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Biomedical subjects

H Rasmussen

Publications and source records attributed to H Rasmussen.

At least 253 records · Page 14Linked to original sources
PubMed1978

Synthesis and characterization of 2-nitro-5-aziodobenzoylglycyloxytocin, an oxytocin photoaffinity label.

The oxytocin analogue, 2-nitro-5-azidobenzoylglycyloxytocin (NAB-Gly-oxytocin), has been synthesized and purified. The analogue is a full agonist for the stimulation of osmotic water flow in the toad urinary bladder (one-half maximal activity at 3.2 X 10(-6)M). It also enhances [14C]urea permeability in this tissue. Repetitive photolysis in the presence of NAB-Gly-oxytocin (8 X 10(-6)M) results in a progressive permanent inhibition of oxytocin stimulated urea permeability but does not alter hormone induced 3H2O movement. The inhibition is dependent on the photogeneration of the aryl nitrene intermediate and is relieved by protecting the hormone receptor with excess oxytocin (10(-6)M) during the photolysis. These results suggest that the photodependent permanent inhibition of the response to oxytocin in the toad bladder is due to covalent incorporation of the photoaffinity label, NAB-Gly-oxytocin, into the hormone receptor.

Affinity Labels↗
PubMed1978

Photoaffinity labeling of the antidiuretic hormone receptor.

A study to determine the feasibility of photoaffinity labeling the antidiuretic hormone receptor in the toad urinary bladder has been carried out. Two photoactivated derivatives of oxytocin have been synthesized, purified, and characterized chemically and biologically. Photolysis of the toad bladder in the presence of one of these derivatives, 2-nitro-5-azidobenzoylglycyloxytocin, produces a permanent inhibition of the response to native oxytocin. This inhibition can be relieved by protecting the hormone receptor with excess oxytocin during the photolysis. These results suggest that the photolysis-dependent inhibition of the response to native hormone is due to covalent incorporation of the photoaffinity label into the hormone receptor.

Affinity Labels↗
PubMed1978

The effect of 1alpha(OH)D3 and 1alpha,25(OH)2D3 on the bone in patients with renal osteodystrophy.

Six patients with chronic renal disease and variable degrees of renal osteodystrophy were treated for three weeks with either 1alpha,25-dihydroxyvitamin D3 (1alpha25(OH)D3) or 1alpha,hydroxyvitamin D3 (1alpha(OH)D3) and both the biochemical and osseous responses measured. The most consistent changes seen were an increase in serum calcium concentration to normal, a decrease in immunoreactive parathyroid hormone toward normal, an increase in the extent of the calcification front and a decrease in the extent of fibrous dysplasia in the marrow cavity. Two important parameters which did not change significantly were serum alkaline phosphatase activity and the osteoid volume. These data, in conjunction with that from previous studies, indicate that therapy with 1alpha,25(OH)2D3 or 1alpha(OH)D3 does not heal the osteomalacia of renal osteodystrophy, but that it does suppress the secondary hyperparathyroidism, and ameliorate the osteitis fibrosa seen in patients with chronic renal disease. They raise the likelihood that additional factors, such as metabolites of vitamin D other than 1alpha,25(OH)2D3, play a role in regulating bone formation and/or mineralization.

Aged↗
PubMed1978

The effects cytochalasin B on the surface morphology of the toad urinary bladder epithelium: a scanning electron microscopic study.

Cytochalasin B depresses the hydroosmotic response of the toad urinary bladder to vasopressin without affecting basal (bulk flow) permeability, diffusional permeability, or the hormone induced increase in short circuit current. Fine structural studies demonstrated that this macrolide fungal metabolite, in the presence of both an osmotic gradient and vasopressin, induces the formation of large intracellular vacuoles or 'lakes' in epitelial cells lining the bladder mucosa. Some surface changes (shortening and irregularity of microvilli, clumping of the glycocalyx, etc.) were reported by transmission electron microscopy. Scanning electron microscopy demonstrates that cytochalasin B drastically alters the mucosal surface morphology of the hormone stimulated bladder. Lesser changes were seen in the absence of vasopressin. In the presence of arginine vasopressin, excessive cellular swelling and possible rupturing, as well as surface membrane infolding and rippling, were seen in the cytochalasin treated tissues, The specific entity most affected by this treatment is the granular cell.

Animals↗
PubMed1978

Oxygen-sensitive stages of the cell cycle of human diploid cells.

We had established that growth of human diploid WI-38 cells is reversibly inhibited by elevated partial pressures of oxygen (PO2) and we were interested in determining where in the cell cycle growth was delayed. A technique combining cytospectrophotometry and autoradiography was used to determine cell cycle parameters. Confluent cells that were subcultivated and exposed to a PO2 of 365 +/- 8 mm Hg were delayed primarily after DNA synthesis but before metaphase. At a PO2 of 590 +/- 35 mm Hg, most cells did not initiate DNA synthesis, and the few that did, failed to complete the process. When exponentially growing cells that had already begun DNA synthesis were exposed to a PO2 of 590 p 35 mm Hg, they accumulated after completing DNA synthesis but before initiating mitosis. The rate at which (3H)thymidine was incorporated into DNA was inversely correlated with oxygen tension (PO2 of 135--590 mm Hg). These results suggest that the process most sensitive to oxygen causes cells to be delayed after DNA synthesis but before metaphase. Slightly higher PO2's were needed to inhibit the initiation of DNA synthesis. Further, the rate of DNA synthesis is decreased by elevated oxygen tensions.

Cell Cycle↗
PubMed1978

Dependence of Escherichia coli hyperbaric oxygen toxicity on the lipid acyl chain composition.

This study examines certain membrane-related aspects of oxygen poisoning in Escherichia coli K1060 (fabB fadE lacI) and its parent strain, K-12 Ymel. Cells were grown to exponential or stationary phase in a minimal medium and exposed to air plus 300 lb/in2 of O2 as a suspension in minimal salts. After an initial lag, both strains lost viability with apparent first-order kinetics. Hypebaric oxygen was more toxic to cells harvested during the exponential phase of growth than to cells harvested from the stationary phase of growth for both strains K-12 Ymel and K1060. Control suspensions exposed to air plus 300 lb/in2 of N2 did not lose viability during a 96-h exposure. The sensitivity of the unsaturated fatty acid auxotroph, strain K1060, to hyperbaric oxygen increased as the degree of unsaturation of the fatty acid supplement increased. Cells grown with a cyclopropane fatty acid (9,10=methylenoctadecanoate) were the most resistant; cells grown with a monounsaturated fatty acid (oleate) were intermediate; and those grown with polyunsaturated fatty acids (linoleate and linolenate) were most sensitive to hyperbaric oxygen. The parent strain, K-12 Ymel, lost viability in hyperbaric oxygen most similarly to strain K1060 supplemented with oleate. To determine the relative effect of hyperbaric oxygen on the survival of E. coli with saturated membranes, substrains of K1060 were selected for growth on 12-methyltetrade-canoate or on 9 or 10-monobromostearate. Substrains grown with a saturated fatty acid supplement were equally or more sensitive to hyperbaric oxygen than when the same substrains were grown with a cyclopropane fatty acid supplement. The lipid acyl chain composition was determined in E. coli K1060 before and after exposure to hyperbaric oxygen or hyperbaric nitrogen. The proportion of nonsaturated acyl chain lipid of either the oleate- or the 9,10-methyleneoctade-canoate-supplemented K1060 remained unchanged after hyperbaric gas exposure. In strain K1060 supplemented with linoleate and grown to stationary phase, however, the relative unsaturated acyl chain content after hyperbaric exposure decreased in both gases. This finding prompted an investigation of the role of lipid oxidation in hyperbaric oxygen toxicity. Assays of potential lipid oxidation products were performed with linoleate-grown cells. The lipid hydroperoxide and peroxide content of the lipid extract increased by 6.9 times after 48 h of air plus 300 lb/in2 of O2; malondialdehyde and fluorescent complex lipid oxidation products showed much smaller or no changes. Lipid extracts from hyperbaric oxygen-exposed cells were not toxic to viable E. coli K1060, nor did they increase the rate of loss of viability in cells simultaneously exposed to hyperbaric oxygen. Linoleic acid hydroperoxide at 1.0 mM had no effect on the viability of E. coli K-12 Ymel and only marginally decreased the viability of E. coli K1060 supplemented with linoleate. We conclude that the kinetics of oxygen toxicity in E...

Atmospheric Pressure↗
PubMed1978

Vitamin D metabolites and bone mineralization in man.

A comparison was made of the biochemical and osseous effects of 25-hydroxyvitamin D3 [25(OH)D3], 1 alpha-25-hydroxyvitamin D3 [1 alpha, 25(OH)2D3], and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in adult vitamin D-deficient man. Administration of 50 micrograms/d of 25(OH)D3 for 8 weeks led to a return of the mineralization front to normal associated with a return of TmPO4/GFR to normal, an increase in serum phosphate and calcium concentrations, a fall in serum IPTH, and a rise in serum alkaline phosphatase activity. Giving 2.5 micrograms/d of 1 alpha,25(OH)2D3 did not produce these effects. Administration of 1 alpha, 25 (OH)2D3 caused an increase in intestinal calcium absorption, and a rise in serum calcium associated with a fall in serum immunoreactive parathormone (IPTH) concentrations but no sustained rise in either alkaline phosphatase, serum phosphate concentration, nor in TmPO4/GFR. Its administration caused an increase in the extent of the osteoclastic bone resorption surface but the extent of the mineralization front remained subnormal. Administration of 20 micrograms/d of 24,25(OH)2D3 caused a fall in urinary calcium excretion and in serum IPTH, and a rise in serum alkaline phosphatase, but no change in TmPO4/GFR or serum phosphate, and only a slight increase in the extent of the mineralization front. Combined treatment with 1 alpha, 25(OH)2D3 and 24,25(OH)2D3 led to a return of the mineralization front of normal even though both TmPO4/GFR and serum phosphate concentration remained low. It is concluded that 1alpha,25(OH)2D3 is not the sole biologically active metabolite of vitamin D in man. It is apparent that either 25(OH)D3 or some as yet unidentified metabolite of 25(OH)D3 stimulates the renal tubular reabsorption of calcium and phosphate, and that the subsequent rise in serum phosphate concentrations along with the direct actions of 1 alpha-25(OH)2D3, 24,25(OH)2D3, and possibly 25(OH)D3 on bone cells all participate in the restoration of normal bone formation and bone mineralization in vitamin D-deficient man.

Alkaline Phosphatase↗
PubMed1977

The effect of A23187 upon calcium metabolism in the human lymphocyte.

Treatment of human peripheral lymphocytes with mitogenic concentrations of the divalent cation ionophore A23187 led to an initial marked increase in the uptake of calcium by these cells, but the amount of accumulated calcium retained decreased with time so that after 8-12 h of culture, the calcium content of treated cells was only 1.5-2.0-fold higher than that of control cells. Three possible explanations for the biphasic nature of ionophore-induced calcium uptake were considered: (1) the ionophore underwent chemical or metabolic inactivation upon prolonged incubation; (2) massive accumulation of calcium caused irreversible uncoupling of mitochondria in these cells with consequent loss of accumulated calcium; or (3) with time there was a redistribution of ionophore within the cell, and sufficient ionophore was taken up by internal, most likely mitochondrial, membranes to cause an efflux of calcium from internal stores. By developing a bioassay for ionophore and examining the time-dependent effects of ionophore in the presence and absence of calcium, it was concluded that the third explanation was the most likely. The general implications of these results are discussed.

Anti-Bacterial Agents↗
PubMed1977

Effect of ionophore A23187 upon membrane function and ion movement in human and toad erythrocytes.

Addition of 0.1-0.3 micronM A23187, a divalent cation ionophore, to human erythrocytes suspended in a 1.0 mM 45Ca2+ -containing buffer results in a small (approximately two fold) increase in [Ca2+]i, a significant decrease in osmotic fragility, and a decrease in intracellular K+ (100 mmoles/liter of cells to 70 mmoles/liter cells) without significant alteration of intracellular [Na+]. This decrease in [K+]i is associated with a significant decrease in packed cell volume and correlates directly with the observed alteration is osmotic fragility. Increasing extracellular K+ to 125 mM prevents the A23187-induced changes in osmotic fragility, K+ content and cell volume, but does not prevent the ionophore-induced uptake of 45Ca2+. Addition of 0.1-0.3 micronM A23187 to toad erythrocytes leads to an increase in 45Ca2+ uptake comparable to that observed in human erythrocytes, but does not alter osmotic fragility, cell volume or K+ content. Higher concentrations of ionophore (3.0-10.0 micronM) cause a 30- to 50-fold increase in 45Ca2+ uptake and concomitant change in K+ content, cell volume and osmotic fragility. These changes in cell properties can be prevented by increasing extracellular [K+] to 90 mM. The difference in sensitivity of the two cell types to A23187 is attributed to the presence of additional intracellular calcium pools within toad erythrocytes that prevent an increase in cytoplasmic Ca2+ until Ca2+ uptake is increased substantially at the higher concentrations of A23187.

Adenosine Triphosphate↗
PubMed1977

The mitogenic effect of A23187 in human peripheral lymphocytes.

The mitogenic action of the divalent ionophore A23187 was confirmed and shown to be very sensitive to changes in extracellular calcium ion concentration. At optimal calcium and ionophore concentrations, an increase in [3H]-thymidine incorporation was seen that was similar to that seen after phytohemagglutinin addition. A calcium-dependent stimulation of alpha-aminoisobutyric acid transport was also seen after A23187 addition. Studies with three inhibitors demonstrate a similarity between proliferation induced by phytohemagglutinin and by A23187. Isoproterenol (10(-4) M) and ouabain (10(-7) M) blocked the effects of phytohemagglutinin and A23187. A drug, D-600 that has been shown to block calcium channels in cardiac muscle, inhibited proliferation induced by either phytohemagglutinin or A23187. This concentration of D600 had no effect on either phytohemagglutinin- or A23187-induced 45Ca2+ uptake. Furthermore, the (+) and (-) isomers separated from racemic D600, which have been shown to block sodium and calcium channels respectively in smooth muscle, had equal potency in blocking lymphocyte proliferation.

Aminoisobutyric Acids↗
PubMed1977

Adrenal glucocorticoids, adenine nucleotide translocation, and mitochondrial calcium accumulation.

The administration of dexamethasone to rats markedly diminished the initial rate and maximal extent of substrate-dependent calcium uptake in subsequently isolated liver mitochondria, and enhanced the release of calcium. The apparent Km for calcium transport was not altered by dexamethasone treatment and it ranged from 50 to 80 muM when an EDTA/Ca buffer system was used in the presence of magnesium, and 20 muM when an NTA/Ca buffer system without magnesium was employed. In contrast, when ATP was employed as the energy source, there was no significant difference in initial rate, Km, or the extent of calcium accumulation between mitochondria from control and dexamethasone-treated animals. Although mitochondria from dexamethasone-treated animal showed 15% less cytochrome c oxidase activity/mg of protein, overall respiratory capacity and ATP production from ADP were the same as in control mitochondria. However, mitochondria from dexamethasone-treated animals translocated ATP from inside to outside faster than those from control animals. When the ATP in the medium was depleted by glucose and hexokinase, both types of mitochondria retained essentially all the preloaded calcium until total ATP reached a critical level (7 approximately 5 mumol of ATP/mg of protein). When ATP content fell below this critical level, mitochondria released all the calcium quickly. Dexamethasone treatment increased the susceptibility of mitochondria to the depletion of ATP. These data indicate that the dexamethasone-induced decrease in maximal calcium transport and in calcium retention carrier system per se, but o an altered ability of the mitochondria to regulate intramitochondrial ATP content.

Adenosine Diphosphate↗
PubMed1977

The effect of oxygen and vitamin E on the lifespan of human diploid cells in vitro.

Human diploid cells (WI-38) were serially subcultivated at partial pressures of oxygen (Po2) ranging from 5.6 mm Hg to 608 mm Hg. At a Po2 of 5.6 mm Hg, the number of doublings to phase out was less than that of control cells at a Po2 of 137 mm Hg. Cultures grown at Po2's of 24, 49, or 137 mm Hg grew at the same rate and phased out after a similar number of population doublings. Population lifespan was markedly shortened by chronic exposure to elevated Po2's, a phenomenon that was, in part, reversible. d-1-alpha-Tocopherol (10 microgram/ml or 100 microgram/ml) homogenized into the medium at each weekly subcultivation did not extend the lifespan of cells at reduced, ambient, or elevated oxygen tensions. These results indicate that neither oxygen toxicity nor free radical reactions play a significant role in limiting the lifespan of WI-38 cells grown in vitro under ambient oxygen tensions (Po2 137 mm Hg).

Cell Division↗
PubMed1977

Electrical and adaptive properties of rod photoreceptors in Bufo marinus. II. Effects of cyclic nucleotides and prostaglandins.

Substances known to alter cyclic nucleotide levels in cells were applied to the isolated toad retina and effects on rod electrical and adaptive behavior were studied. The retina was continually superfused in control ringer's or ringer's containing one or a combination of drugs, and rod activity was recorded intracellularly. Superfusion with cGMP, Bu(2)GMP, isobutylmethylxanthine (IBMX; a phosphodiesterase inhibitor), or PGF(2alpha) (a prostaglandin) caused effects in rods that closely match those observed when extracellular Ca(2+) levels were lowered. For example, short exposures (up to 6 min) of the retina to these substances caused depolarization of the membrane potential, increase in response amplitudes, and some changes in waveform; but under dark-adapted or partially light-adapted conditions receptor sensitivity was virtually unaffected. That is, the position of the V-log I curve on the intensity axis was determined by the prevailing light level, not by drug level. These drugs, like lowered extracellular Ca(2+), also decreased the period of receptor saturation after a bright-adapting flash, resulting in an acceleration of the onset of membrane and sensitivity recovery during dark adaptation. Long-term (6-15 min) exposure of a dark-adapted retina to 5 mM IBMX or a combination of IBMX and cGMP caused a loss of response amplitude and a desensitization of the rods that was similar to that observed in rods after a long-term low Ca(2+) (10(-9)M) treatment. Application of high (3.2 mM) Ca(2+) to the retina blocked the effects of applied Bu(2)cGMP. PGE(1) superfusion mimicked the effects of increasing extracellular Ca(2+). The results show that increased cGMP and lowered Ca(2+) produce similar alterations in the electrical activity of rods. These findings suggest that Ca(2+) and cGMP are interrelated messengers. We speculate that low Ca(2+) may lead to increased intracellular cGMP, and/or that applied cGMP, and/or that applied cGMP may lower cytosol Ca(2+), perhaps by stimulating Ca(2+)- ATPase pumps in the outer segment.

Adaptation, Ocular↗