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Biomedical subjects

M K Song

Publications and source records attributed to M K Song.

At least 55 records · Page 3Linked to original sources
PubMed1989

Zinc, calcium, and magnesium metabolism: effects on plasmacytomas in Balb/c mice.

The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic.

Animals↗
PubMed1989

Healing of necrobiotic ulcers with antiplatelet therapy. Correlation with plasma thromboxane levels.

Necrobiosis lipoidica in diabetics has been considered to be a cutaneous manifestation of diabetic microangiopathy. Seven diabetic patients with necrobiotic ulcers of recent onset that healed after administration of acetylsalicylic acid and dipyridamole had elevated thromboxane levels. Healing was associated with depression of the elevated thromboxane levels in all seven patients.

Adult↗
PubMed1989

Effect of ammoniated barley silage on ruminal fermentation, nitrogen supply to the small intestine, ruminal and whole tract digestion, and milk production of Holstein cows.

The effect of ammonia on barley silage fermentation characteristics, and the digestion and utilization of ammoniated barley silage by lactating Holstein cows fed three isonitrogenous diets (14.5% CP, DM basis) were examined. Whole plant barley was chopped and treated with anhydrous ammonia (1%, DM basis) at ensiling. Untreated barley silage was supplemented with either canola meal or urea. Cows were fed complete mixed diets (50% silage and 50% concentrate mixture, DM basis). Addition of ammonia increased total N, water-insoluble N, lactic acid, and pH in silage. Based on the application rate, 77.7% of the added ammonia N was recovered, and increased water-insoluble N was equal to 49.8% of added ammonia N. Addition of ammonia to barley silage increased ruminal concentrations of ammonia and propionate, and supplies of nonammonia N, microbial N, and total N to the small intestine. Ruminal effective degradabilities of DM and CP of barley silage and complete mixed diets, and whole tract digestibility of DM and CP of complete mixed diets were not affected by supplemental N source. Milk yield and milk composition of cows fed the ammoniated barley silage were similar to those of cows fed the diets supplemented with canola meal or urea.

Ammonia↗
PubMed1988

Transcriptional activation and stabilization of malic enzyme mRNA precursor by thyroid hormone.

One of the responses to the administration of thyroid hormone is an increase in malic enzyme (EC 1.1.1.40) mRNA in rat liver. We have previously shown that 3,5,3'-triiodo-L-thyronine (T3) causes a 3-4-fold increase in the rate of transcription of the malic enzyme gene as determined by in vitro run-off assays with the cDNA probe following T3 treatment for 10 days (Dozin, B., Magnuson, M.A., and Nikodem, V. M. (1986) J. Biol. Chem. 261, 10290-10292). Since the level of cytoplasmic mRNA increases 10-15-fold, one or more additional mechanisms must be operative to produce the full effect. We have now analyzed the time course of the effect of T3 on the rate of transcription and the accumulation of malic enzyme RNA in the nucleus using malic enzyme cDNAs and intronic probes. There is an approximately 10-12-fold increase in the level of nuclear RNA accompanied by the same increase in cytoplasmic mRNA, showing a half-rise time of about 60 h. The 3-4-fold increase in the transcription rate occurred with a half-time of about 18 h. The relative values for either the increase in transcriptional activity or the increase in the level of malic enzyme RNA in the nucleus were identical irrespective of the probes used. As a control, we examined the effect of a high carbohydrate diet which is known to increase malic enzyme mRNA without affecting either transcriptional rate or nuclear RNA (Dozin, B., Rall, J. E., and Nikodem, V. M. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 4705-4709). As expected, no change in the level of malic enzyme RNA in the nucleus was found with the intronic probes. We conclude that T3 both activates transcription of the malic enzyme gene in rat liver and decreases the rate of degradation of pre-mRNA coding for malic enzyme.

Animals↗
PubMed1988

Specific role of manganese and magnesium on RNA synthesis in rabbit bone marrow erythroid cell nuclei.

Specific roles of manganese (Mn) and magnesium (Mg) on the activities of DNA-dependent RNA polymerases I and II isolated from rabbit bone marrow erythroid cell nuclei were investigated. Three main polymerases were separated from the cell nuclei. When RNA polymerase I and Mg were added to the RNA synthesis assay mixture containing erythroid cell DNA as template, RNA transcription activity was highest, but when Mg was replaced with Mn, denatured calf thymus DNA formed a better template than erythroid cell DNA. In contrast, nucleoplasmic DNA from erythroid cell and liver DNA were the best templates to stimulate RNA transcription when RNA polymerase II and Mn were added to the assay mixture. However, if Mn was replaced with Mg, RNA synthesis activity was drastically reduced when the template was nucleoplasmic DNA of erythroid cell. RNA polymerase I and Mg synthesized GC rich RNA, whereas RNA polymerase II and Mn synthesized AU rich RNA. Sedimentation analysis showed that the molecular weights of the RNA produced by polymerase I were larger when the enzyme was activated with Mg than with Mn, whereas those of the RNA produced by polymerase II were larger with Mn than with Mg. Furthermore, RNA produced by polymerase I and Mg using chromatin as a template hybridized better with nucleolar DNA than with nucleoplasmic DNA, whereas that produced by polymerase II and Mn hybridized better with nucleoplasmic DNA than with nucleolar DNA. These results suggest that RNA synthesis is dependent on the activity of specific RNA polymerases and the presence of specific divalent cations and templates, and that the cofactor and template for RNA polymerase I are, respectively, Mg and the nucleolar DNA of cell nuclei, whereas those for RNA polymerase II are Mn and nucleoplasmic DNA.

Animals↗
PubMed1988

Intestinal zinc transport: influence of streptozotocin-induced diabetes, insulin and arachidonic acid.

The influence of arachidonic acid (AA) on the zinc flux rates of jejunal segments, isolated from streptozotocin-induced diabetic rats injected with saline or with insulin, was investigated using an Ussing chamber technique. Although the zinc flux rates from mucosa-to-serosa (Jms) of normal rats were inhibited by addition of 5 microM AA to the jejunal segment bathing medium (46.4 +/- 5.0 vs 32.6 +/- 4.3 nmol/hr/cm2), AA had no effect on the Jms of diabetic rats either with or without insulin treatment. Induction of diabetes also significantly reduced Jms (46.4 +/- 5.0 vs 22.1 +/- 4.9 nmol/hr/cm2), but 3 day insulin treatment (NPH 8 U/Kg/day subcutaneously) did not reverse this effect (29.2 +/- 5.1 nmol/hr/cm2). Addition of AA to the serosal side did not significantly alter the zinc flux rate from serosa-to-mucosa (Jsm) in either control, diabetic or diabetic rats treated with insulin. The net zinc absorption rate (Jnet) of jejunal segments was decreased in diabetic rats compared to controls (13.2 +/- 3.0 vs -0.7 +/- 2.1 nmol/hr/cm2), but normalization of blood glucose with 3 day insulin treatment did not increase Jnet. Addition of AA was associated with a tendency to increase zinc uptake capacity. This change reached statistical significance in insulin treated diabetic rats. Short-circuit current (Isc) for diabetic rats was increased compared to controls but addition of AA to the mucosal side bathing medium decreased Isc in all groups. The results indicate that the zinc flux rate in the small intestine of streptozotocin-induced diabetic rats is decreased, that zinc uptake capacity of the small intestine does not directly reflect the zinc flux rate across the small intestine, and that AA or one of its metabolites may play a significant role in the control of the zinc flux across the intestinal epithelium.

Animals↗
PubMed1988

Characterization of the low mol. wt zinc-binding ligand from rat small intestine by comparison to the organic zinc-binding ligands.

1. 65Zn complexes of picolinate (PA), citrate (CA), L-histidine (L-his), arachidonic acid (AA) or low mol. wt zinc-binding ligand from rat intestine (LMW-ZBL) gave 65Zn eluting peak fraction numbers of 53, 53, 56, 59 and 59 respectively, in a Sephadex G-75 column chromatography. 2. The 65Zn eluting peak fraction numbers with CA, L-his, PA, prostaglandin (PG)E2, AA, no ligand, arachidonate (AT) or LMW-ZBL were 49, 50, 54, 55, 58, 64, 75 and 76 respectively in a Sephadex G-25 column chromatography. 3. In a Sephadex G-15 column chromatography, the 65Zn eluting peak fraction numbers with CA, PGE2, AA, L-his, LMW-ZBL or PA were 49, 50, 51, 52, 52 and 55 respectively. 4. The LMW-ZBL in rat small intestine appears to be an AA-like substance.

Animals↗
PubMed1988

Influence of prostaglandins on unidirectional zinc fluxes across the small intestine of the rat.

1. The regulatory role of prostaglandins (PGs) E2 and F2 alpha on the zinc transport rate across the jejunal segments of rats was examined by employing the Ussing chamber technique. The Zn flux rate from mucosa to serosa across jejunal segments (Jms) was 5.24 (SE 1.54) nmol/h per cm2 (n 48) and that from serosa to mucosa (Jsm) was 15.16 (SE 2.38) nmol/h per cm2 (n 48) when both sides of the segment were bathed with Ringer's bicarbonate solution containing 0.5 mM-zinc chloride and 3 mM-L-histidine. 2. When 5.0 or 50 microM of either PGE2 or PGF2 alpha were added to the serosal side of the tissue, Jsm generally decreased and Jms generally increased, compared with controls. On the other hand, when PGE2 or PGF2 alpha was added to the mucosal side of the tissue, Jms either did not change or increased while Jsm had a tendency to decrease. 3. The Zn uptake capacity of tissue increased significantly when PG was added to the serosal side of the tissue-bathing medium, but not when PG was added to the mucosal side. The uptake capacity of mucosal Zn by jejunal segments was approximately twice that of serosal Zn. 4. When PG was included in the tissue-bathing medium, the short-circuit current, potential difference and conductance between the mucosa- and serosa-bathing media generally decreased. 5. These results suggest that (a) PGs influence Zn flux rate not by chelating Zn and carrying it across the mucosal cell membrane but by interacting with the cytosolic components, (b) it is the serosal PGs which control the Zn flux rate and (c) PGs play a part in triggering a transduction mechanism in the intestinal Zn transport process.

Animals↗
PubMed1987

The intestinal zinc transport in aged rats.

To determine if there are any age-related alterations in the intestinal zinc absorption that may contribute to zinc deficiency, we studied the zinc transport across the jejunal segments of 3-, 12- and 24-month-old Fisher 344 male rats using the Ussing chamber technique. We also evaluated the effect of 5 microM arachidonic acid in tissue bathing media. The zinc transport from mucosa to serosa in 24-month-old rats (55.0 +/- 3.5 nmol/h/cm2) was significantly greater than the transport in 12-month-old (30.1 +/- 6.3 nmol/h/cm2) and 3-month-old rats (41.0 +/- 5.2 nmol/h/cm2). There was no age-dependent differences in the zinc transport from the serosa to the mucosa. The addition of 5 microM arachidonic acid to the serosal side only resulted in a significant decrease in zinc transport rate from serosa to mucosa. The magnitude of change in the 24-month-old rats (36.0 +/- 3.9 vs. 26.5 +/- 3.2 nmol/h/cm2) was similar to the change seen in 12-month-old rats (34.5 +/- 4.6 vs. 20.1 +/- 3.5 nmol/h/cm2) and 3-month-old rats (34.5 +/- 4.6 vs. 26.1 +/- 3.9 nmol/h/cm2). The results indicate that intestinal zinc transport is increased in the aged rats, and that arachidonic acid or one of its metabolites may be important regulators of net zinc absorption through their effect on intestinal zinc secretion rates.

Aging↗
PubMed1987

Low-molecular-weight zinc-binding ligand: a regulatory modulator for intestinal zinc transport.

1. In the last two decades, vast numbers of studies on the zinc nutriture of animals and man have been made. However, the biochemical and physiological events in controlling zinc nutrition are still poorly understood. This report concerns the progress made toward understanding the intestinal zinc absorption and secretion mechanisms. 2. Evidence is accumulating that zinc absorption is a facilitated diffusion while zinc secretion is an active transport. 3. It is known that a low molecular weight zinc-binding ligand (LMW-ZBL) is a key regulator of intestinal zinc absorption, possibly a carrier molecule across the intestinal mucosal cells. Some high molecular weight zinc-binding ligands also appear to be involved in regulating intestinal zinc transport. 4. The identity of the LMW-ZBL is a matter of controversy and its specific role in regulating intestinal zinc transport is not well defined. 5. According to the available literature, no systemic investigations have been made to elucidate the intestinal zinc transport mechanisms, and much more information is needed to fully understand them.

Animals↗
PubMed1987

Influence of dietary zinc content on sodium and potassium metabolism in the rat.

The effect of dietary zinc on the sodium and potassium levels in plasma, soft and peripheral tissues, bone and hair were determined. Sodium levels in plasma, lung and skin of rats fed on a zinc-deficient diet (1.0 microgram/Zn/g) for 4 weeks were significantly lower than those of rats fed on a zinc-sufficient diet (37.5 micrograms Zn/g). Also when rats were fed a zinc-supplemented diet (1 mg Zn/g), sodium levels in hair, femur, muscle and skin were significantly lower than in controls. Interestingly, hair sodium levels were inversely related to the zinc contents in the diets. The potassium levels in fumur, lung, liver, kidney, muscle and skin in zinc-deficient rats and those in hair, femur and skin in zinc-supplemented rats were lower than in controls. In heart they were higher than in controls when rats were fed on either a zinc-deficient or zinc-supplemented diet, but the levels in the kidney increased in relation to the zinc contents in the diets. These results suggest that dietary zinc influences the body sodium and potassium status of animals, that the influence of dietary zinc on organ and peripheral tissues is tissue-specific, that zinc supplementation appears to be beneficial for salt balance of kidney, and that hair sodium content may be a new criterion as to the zinc status of human subjects.

Animals↗
PubMed1986

Relative zinc-binding activities of ligands in the cytosol of rat small intestine.

Relative zinc-binding activities of high-molecular-weight zinc-binding ligand (HMW-ZBL), metallothionein (MT) and low-molecular-weight zinc-binding ligand (LMW-ZBL) in the cytosols of rat small intestines under various experimental conditions were examined. Zinc-binding activities of MT decreased and those of LMW-ZBL increased in the intestinal cytosols from most of the experimental rat groups after incubating at 37 degrees C for 2 hr. The relative zinc-binding activity of MT increased with increasing doses of injected zinc and decreased with orally-administered zinc. Isolated MT did not lose zinc-binding activity during incubation at 37 degrees C for 48 hr, but moved from the MT eluting peak to the LMW-ZBL eluting peak after 1 week.

Animals↗
PubMed1986

Differential effects of transforming growth factor-beta on proliferation of normal and malignant rat liver epithelial cells in culture.

Transforming growth factors (TGF-betas) have been shown to cause both stimulatory and inhibitory effects on cellular growth in a variety of normal and neoplastic cells. The nature of the inhibitory effects of TGF-beta on proliferation of different cell types is at present unclear. We have used freshly isolated rat hepatocytes, a normal diploid rat liver epithelial cell line (NRLM), and a subline (AFB) derived from it which was transformed in vitro by aflatoxin B1 to study the nature of TGF-beta-induced growth inhibition and its alteration following chemically induced neoplastic transformation. TGF-beta had a vastly different effect on proliferation of normal rat liver epithelial cells (both freshly isolated and NRLM cells) compared to aflatoxin B1-transformed cells. TGF-beta at 20 pg/ml caused 83% inhibition of colony formation of NRLM, whereas the growth of AFB cells was unaffected by TGF-beta at concentrations as high as 10 ng/ml. A parallel dose-dependent inhibition of DNA synthesis by TGF-beta was observed in both primary hepatocytes and NRLM cells at concentrations between 10 pg and 10 ng/ml. No inhibition of DNA synthesis was observed in AFB cells. Furthermore, TGF-beta did neither induce anchorage-independent growth of NRLM cells nor affect the growth of AFB cells in soft agar. TGF-beta-induced inhibition of the NRLM cells was irreversible in nature, since treated cells were unable to proliferate and form colonies upon removal of TGF-beta from the medium. Also, NRLM cells showed, after 4 days in the presence of 20 pg of TGF-beta per ml morphological changes characterized by cytoplasmic hypertrophy and the formation of abundant liposomal derivatives, some of which resemble lipofuscin. The finding that TGF-beta caused a high degree of irreversible inhibition of NRLM cells emphasizes the need for caution in interpreting data from inhibition studies, since most assays presently used are designed for assessing growth stimulation in vitro and do not adequately distinguish between the possible cytotoxic and/or cytostatic action of growth inhibitors.

Aflatoxin B1↗
PubMed1985

ADP-ribosylation of metaphase and interphase nonhistones using [3H]adenosine as a radioactive label.

ADP-ribosylation of HeLa nonhistone proteins was investigated by using [3H]adenosine as an in vivo radioactive label. The aim was to determine basic differences in the patterns of modification of interphase and metaphase nonhistones. Fluorography revealed a relatively small number of modified proteins for isolated metaphase chromosomes. In addition to the core histones, a protein of 116 kDa, which is identified as poly-(ADP-ribose) polymerase, was a primary acceptor of [3H]adenosine. Two-dimensional gels revealed a profound difference in the modification of metaphase and interphase nonhistones. For interphase nuclei, 3H label was distributed among a large number of nonhistone acceptors.

Adenosine↗
PubMed1985

Variations in ADP-ribosylation of nuclear scaffold proteins during the HeLa cell cycle.

Cell cycle variations in ADP-ribosylation of nuclear scaffold proteins were determined. Nuclei of synchronized cells were isolated and labeled with [32P]NAD before nuclear scaffolds were obtained by digestion of DNA with DNase I and extraction of proteins with 2M NaCl. Autoradiograms revealed the three groups of "lamins" and a species identified as poly (ADP-ribose) polymerase to be the primary ADP-ribosylated proteins. The patterns of modification of nuclear scaffold proteins displayed similar features through the cell cycle. Radioactivity in the lamins increased from 20% in early-S phase to 40% in G1 phase of the next cell cycle.

Adenine Nucleotides↗
PubMed1985

Decrease in ADP-ribosylation of HeLa non-histone proteins from interphase to metaphase.

Variations for non-histones in the ADP-ribosylating activities of interphase and metaphase cells were investigated. 32P-Labeled nicotinamide adenine dinucleotide ([32P]NAD), the specific precursor for the modification, was used to radioactively label proteins. Permeabilized interphase and mitotic cells, as well as isolated nuclei and chromosomes, were incubated with the label. One-dimensional and two-dimensional gels of the proteins of total nuclei and chromatin labeled with [32P]NAD showed more than 100 modified species. Changing the labeling conditions resulted in generally similar patterns of modified proteins, though the overall levels of incorporation and the distributions of label among species were significantly affected. A less complex pattern was found for nuclear scaffolds. The major ADP-ribosylated proteins included the lamins and poly(ADP-ribose) polymerase. Inhibitors of ADP-ribosylation were effective in preventing the incorporation of label by most non-histones. Snake venom phosphodiesterase readily removed protein-bound 32P radioactivity. A fundamentally different distribution of label from that of interphase nuclei and chromatin was found for metaphase chromosome non-histones. Instead of 100 or more species, the only major acceptor of label was poly(ADP-ribose) polymerase. This profound change during mitosis may indicate a structural role for ADP-ribosylation of non-histone proteins.

Adenosine Diphosphate Ribose↗
PubMed1985

Rapid determination of DNA synthesis in adherent cells grown in microtiter plates.

A specific, rapid, and economical method for measuring the extent of DNA synthesis in adherent rat hepatoma H4-II-E cells grown in 96-well microtiter plates is described. The adherent cells were pulsed for 1 h with [methyl-3H]thymidine, released from the substratum by trypsinization, and collected on fiberglass filters with a MASH II cell harvester. The amount of radioactivity incorporated was directly proportional to the number of cells per well. Growth curves generated by measuring [methyl-3H]thymidine incorporation and counting the number of cells per well were identical. Experiments with inhibitors of DNA, protein, and RNA synthesis demonstrated that this method selectively measured DNA synthesis. In addition, [3H]thymidine uptake showed excellent correlation with autoradiographic assessment of DNA synthesis. This specific and sensitive method for determining DNA synthesis in microtiter cultures should facilitate studies of effects of various growth-controlling agents on epithelial, fibroblastic, and other cells which grow as adherent cells in culture.

Animals↗