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Biomedical subjects

Y S Park

Publications and source records attributed to Y S Park.

At least 19 recordsLinked to original sources

Interaction of synthetic glycophospholipids with phospholipid bilayer membranes.

A series of glycophospholipids synthesized by coupling mono-, di-, or tri-saccharides to dioleoylphosphatidylethanolamine (DOPE) by reductive amination was used to investigate the interaction of glycophospholipids with phospholipid bilayer membranes. These synthetic glycophospholipids functioned as a stabilizer for the formation of DOPE bilayer vesicles. The minimal mol% of glycophospholipid needed to stabilize the DOPE vesicles were as follows: 8% N-neuraminlactosyl-DOPE (NANL-DOPE), 20% N-maltotriosyl-DOPE (MAT-DOPE), 30% N-lactosyl-DOPE (Lac-DOPE), and 42% N-galactosyl-DOPE (Gal-DOPE). The estimated hydration number of glycophospholipid in reverse micelles was 87, 73, 46, and 14 for NANL-DOPE, MAT-DOPE, Lac-DOPE, and Gal-DOPE, respectively. Thus, the hydration intensity of the glycophospholipid was directly related to the ability to stabilize the DOPE bilayer phase for vesicle formation. Glycophospholipids also reduced the transition temperature from gel to liquid-crystalline phase (Tm) of dipalmitoylphosphatidylcholine (DPPC) bilayers. Interestingly, incorporation of NANL-DOPE induced a decrease of membrane fluidity of DPPC bilayers in the gel phase while other glycophospholipids had no effect. Also, low level of NANL-DOPE but not other glycophospholipids increased the transition temperature (TH) from liquid-crystalline to hexagonal phase of dielaidoylphosphatidylethanolamine bilayers. These results showed that NANL-DOPE with a highly hydratable headgroup which provides a strong stabilization activity for the L alpha phase of phospholipid membranes, may also be involved in specific interactions with neighboring phospholipids via its saccharide moiety.

1,2-Dipalmitoylphosphatidylcholine

Some negatively charged phospholipid derivatives prolong the liposome circulation in vivo.

A series of negatively charged phospholipid derivatives has been synthesized by coupling aliphatic dicarboxylic acids, HOOC(CH2)nCOOH, to dioleoylphosphatidylethanolamine (DOPE). The individual derivatives were incorporated into egg phosphatidylcholine/cholesterol liposomes (2:1, molar ratio) and injected into mice to test its effect on liposome circulation in vivo. The effectiveness of DOPE derivatives was dependent on the hydrocarbon chain length between the terminal carboxyl group and the amide bond. N-Glutaryl DOPE and N-adipyl DOPE were effective in prolonging the circulation time of liposomes. On the other hand, liposome uptake by the liver and spleen was increased by the addition of N-malonyl DOPE or N-succinyl DOPE, while it was not changed by the addition of N-pimelyl DOPE and N-suberyl DOPE. Our observation suggested that not all negatively charged phospholipids enhance liposome uptake by RES, some even reduce the uptake.

Animals

Cryoprotective activity of synthetic glycophospholipids and their interactions with trehalose.

A series of glycophospholipids have been synthesized by conjugating mono-, di- and trisaccharides with dioleoylphosphatidylethanolamine (DOPE) by reductive amination. These synthetic glycophospholipids were incorporated into egg phosphatidylcholine (PC) vesicles and tested for the release of vesicle-entrapped calcein after five cycles of freeze and thaw. N-isomaltotriosyl-DOPE and N-(N-acetylneuramin-lactosyl)-DOPE had approximately equal activity in cryoprotection; whereas N-lactosyl-DOPE and N-galactosyl-DOPE were without effect. However, the cryoprotective effect of trehalose was significantly reduced with the incorporation of N-lactosyl-DOPE and N-galactosyl-DOPE, but not with the trisaccharide-DOPE conjugates. FTIR studies of mixtures of trehalose and glycophospholipid revealed that trehalose forms H-bonding with the phosphodiester group of N-(N-acetylneuramin-lactosyl)-DOPE but not that of N-galactosyl-DOPE. The presence of interaction of trehalose with the trisaccharide-DOPE conjugate and the absence of interaction with the monosaccharide-DOPE conjugate were also demonstrated by the change of the HII phase transition temperature of dielaidoyl phosphatidylethanolamine as measured by the differential scanning calorimetry. The ability of trehalose to restore the membrane order of the rigid dipalmitoyl phosphatidylcholine bilayer perturbed by the presence of glycophospholipids is also correlated with the ability of trehalose to interact with trisaccharide-DOPE conjugate but not with the monosaccharide-DOPE conjugate. These observations have shed some light on the mechanism of the cryoprotective activity of the membrane bound carbohydrates.

Calorimetry, Differential Scanning

Nitrogen tensions in brachial vein blood of Korean ama divers.

Intravascular bubble formation and symptoms of decompression sickness have been reported during repetitive deep breath-hold diving. Therefore we examined the pattern of blood N2 kinetics during and after repetitive breath-hold diving. To study muscle N2 uptake and release, we measured brachial venous N2 partial pressure (PN2) in nine professional Korean breath-hold divers (ama) during a 3-h diving shift at approximately 4 m seawater depth and up to 4 h after diving. PN2 was determined with the manometric Van Slyke method. Diving time and depth were recorded using a backpack computer-assisted dive longer that allowed calculating the surface-to-depth time ratio to derive the effective depth. With the assumption that forearm muscle N2 kinetics follow the general Haldanian principles of compression and decompression, i.e., forearm muscle is a single compartment with a uniform tissue PN2 equal to venous PN2, PN2 data were fitted to monoexponential functions of time. In the early phase of the diving shift, PN2 rapidly increased to 640 Torr (half time = 6 min) and then slowly declined to baseline levels (half time = 36 min) after the work shift. Peak PN2 levels approximated the alveolar PN2 derived from the effective depth. We conclude that forearm muscle N2 kinetics are well described by a Haldanian single-compartment model. Decompression sickness is theoretically possible in the ama; it did not occur because the absolute PN2 remained low due to the shallow working depth of the ama we studied.

Diving

Increase of heat loss by wearing gloves and boots in wet-suited subjects working in cold water.

The effect of wearing protective gloves and boots on thermal exchanges of wet-suited subjects in cold water was evaluated. Four male subjects, clad in 5 mm-thick neoprene wet suits and either with or without neoprene gloves (5 mm-thick) and boots (5 mm-thick) were immersed up to the neck in water at 13 degrees C while resting for 3 h or exercising for 2 h. Rectal temperature, oxygen consumption and local (chest, back, upper arm, thigh, forearm, calf, hand and foot) skin temperatures, skin heat fluxes and thermal insulations were determined during immersion. The rectal temperature was not different between conditions but the skin temperature was significantly higher with gloves and boots, especially at the distal extremities (forearm, calf, hand and foot). Consequently, the core-to-skin temperature gradient was reduced by wearing gloves and boots, but the skin heat loss was markedly increased. Calculated overall body insulation was significantly lowered by wearing gloves and boots. These results indicate that in wet-suited subjects resting or exercising in cold (13 degrees C) water, gloves and boots increase the overall rate of body heat loss. Attenuation of cold-induced vasoconstriction is proposed as the mechanism.

Adult

Human carbonyl and aldose reductases: new catalytic functions in tetrahydrobiopterin biosynthesis.

New catalytic functions of human carbonyl- and aldose reductase in tetrahydrobiopterin biosynthesis are proposed. 6-Pyruvoyl tetrahydropterin, an intermediate in the biosynthesis of tetrahydrobiopterin, was converted to 6-lactoyl tetrahydropterin and 1'-hydroxy-2'-oxopropyl tetrahydropterin by carbonyl reductase under anaerobic condition. 1'-Hydroxy-2'-oxopropyl tetrahydropterin was subsequently metabolized to tetrahydrobiopterin by aldose reductase. Based on these results alternative pathways for the synthesis of tetrahydrobiopterin in patients with genetic defects of sepiapterin reductase are suggested.

Alcohol Oxidoreductases

Gastric infarction.

We have described a patient with an acute condition of the abdomen who had infarction of the stomach and the small intestine due to atheromatous thrombus of celiac and superior mesenteric arteries. We believe this unusual simultaneous occurrence of gastric and small intestinal infarction is coincidental. The outcome of gastric infarction is frequently fatal.

Aged

Transport kinetics of glucose and alanine in renal brush-border membrane vesicles of cadmium-intoxicated rabbits.

Changes in transport kinetics of D-glucose and L-alanine were studied in renal luminal membrane vesicles isolated from cadmium-intoxicated rabbits. Cadmium intoxication was induced by subcutaneous injections of CdCl2 at a dose of 2 mg Cd/kg/day for 2-3 weeks. Brush-border membrane vesicles were prepared from renal outer cortex and outer medulla by Percoll gradient centrifugation. Cadmium intoxication resulted in a marked attenuation of Na(+)-dependent transports of D-glucose and L-alanine in both outer cortical and outer medullary brush-border membrane vesicles, and this was due to reduction in Vmax and not Km. Similar results were obtained in normal vesicles directly exposed to free cadmium. These results suggest that in long-term cadmium-exposed animals free cadmium ions liberated in the proximal tubular cytoplasm may directly impair brush-border membranes thereby reducing capacity of Na(+)-dependent transport systems for glucose and amino acids.

Alanine

Pseudoseptic arthritis: an unusual presentation of neuropathic arthropathy.

A 49 year old black man with scoliosis presented with bilateral shoulder swelling eventually shown to be due to neuropathic arthropathy related to underlying syringomyelia. The synovial fluid was highly inflammatory, but cultures from synovial fluid and synovial tissue were all sterile. Profuse fat droplets were noted and considered as a possible cause of the inflammation. This is an unusual presentation of neuropathic arthropathy in a patient who was also harbouring an adenocarcinoma that was undetected until later.

Arthritis, Infectious

[A study on comparisons of ice bag and heat lamp for the relief of perineal discomfort].

Perineal discomfort from episiotomy continues to be a problem for many postpartum women. The purposes of this study were to compare the effect of ice bag and heat lamp for the relief of perineal discomfort and to identify the sustaining time of each effect. Forty women took ice bag and heat lamp with random assignment of initial therapy. Women rated the degree of perineal discomfort before and after each therapy and at half-hour, tow-hour and four-hour intervals after each therapy. A discomfort scale, 18cm graphic rating scale, was used. The results of the study were as follows: 1. The ice bag group showed significantly lower discomfort score than the heat lamp group at the half-hour and two-hour intervals after therapy. 2. The ice bag group showed significantly lower discomfort score for 4hrs after than before therapy, but the heat lamp group did not show significantly lower discomfort score. 3. Neither the type of episiotomy nor the previous experience of heat therapy influenced on the effect of ice bag relieving the perineal discomfort. Therefore ice bag was significantly more effective in relieving perineal discomfort than heat lamp. Subjective responses of patients who took both therapy were very favorable toward ice bag. I suggested that nurses should provide women with adequate information about the use of ice bag and encourage to apply ice bag instead of heat lamp after episiotomy in order to promote the relief of perineal discomfort and the healing of perineal wound.

Cold Temperature

Inhibition of topoisomerase I by NAD and enhancement of cytotoxicity of MMS by inhibitors of poly(ADP-ribose) polymerase in Saccharomyces cerevisiae.

The activity of DNA topoisomerase I present in the nuclear extract of yeast, Saccharomyces cerevisiae, was inhibited by additions of NAD, the substrate of poly (ADP-ribose) polymerase. This NAD-inhibited topoisomerase activity was restored to the normal level in a dose-dependent manner by adding 3-aminobenzamide (3-AB), an inhibitor of the polymerase. The 3-AB sensitive polymerase enzyme activity, as determined by the rate of incorporation of the radiolabelled NAD in permeabilized cells, increased by treatment of cells with methyl methanesulfonate (MMS) in a dose-dependent manner. While the additions of MMS increased the polymerase activity, it has caused a decrease in cell survival. However, this cell killing activity of MMS was markedly potentiated by adding benzamide, another inhibitor of polymerase. Thus, these results suggest that the mode of modification of nuclear proteins by altering the poly(ADP-ribosylation) in S. cerevisiae resembles with those observed in mammalian cells.

Benzamides

Purification and characterization of 6-pyruvoyl-tetrahydropterin synthase from Drosophila melanogaster.

The enzyme 6-pyruvoyl-tetrahydropterin synthase (PTP synthase), which catalyzes the conversion of 7,8-dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin, has been purified approx. 230-fold to apparent homogeneity from head extracts of Drosophila melanogaster. A partially purified 6-pyruvoyl-tetrahydropterin reductase (PTP reductase) was also prepared and in its presence, along with Mg2+ and NADPH, the purified PTP synthase converted 7,8-dihydroneopterin triphosphate to metastable 6-lactoyltetrahydropterin, which was autoxidized to sepiapterin under aerobic conditions. Purified PTP synthase had a specific activity of 3792 units per mg protein and migrated as a single protein band on both nondenaturing polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purified active enzyme consisted of at least two identical subunits which had a molecular mass of 37.5 kDa on SDS-PAGE and NH2-Asx-Pro- as N-terminal amino acids. The native enzyme in crude extract was shown to be more complex, existing as higher multimeric forms.

Alcohol Oxidoreductases

Tandemly duplicated Caenorhabditis elegans collagen genes differ in their modes of splicing.

Caenorhabditis elegans contains 50 to 150 collagen genes dispersed throughout its genome. We have determined the complete nucleotide sequences of two collagen genes, col-12 and col-13, that are separated by only 1800 bases and are transcribed in the same direction. The 951 nucleotides of their coding regions differ by only five nucleotides (99.5% identity). The amino acid sequences are identical except for two conservative amino acid changes within the putative secretory signal sequences, so the mature forms of the col-12 and col-13 collagens would be identical. The position and sequence of the intron (52 base-pairs) within the coding region of each gene are perfectly conserved. In contrast to the coding regions and the introns, the 5' and 3' flanking regions show little sequence similarity, col-12 and col-13 are expressed at similar levels at the same developmental stages, and appear to utilize conserved TATA boxes and transcription start sites. The major differences between the genes is that, preceding the initiator ATG, col-12 has a cis-spliced intron, while col-13 is transspliced. Thus, col-12 and col-13 are essentially identical in all aspects except that the col-12 mRNA has a 26-nucleotide cis-spliced leader at the same place where the col-13 mRNA has a 22-nucleotide trans-spliced leader. These results suggest that col-12 and col-13 are derived from a gene duplication and that sequence homology in the coding regions, but not in the flanking regions, has been maintained by gene conversion. The fact that the only significant difference between the two genes is in their modes of splicing suggests that cis and trans-splicing can be interchanged during gene evolution.

Amino Acid Sequence

Impact of practice on speed of mental rotation.

We tested 11- and 20-year-olds on 3360 trials of a mental rotation task in which they judged if stimuli presented in different orientations were letters or mirror images of letters. Children's and adults' processing times decreased substantially over practice. These changes were well characterized by hyperbolic and power functions in which most of the parameters of those functions were constrained to adults' values. Performance on two transfer tasks, mental rotation of letter-like characters and memory search for numbers, indicated that the practiced skill did not generalize to other domains. The results are discussed in terms of different mechanisms that might be responsible for the impact of practice.

Adult

Alteration of renal amino acid transport system in cadmium-intoxicated rats.

Effects of cadmium intoxication on renal transport systems for various amino acids were studied. Subcutaneous injections of CdCl2, at a dose of 2 mg Cd/kg.day for 2 weeks, resulted in polyuria, proteinuria, glycosuria, phosphaturia, and aminoaciduria, as observed in chronic cadmium-intoxicated humans and experimental animals. The nature of aminoaciduria was nonspecific, including iminoacid as well as almost all species of neutral, acidic, and basic amino acids. In renal cortical brush border membrane vesicles isolated from cadmium-intoxicated rats, Na(+)-dependent transport of L-proline, L-alanine, and L-lysine was markedly attenuated, whereas the amino acid transport in the basolateral membrane vesicle was not significantly affected. Similar results were obtained in the normal membrane vesicles directly exposed to inorganic cadmium. These results indicate that cadmium intoxication impairs various Na(+)-amino acid cotransport systems in the renal brush border membrane, which leads to panaminoaciduria.

Amino Acids

Transport of organic compounds in renal plasma membrane vesicles of cadmium intoxicated rats.

Effects of cadmium intoxication on renal transport systems for various organic compounds were studied. Subcutaneous injections of CdCl2 (2 mg Cd/kg.day) for two to three weeks induced marked polyuria, glycosuria, and proteinuria without altering glomerular filtration rate. In renal cortical brush border membrane vesicles (BBMV) isolated from cadmium treated rats, Na(+)-dependent D-glucose uptake was markedly attenuated, and this was due to reduction in Vmax and not Km. Likewise, Na(+)-driven L-glutamate transport and H(+)-driven tetraethylammonium transport were significantly reduced. In renal cortical basolateral membrane vesicles (BLMV) of cadmium intoxicated rats, Na(+)-dependent succinate transport was drastically reduced. These results indicate that cadmium intoxication impairs various transport systems for organic compounds in the brush border and basolateral membranes of proximal renal tubules.

Cadmium Poisoning