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Biomedical subjects

J Park

Publications and source records attributed to J Park.

At least 361 records · Page 20Linked to original sources
PubMed1993

Abdominal staging of thoracic Hodgkin disease: CT-lymphangiography-Ga-67 scanning correlation.

A retrospective study was performed to assess whether lymphangiography and gallium-67 scanning were complementary to computed tomography (CT) in abdominal staging of disease in 94 patients with early-stage thoracic Hodgkin disease. In 51 patients with surgical or follow-up correlation, the spleen was involved in 16% (n = 8), the spleen and lymph nodes in 22% (n = 11), and only lymph nodes in 2% (n = 1). In these 51 patients, none of the imaging modalities had greater than 50% sensitivity for the detection of nodal involvement. The overall accuracy was similar (71%-82%) for each modality. Analysis of subgroups of patients with lymph nodes measuring less than 10 mm, 10-19 mm, or 20 mm or greater at CT revealed that lymphangiography and gallium scanning added little to the positive or negative predictive values of CT. The sensitivity of CT for detection of splenic disease was 11% (two of 19). On the basis of surgical or follow-up correlation in 51 patients, the authors conclude that lymphangiography and gallium scanning offer minimal or no complementary benefit.

Abdominal Neoplasms↗
PubMed1993

Distinct receptors for cholecystokinin and gastrin on canine fundic D-cells.

Despite the extensive amino acid homology between gastrin and cholecystokinin (CCK) at the biologically active carboxyl terminus, the receptors through which these peptides exert their action are heterogeneous. In previous studies, we have examined the biological activity of gastrin/CCK peptides on isolated canine fundic D-cells and observed that CCK is a more potent and efficacious stimulant of somatostatin release than gastrin. We performed the present studies to distinguish between distinct CCK (CCK-A subtype) and gastrin (CCK-B/gastrin subtype) receptors on canine D-cells. Consistent with this observation was our finding that the CCK-A receptor selective antagonist L-364,718 dose dependently (10(-11)-10(-7) M) inhibited CCK-mediated somatostatin release but at the same doses did not alter the effect of gastrin. CCK and gastrin exhibited similar potency in displacing bound 125I-labeled Leu15 gastrin-17 from D-cells. However, when 125I-CCK octapeptide (CCK-8) was used as the radioligand, a fraction of the bound label could not be displaced with gastrin, but this fraction was completely displaced with CCK-8. In D-cells pretreated with high concentrations of gastrin, L-364,718 was able to inhibit the gastrin-resistant fraction of 125I-CCK-8 binding, but the CCK-B/gastrin receptor selective antagonist (PD 134308) was unable to influence this fraction of binding in doses as high as 10(-6) M. These studies delineate the presence of distinct CCK-A and CCK-B/gastrin receptors on canine fundic D-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Gallop kinematics of Olympic three-day event horses.

Limb contact variables of the gallop of 3-day event horses were determined for competitors in the 1988 Seoul Summer Olympic Games. Horses were filmed during the steeplechase, phase B of the speed and endurance test on day 2 of competition. Two 16-mm high-speed cameras were aimed perpendicularly to the direction of subject motion along a straightaway on the steeplechase track, filmed at 200 frames/s. Thirty-four of 48 competitors were filmed and 108 gallop strides analyzed. Velocity (VEL) averaged 12.09 +/- 0.10 m/s (mean +/- SE), stride length (SL) 6.04 +/- 0.05 m and stride frequency (SF) 2.00 +/- 0.01/s. Superior overall 3-day event performances were associated with faster VEL and longer SL in the steeplechase phase. A linear and quadratic regression of SL and SF against total 3-day penalty points yielded a response surface revealing that the score was optimized with gallop SF between 1.85 and 2.05/s and VEL between 13 and 14.3 m/s. Up to 7 m, there appeared to be no upper limit for optimal SL. This study provided objective documentation of gallop stride kinematic patterns associated with successful performance in world-class 3-day event competition.

Animals↗
PubMed1993

c-Yes tyrosine kinase activity in human colon carcinoma.

To examine the role of Src-related proteins in human colon carcinoma we measured the tyrosine kinase activity of pp60c-src (Src), p62c-yes (Yes), p56lck (Lck), p59fyn (Fyn), p59hck (Hck), p56lyn (Lyn) and p55c-fgr (Fgr) from colonic cells. Yes activity, similar to that of Src, was 10-20 fold higher in three of five colon carcinoma cell lines and fivefold higher in 10 of 21 primary colon cancers than that in normal colonic cells. Lck activity was present in COLO 205 cells, otherwise Lck, Fyn, Hck, Lyn and Fgr activities were not detected in any of the carcinoma cell lines or cancers tested. Increased Yes activity, like that of Src, was due mostly to increased protein levels and not to an apparent decrease in phosphorylation of Tyr 537, the major mechanisms known to deregulate enzymatic activity. Only those colon carcinoma cell lines with elevated Src and/or Yes tyrosine kinase activity as measured in vitro had elevated levels of three tyrosine-phosphorylated proteins as measured in vivo. Thus, colon carcinoma cells contain active tyrosine kinases and/or inactive tyrosine phosphatases not present in normal colonic cells, and Src and Yes appear to be active kinases in the carcinoma cells. These data, together with those demonstrating decreased Src activity in fully differentiated enterocytes, suggest that down regulation of Src-related tyrosine kinases is important for differentiation, and/or deregulation of the kinases is important for growth and transformation of intestinal epithelial cells.

Amino Acid Sequence↗
PubMed1993

[Studies on the alkaloidal components of Polygala tenuifolia willd].

1-Carbobutoxy-beta-carboline, N9-formylharman, 1-carboethoxy-beta-carboline, 1-carbomethoxy-beta-carboline, perlolyrine, harman and norharman were isolated from the rhizoma of Polygala lenuifolia. The structures were elucidated on the basis of spectroscopic studies and chemical evidence, 1-carbobutoxy-beta-carboline has not been seported before.

Alkaloids↗
PubMed1992

Interaction of thioredoxin with oxidized aminobutyrate aminotransferase. Evidence for the formation of a covalent intermediate.

Pig brain 4-aminobutyrate aminotransferase is inactivated by pre-incubation with pyrroloquinoline quinone (2,7,9-tricarboxy-1H-pyrrolo[2,3,f]quinoline- 4,5-dione; PQQ) at pH 7. The reaction of approximately 2 SH residues/dimer is sufficient to inactivate the enzyme. Reoxidized aminotransferase is reactivated by E. coli thioredoxin. Similar results were obtained with E. coli 4-aminobutyrate aminotransferase. The spectroscopic properties of thioredoxin, tagged with the fluorescence probe, anthraniloyl, were used to monitor its interaction with re-oxidized 4-aminobutyrate aminotransferase. During the regeneration of native aminotransferase by thioredoxin, the substrate forms a covalent intermediate with the oxidoreductase, as revealed by gel filtration chromatography. It is postulated that the substrate (oxidized aminotransferase) forms a covalent intermediate with thioredoxin through disulfide linkages.

4-Aminobutyrate Transaminase↗
PubMed1992

Brain 4-aminobutyrate aminotransferase. Isolation and sequence of a cDNA encoding the enzyme.

4-Aminobutyrate aminotransferase is a key enzyme of the 4-aminobutyric acid shunt. It is responsible for the conversion of the neurotransmitter 4-aminobutyrate to succinic semialdehyde. By using oligonucleotide probes based on partial amino acid sequence data for the pig brain enzyme, several overlapping cDNA clones of 2.0-2.2 kilobases in length have been isolated. The largest cDNA clone was selected for sequence analysis. The amino acid sequence predicted from the cDNA sequence shows that the precursor of 4-aminobutyrate aminotransferase consists of the mature enzyme of 473 amino acid residues and an amino-terminal segment of 27 amino acids attributed to the signal peptide. The cofactor pyridoxal-5-P is bound to lysine residue 330 of the deduced amino acid sequence of the mature enzyme.

4-Aminobutyrate Transaminase↗
PubMed1992

The effects of probenecid on the excretion kinetics of stanozolol, an anabolic steroid, in rats.

The pharmacokinetic behaviour and the mechanism of renal excretion of stanozolol (STZ), as affected by co-treatment with probenecid, were studied in male Sprague-Dawley rats. Pharmacokinetic parameters following intravenous (i.v.) administration of STZ (20 mg kg-1 body wt.) were measured in both STZ-treated (control) and STZ plus probenecid-treated (treatment) groups. In order to assess the renal clearance of STZ, bolus doses of STZ and inulin (40 mg kg-1 body wt.) were injected i.v. either in the presence or absence of probenecid (40 mg kg-1 body wt.). The blood and urine concentrations of STZ were determined by capillary gas chromatography-mass spectrometry (GC-MS). In the probenecid treatment group, the area under the plasma disappearance and urinary excretion curves (AUC) of STZ were significantly decreased (P < 0.01) and the volume of distribution (Vd) and total clearance (CLt) were significantly increased statistically (P < 0.05 and P < 0.01, respectively). No remarkable differences in the urine flow rate, urine pH values, glomerular filtration rate (GFR) or renal clearance were observed in the treatment group. However, the clearance ratio in the treatment group was significantly increased from 11.72 to 17.27. From these results, it is suggested that the significant decrease of AUC, i.e. increase of disappearance of STZ in plasma by co-administration with probenecid, is due to the increase of the clearance ratio.

Animals↗
PubMed1992

Effects of growth factors, hormones, bacterial lipopolysaccharides, and lipotechoic acids on the clonal growth of normal ureteral epithelial cells in serum-free culture.

In vitro tissue culture techniques were employed to study the effects of bacterial endotoxins on the growth of normal epithelial cells from the human ureter (NHU). Primary cultures of NHU cells were initiated from explant outgrowth cultures of human ureteral tissue and cultured on collagen gel in F-12* medium containing 1% fetal calf serum (FCS). Optimal clonal growth of secondary cultures of NHU cells seeded at relatively low seeding cell densities, directly on plastic dishes, was achieved in F-12* medium containing bovine pituitary extract (0.5% BPE) and 0.05% BSA. Results indicated that insulin in the F-12* medium could be replaced by three orders of magnitude less IGF-1. Further clonal growth experiments demonstrated that PGE1 is growth stimulatory and can replace BPE as a growth factor requirement. This finding was in agreement with the fact that BPE growth requirement could be replaced by cholera toxin or dibutyryl cAMP. These results suggested that both BPE and cholera toxin operated by activation of a cAMP-dependent mitogenic pathway. Seven gram-negative bacterial lipopolysaccharides (LPS) and three gram-positive bacterial lipotechoic acids (LT) were tested for their effects on NHU clonal growth. Three out of the five LPS derived from Escherichia coli (strains 055:B5, 0128:B12, and 0127:B8), LPS from Klebsiella pneumoniae, and LPS from Pseudomonas aeruginosa all showed significant growth inhibitory effects at minimally effective doses ranging from 5 to 25 micrograms/ml. LPS derived from E. coli strain (0111:B4) had no growth effects at the highest concentration tested (100 micrograms/ml). In contrast, LT derived from Streptococcus pyogenes, S. faecalis, Staphylococcus aureas, and Bacillus subtilis all markedly enhanced clonal growth at concentrations ranging from 1 microgram/ml less than [LT] less than 50 micrograms/ml. LT from Strep. pyogenes was inhibitory to clonal growth at 100 micrograms/ml. The growth inhibitory effects of LPS were shown to be sensitive to the presence of hydrocortisone in the growth medium, indicating that LPS effects on growth are mediated via the arachidonic acid cascade. We speculate that these results indicate a link between the susceptibility of uroepithelial tissue to the pathogenic microflora seen in urinary tract diseases and the differential sensitivity of proliferation-competent uroepithelial cells to growth inhibition by LPS produced by gram-negative bacteria. However, further studies with uropathogenic serotypes will be necessary to corroborate this possibility. The growth-stimulating activity of LTs produced by gram-positive bacteria may be due to their ability to bind to cell-associated fibronectin and to activate the fibronectin receptor as part of ligand receptor-induced mitogenic transmembrane signalling pathway.

Cell Division↗
PubMed1992

Renal cell carcinoma treated with continuous-infusion interleukin-2 with ex vivo-activated killer cells.

High-dose recombinant interleukin-2 (rIL-2) results in tumor responses in patients with metastatic renal cell carcinoma ranging from 9 to 31%. Continuous infusion regimens of rIL-2 may be less toxic and may result in greater in vivo lymphokine-activated killer (LAK) cell production. The current trial used a continuous infusion of rIL-2 with ex vivo LAK cells. These cells were pretreated with phenylalanine methyl ester to remove monocytes to allow cell culture at higher concentrations. Twenty-three patients were entered into the trial. Two patients had complete responses (9%) lasting 15+ and 20+ months. Four patients had partial responses (17%) of 9+, 6+, 3, and 3 months, respectively. One partial responder at 9+ months had only minimal residual retroperitoneal disease that may represent scar tissue. All responders had prior nephrectomies. All but one of the responding patients completed a full cycle of rIL-2 at the highest (starting) dose, 6 x 10(6) U/m2. This rIL-2/LAK regimen appears to be an effective therapy for metastatic renal cell carcinoma.

Adult↗
PubMed1992

Systemic antibiotic prophylaxis in penetrating ocular injuries. An experimental study.

Intraocular concentrations of systemically administered gentamicin and cefazolin in eyes after a standard penetrating ocular injury were measured to determine the effect of eye injury on ocular pharmacokinetics. Twenty pigmented rabbits were divided into two groups. A standard, 8-mm wound was made at the pars plana of one eye in each animal. Group 1 consisted of 10 rabbits that were treated with cefazolin (75 mg/kg), and Group 2 consisted of 10 rabbits that were given gentamicin (2 mg/kg). Fellow eyes, which sustained no trauma, served as control eyes. All groups received intravenous injections every 8 hours for 72 hours, beginning immediately after repair of the wound. After 72 hours, samples were obtained from the anterior chamber, vitreous cavity, and serum. Standardized bioassays for detection of gentamicin or cefazolin were performed. Significant concentrations of intravitreal cefazolin (9.6 micrograms/ml) and gentamicin (0.60 micrograms/ml) were found in the traumatized eyes in comparison to control eyes (P = 0.0001; P = 0.006). Cefazolin exhibited excellent penetration, achieving concentrations well above minimum inhibitory concentration values for most organisms. Gentamicin levels, however, were well below acceptable therapeutic levels. This study suggests that systemically administered cefazolin can achieve significant intravitreal penetration at minimum inhibitory concentrations after penetrating injury.

Animals↗
PubMed1992

L-arginine-dependent killing of intracellular Ehrlichia risticii by macrophages treated with gamma interferon.

Thioglycolate-induced murine peritoneal macrophages infected with Ehrlichia risticii and treated in vitro with gamma interferon (IFN-gamma) developed antiehrlichial activity that eliminated the intracellular bacteria. This antiehrlichial activity was suppressed by NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthesis from L-arginine, but not by L-tryptophan. Increased levels of nitrite, an oxidative product of nitric oxide, were measured in cultures of infected macrophages treated with IFN-gamma. Sodium nitroprusside, which spontaneously releases nitric oxide, also showed the antiehrlichial activity. The antiehrlichial activity by reactive nitrogen intermediates was not mediated by elevation of the cellular concentration of cyclic GMP since the addition of 8-bromo-cyclic GMP itself had no influence on ehrlichial infection of macrophages. Addition of the intracellular iron chelator deferoxamine also inhibited E. risticii infection in vitro. These results suggest that intracellular E. risticii survival is iron dependent and that production of reactive nitrogen intermediates triggers iron loss from critical target enzymes of E. risticii, leading to lethal metabolic inhibition. However, addition of excess FeSO4, ferric citrate, or iron-saturated transferrin did not counteract the antiehrlichial effect induced by IFN-gamma.

Animals↗
PubMed1992

The nonmyristylated Pr160gag-pol polyprotein of human immunodeficiency virus type 1 interacts with Pr55gag and is incorporated into viruslike particles.

The expression of the pol gene of human immunodeficiency virus type 1 occurs via a ribosomal frameshift between the gag and pol genes. The resulting protein, a Gag-Pol polyprotein, is produced at a level 5 to 10% of that of the Gag protein. The Gag-Pol polyprotein is incorporated into virions and provides viral protease, reverse transcriptase, and integrase, which are essential for infectivity. It is generally believed that the Gag-Pol polyprotein is incorporated into virions via interaction with the Gag protein, although the details of the mechanism are unknown. To further study this problem, we have constructed a human immunodeficiency virus type 1 proviral genome which overexpresses the Gag-Pol polyprotein (Pr160gag-pol). Transfection of this proviral genome (pGPpr-) into COS-1 cells resulted in the expression of full-length Pr160gag-pol polyprotein. Although the majority of the Pr160gag-pol was confined to the cells, low levels of reverse transcriptase activity were detectable in the cell supernatants. The cotransfection of pGPpr- with a second plasmid which expresses only the Pr55gag precursor (pGAG) resulted in a significantly higher level of Pr160gag-pol in the medium of transfected cells. Sedimentation analysis using sucrose density gradients demonstrated that most Pr160gag-pol was found in fractions corresponding to the density of virion particles, indicating that the Pr160gag-pol polyprotein was released in association with a Pr55gag viruslike particle. To further characterize the requirements for the release, a mutation was constructed to express an unmyristylated Pr160gag-pol polyprotein. Coexpression with Pr55gag demonstrated that the unmyristylated Pr160gag-pol was also incorporated into virion particles. Subcellular fractionation experiments revealed that the distributions of the Pr160gag-polmyr- and Pr160gag-pol in the membrane and cytosol were similar under low- or high-ionic-strength conditions. Taken together, these results suggest that myristylation of the Pr160gag-pol polyprotein is not required for the interaction with the Pr55gag necessary for packaging into a viruslike particle.

Base Sequence↗
PubMed1992

Pyrroloquinoline quinone (coenzyme PQQ) and the oxidation of SH residues in proteins.

Pyrroloquinoline quinone (PQQ) catalyzes the oxidation of cysteamine at neutral pH with a second order rate constant K2 = 0.45 M-1 s-1. The reduction of PQQ was monitored by absorption and fluorescence spectroscopy, whereas the oxidation of cysteamine to cystamine was followed by titration with 5,5'-dithiobis(2-nitrobenzoic acid). PQQ also catalyzes the oxidation of thiol groups critically connected with the function of two proteins, i.e. thioredoxin and phosphoribulose kinase. The reaction of PQQ with reduced thioredoxin brings about the oxidation of two thiol groups of the oxireductase, whereas the enzyme phosphoribulose kinase is inactivated at 25 degrees C. The oxidized disulfide bond of phosphoribulose kinase is reduced by dithiothreitol and the enzyme recovers catalytic activity. The ability of PQQ to catalyze the oxidation of vicinal cysteinyl residues to generate disulfide bonds under mild experimental conditions can be exploited to define the precise role of modified thiol residues in either catalysis or stabilization of protein structure.

Catalysis↗
PubMed1992

Effect of low neutral endopeptidase expression on response to fMLP.

The effects of the low neutral endopeptidase (24.11/CD10) exhibited by cord blood neutrophils on response to the peptide mediator of cell function f-met-leu-phe (fMLP) were investigated. Oxidative radical release (superoxide and hydrogen peroxide) and chemotactic responses to fMLP were determined and compared to the responses of normal adult neutrophils. The effect of fMLP on CD10 expression as measured by flow cytometry also was evaluated. The data show that cord blood neutrophils produce increased amounts of O2- and H2O2 largely because of a prolonged reaction time to fMLP. In addition, adult polymorphonuclear neutrophil leukocytes increase the intensity of their expression of CD10 following fMLP stimulation, whereas cord blood CD10 expression does not change. Evaluation of chemotaxis demonstrated that cord blood neutrophils exhibited a shift in the fMLP dose-response relationship showing relatively better chemotaxis to lower concentrations. In support of this observation, the inhibition of endopeptidase on adult polymorphonuclear neutrophils leukocytes by phosphoramidon was associated with an augmentation of chemotaxis to 10(-9) and 10(-10) mol/L fMLP. These studies demonstrate that cord blood and adult neutrophils respond differently to fMLP and suggest that membrane endopeptidase plays a role in the observed response patterns. The low level of expression of CD10 on cord blood neutrophils and the failure to increase its expression after fMLP stimulation suggests that adult neutrophils have preformed intracellular CD10 that is not present in the newborn. We propose that the lack of endopeptidase on cord blood neutrophils together with other known features of immaturity may play a role in the overall compromised host defense exhibited by the newborn.

Adult↗
PubMed1991

Sucrose octasulfate stimulates gastric somatostatin release.

To explore the mechanisms of the effects of sucralfate on the stomach, we investigated the action of sucrose octasulfate (SOS), a constituent of sucralfate, on the function of canine gastric parietal cells and somatostatin cells and in the isolated perfused intact rat stomach. Somatostatin cells from the canine gastric fundus were isolated by EDTA-collagenase dispersion and counterflow elutriation, and somatostatin-like immunoreactivity (SLI) release in response to SOS was measured by radioimmunoassay. Similar methods were used to isolate gastric parietal cells, in which gastric acid secretion was measured by uptake of a radiolabeled weak base, [14C]aminopyrine. SLI release by the intact rat stomach was examined in an isolated vascularly perfused rat stomach model. SOS, either alone or co-administered with epinephrine or gastrin heptadecapeptide (G17), dose-dependently stimulated SLI release by isolated canine fundic D-cells. At the highest doses, SOS potentiated the effect of epinephrine but not G17. Similarly, SOS potentiated the stimulating effect of dibutyryl cyclic adenosine 3',5'-monophosphate (DBcAMP), but not 12-O-tetradecanoylphorbol 13-acetate (TPA). The effect of SOS on SLI release could be inhibited by octreotide, a somatostatin analogue. SOS did not alter acid secretion by cultured canine parietal cells either in the basal state or when coadministered with acid secretagogues. In isolated perfused rat stomach studies, SOS produced a significant (60% greater than basal) increase in SLI secretion. There was a similar effect when SOS was perfused against a background of isoproterenol. SOS stimulates SLI release from gastric somatostatin cells and from the isolated perfused stomach but has no direct effect on gastric parietal cells. These actions of SOS may mediate in part the apparent ability of sucralfate to enhance gastric mucosal defense.

Aminopyrine↗
PubMed1991

DNA methylation of two X chromosome genes in female somatic and embryonal carcinoma cells.

The extent of methylation of DNA sequences upstream and within the two X-linked genes, Pgk-1 and Hprt, was analyzed in male and female somatic cells and in female embryonal carcinoma cells carrying either two active X chromosomes (Xa) or one active and one inactive X chromosome (Xi). Sites upstream and within the first intron of both Pgk-1 and Hprt were heavily methylated on the Xi in somatic cells and in embryonal carcinoma cells with an Xi. Reactivation of this Xi was accompanied by extensive demethylation of these sites. In female embryonal carcinoma cells with two active X chromosomes, one X inactivates during differentiation in culture; however, methylation did not occur during differentiation, consistent with the idea that DNA methylation does not play a role in the initiation of X inactivation but may be involved in maintaining inactivation of those genes on the Xi.

Animals↗