate not supplied

Synergistic enhancement of the frequency of chromatid aberrations in cultured human lymphocytes by combinations of inhibitors of DNA repair.

Whole-blood cultures of human lymphocytes were exposed in the G2-phase to caffeine and to 4 inhibitors of DNA synthesis, hydroxyurea (HU), 2'-deoxyadenosine (dAdo), 1-beta-D-arabinofuranosylcytosine (araC) and aphidicolin (Aph), either individually or in pairs resulting in 10 different possible combinations. Since dAdo is rapidly deaminated in whole-blood cultures, all treatments involving dAdo were carried out in the presence of an inhibitor of the enzyme adenosine deaminase (ADA). The G2-treatments were carried out on 3 different types of culture, (1) cultures that had not previously been exposed to any mutagenic treatment, (2) cultures that had been irradiated with 0.4 Gy of X-rays 3.5 h before harvesting, and (3) cultures that had been exposed for 2 h to 4 X 10(-5) M thiotepa (TT) in G0 immediately before stimulation with phytohaemagglutinin. The aim of the study was to find out in which combinations the inhibitors enhanced synergistically the frequencies of spontaneous and induced chromatid aberrations. In all 3 types of experiment, synergistic effects were observed with most of the 10 combinations, those involving HU being particularly effective. A very strong synergistic enhancement was also obtained when dAdo was combined with Aph.

Aphidicolin↗
PubMedDate not supplied

The effects of post-treatments with caffeine during S and G2 on the frequencies of chromosomal aberrations induced by thiotepa in root tips of Vicia faba and in human lymphocytes in vitro.

The effects of post-treatments with caffeine on the frequencies of chromosomal aberrations induced by the trifunctional alkylating agent thiotepa were studied in human lymphocytes and in root tips of Vicia faba. In lymphocytes the frequency of aberrations induced in G0 or G1 was most strongly increased when the caffeine post-treatments were given during G2. In Vicia faba, on the other hand, the frequency of aberrations induced in early interphase was unaffected by post-treatments with caffeine during G2, but strongly increased when the root tips were exposed to caffeine during the S phase.

Caffeine↗