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Biomedical subjects

S Wu

Publications and source records attributed to S Wu.

At least 19 recordsLinked to original sources
PubMed1992

Renal cell carcinoma and natural killer cells: studies in a novel rat model in vitro and in vivo.

The transplantable rat kidney carcinoma (RKC) provides an excellent experimental model for immunological and therapeutic studies of renal cell carcinoma. In this report, we define the biological characteristics of RKC and explore the interactions between RKC and natural killer (NK) cells. RKC, a transplantable tumor of spontaneous origin, grows progressively over a 12-week period and metastasizes to the lung when implanted orthotopically in the kidneys of female Lewis rats. Rats bearing RKC survived for an average of 10.5 +/- 1.5 (SD) weeks postimplantation. Lung metastases were visible between 7.5 and 8.5 weeks postimplantation, and by 9 to 10 weeks the incidence of metastases reached approximately 67%. Injection of the NK cell-specific monoclonal antibody 3.2.3 depleted Lewis rats of their NK activity for up to 14 days. Adherent lymphokine-activated killer cells generated from the spleens of 3.2.3-injected rats were significantly less lytic than those from control rats and contained a significantly lower percentage of 3.2.3+ cells when analyzed by flow cytometry. Groups of rats were implanted with RKC and received injections of 3.2.3 biweekly to maintain depletion of NK cells or of a control antibody, NK1.1, specific for mouse NK cells. At 10 weeks postimplantation, 3.2.3-injected rats had significantly (P < or = 0.005) larger tumors (104.4 +/- 20.1 g) than NK1.1-injected rats (75.4 +/- 13.9 g). Spleen cells and peripheral blood cells from uninjected, tumor-bearing rats had a slight but nonsignificant decrease in NK activity against 51Cr-labeled YAC-1 targets over the course of RKC progression. The activity of adherent lymphokine-activated killer cells from tumor-bearing rats was lower than that from normal rats, but not significantly. Cultured RKC cells were killed by both splenic NK cells and adherent lymphokine-activated killer cells. These data demonstrate that RKC is NK sensitive and that tumor growth does not abrogate NK activity. The RKC tumor provides a model system for the analysis of immunological factors in renal cell carcinoma growth and presents opportunities for testing therapeutic interventions in a system that closely mimics the human disease.

Animals↗
PubMed1992

Equilibrium, kinetic, and footprinting studies of the Tus-Ter protein-DNA interaction.

Arrest of DNA replication in the terminus region of the Escherichia coli chromosome is mediated by protein-DNA complexes composed of the Tus protein and 23 base pair sequences generically called Ter sites. We have characterized the in vitro binding of purified Tus protein to a 37-base pair oligodeoxyribonucleotide containing the TerB sequence. The measured equilibrium binding constant (KD) for the chromosomal TerB site in KG buffer (50 mM Tris-Cl, 150 mM potassium glutamate, 25 degrees C, pH 7.5, 0.1 mM dithiothreitol, 0.1 mM EDTA, and 100 micrograms/ml bovine serum albumin) was 3.4 x 10(-13) M. Kinetic measurements in the same buffer revealed that the Tus-TerB complex was very stable, with a half-life of 550 min, a dissociation rate constant of 2.1 x 10(-5) s-1, and an association rate constant of 1.4 x 10(8) M-1 s-1. Similar measurements of Tus protein binding to the TerR2 site of the plasmid R6K showed an affinity 30-fold lower than the Tus-TerB interaction. This difference was due primarily to a more rapid dissociation of the Tus-TerR2 complex. Using standard chemical modification techniques, we also examined the DNA-protein contacts of the Tus-TerB interaction. Extensive contacts between the Tus protein and the TerB sequence were observed in the highly conserved 11 base-pair "core" sequence common to all identified Ter sites. In addition, protein-DNA contact sites were observed in the region of the Ter site where DNA replication is arrested. Projection of the footprinting data onto B-form DNA indicated that the majority of the alkylation interference and hydroxyl radical-protected sites were arranged on one face of the DNA helix. We also observed dimethyl sulfate protection of 2 guanine residues on the opposite side of the helix, suggesting that part of the Tus protein extends around the double helix. The distribution of contacts along the TerB sequence was consistent with the functional polarity of the Tus-Ter complex and suggested possible mechanisms for the impediment of protein translocation along DNA.

Alkylation↗
PubMed1992

Effect of helium-neon laser irradiation on serum lipid peroxide concentrations in burnt mice.

The effect of helium-neon irradiation on serum lipid peroxide concentrations in mice following 6-7% body surface area burns was investigated in a controlled study. Immediately following injury by an 8-sec 100 degrees C scalding, 25 mice were irradiated by a helium-neon laser at 0.05 J/cm2. A control group of the same size underwent identical treatment but received only sham irradiation. Serum lipid peroxide concentrations increased markedly in the control group at 0.5-4 h (P less than 0.0001, two sample t-test). In the laser treated group, the lipid peroxide concentrations remained relatively constant and were significantly depressed relative to the control group 4 h following burning (P less than 0.0001, two-sample t-test).

Animals↗
PubMed1992

Stimulation of ovarian tumor cell proliferation with monocyte products including interleukin-1, interleukin-6, and tumor necrosis factor-alpha.

OBJECTIVE: We investigated whether monocyte-derived factors could stimulate the growth of ovarian cancer cells. STUDY DESIGN: Human peripheral blood monocytes or human monocyte-like cell lines THP-1 and U-937 were cultured with or without macrophage colony-stimulating factor, lipopolysaccharide, or phorbol myristate acetate. Culture supernatants or recombinant cytokines were assayed for growth stimulation of ovarian cancer cell lines by tritium-thymidine incorporation and direct cell counts followed by statistical analysis with Student t test. RESULTS: Conditioned medium from peripheral blood monocytes or from THP-1 or U-937 cells stimulated ovarian cancer cell growth. Interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6 also stimulated ovarian cancer cell growth, whereas macrophage, granulocyte, and granulocyte-macrophage colony-stimulating factor did not. Concentrations of tumor necrosis factor, interleukin-1, and interleukin-6 in conditioned medium could not account for all the growth stimulation, and activity remained after neutralization of tumor necrosis factor, interleukin-1, and interleukin-6 with antibodies. CONCLUSIONS: Interleukin-1, interleukin-6, tumor necrosis factor, and additional monocyte factor(s) could provide paracrine growth stimulation when monocytes are attracted to ovarian cancers that produce macrophage colony-stimulating factor.

Cell Division↗
PubMed1992

Clinical trial on termination of early pregnancy with RU486 in combination with prostaglandin.

Termination of early pregnancy was performed in 1572 healthy women with RU486 (mifepristone, 600mg orally once), followed 36-60 hours later by administration of methyl ester of dl-15-methyl-PGF2 alpha (PG05, 1mg vaginal suppository). Complete abortion was accomplished in 91.2% (1433/1571), incomplete abortion in 4.8% (76/1571), and continued pregnancy in 3.9% (62/1571). The time elapsed between RU486 intake and complete expulsion was 2.4 +/- 1.3 days. Expulsion took place on the third day in 935 women (72%), and on the 4th day in 273 women (21.0%). Uterine bleeding occurred on the second or third day after RU486 intake in 1256 women (88.8%), and lasted 11.7 +/- 6.4 (SD) days, range 2-55 days. One subject had blood transfusion due to excessive bleeding. The main side effects were nausea/vomiting (22.3%), abdominal pain (10.2%), headache/dizziness (4.1%) and diarrhea (2.8%). Fatal side effects have not been reported in this study. About 73% of subjects with complete abortion assessed the treatment as good to excellent. Even in the failed cases, 25-42% of subjects considered the treatment as good. Further studies are needed to determine the optimal dose of the RU486 regimen. It should be emphasized that the treatment must be used under close medical supervision in order to monitor the uterine bleeding.

Abortion, Incomplete↗
PubMed1992

Opponent-processing effects on the field spectral sensitivity of pattern-elicited electroretinograms.

Field spectral sensitivities of the pattern-elicited electroretinogram (PERG) were obtained from two subjects using a modified version of Stiles' two-color increment threshold procedure. A 540 nm checkerboard test pattern of 38 degrees dia was alternated at 8 Hz on a uniform adapting field of the same size. Test intensity, field wavelength and field intensity were varied parametrically. The derived field spectral sensitivity does not resemble that of any individual class of cones; it roughly approximates the photopic luminosity function V lambda, but with sensitivity dips at 540 and 600 nm, which may be associated with an adaptation of the red/green (R/G) opponent site. Thus, it is proposed that the PERG reflect activities in both the luminance and the R/G opponent channels.

Color Perception↗
PubMed1992

Effects of tryptophan mutation on the deprotonation and reprotonation kinetics of the Schiff base during the photocycle of bacteriorhodopsin.

The rates of deprotonation and reprotonation of the protonated Schiff base (PSB) are determined during the photocycle of nine bacteriorhodopsin mutants in which Trp-10, 12, 80, 86, 137, 138, 182 and 189 are individually substituted by either phenylalanine or cysteine. Of all the mutants, the replacement of Trp-86, Trp-182, and Trp-189 by phenylalanine and Trp-137 by cysteine is found to significantly alter the rate of the deprotonation, but not that of the reprotonation process. As compared with ebR, the Trp-86 mutation dramatically increases the rate of deprotonation of the PSB while the Trp-182 mutation greatly decreases this rate. Temperature dependence studies on the rate constants of the deprotonation demonstrate that the different energetic and entropic effects of the mutation are responsible for the observed different kinetic behavior of the Trp-86 and Trp-182 mutants as compared with that of ebR. In the case of Trp-86 mutant, a large decrease in both energy and entropy of activation suggests that the mutation of this tryptophan residue opens up the protein structure as a result of eliminating the hydrogen-bonding group on its side chain by a phenylalanine substitution. A correlation is observed between the proton pumping yield and the relative amplitudes of the slow deprotonation component but not with rate constants of the rise or decay process at constant pH. These results are best discussed in terms of the heterogeneity model (with parallel cycle) rather than back reaction model.

Bacteriorhodopsins↗
PubMed1992

Electroretinograms (ERGs) and visual-evoked potentials (VEPs) elicited by pattern displacement.

The relation between the amplitude of visual responses to a checkerboard stimulus and the degree of lateral displacement of the checks was examined across different check sizes with simultaneously recorded electroretinograms (ERGs) and visual-evoked potentials (VEPs). The amplitudes of both the b-wave and the after-potential of the ERG increase linearly with pattern displacement. However, the major components of the VEP (N70 and P100) were smaller than expected from linearity for both small checks with small displacements (thresholding) and for large checks with large displacements (saturation). These results suggest that the ERG is proportional to the number of receptors stimulated, but the VEP reflects neural processes influenced by the spatial structure of the stimulus.

Adult↗
PubMed1992

Inhibitory effect of tetrandrine on lens proteins-induced ocular inflammation in rabbits.

Ocular inflammation was induced by 25 microliters of lens proteins (62.5mg/ml) injected into anterior chamber of the rabbit eye. Tetrandrine (Tet) (50mg/kg ip) and Indomethacin (Ind) (20 mg/kg ip) showed marked inhibition on this ocular inflammation. Maximum inhibition rate of Tet and Ind was 65% and 66% and their anti-inflammation action lasted 5 and 4 h, respectively. In the early phase of ocular inflammation (at 2 h) the total content of prostaglandin E(PGES) in the iris was reduced by Tet and Ind. Ind showed a greater effect than Tet on PGES. Tet also inhibited leukocyte chemotaxis significantly at late phase of inflammation. No significant effect was observed on the IOP recovery following reduction by 20% NaCl iv. Topical instillation of 50 microliters of 2% Tet did not display any inhibition of ocular inflammation. These results indicate that Tet is an effective ocular antiinflammatory agent without producing ocular hypertension. The antiinflammatory mechanism of Tet in early phase (at 2 h) was related to inhibition of PGES synthesis. The relationship between ocular anti-inflammation and calcium antagonism of Tet was discussed.

Alkaloids↗
PubMed1992

Activation of glycolysis with isoproterenol but not digoxin reverses chronic alcohol depression in hamster hearts.

The purpose of this study was to confirm that an agent, which increases diastolic [Ca2+]i, namely digoxin, depresses cardiac performance, mitochondrial activity, and glycolysis in chronic alcohol-treated and myopathic hearts, and that an agent, which lowers diastolic [Ca2+]i, namely isoproterenol, activates cardiac performance, mitochondrial activity, and glycolysis in these animals. Energy levels, glycolysis, mitochondrial activity, hemodynamics, and cAMP were studied in isolated hearts from three groups of animals, i.e., 9-month control hamsters, hamsters given 50% alcohol until 9 months of age, and 6-month-old cardiomyopathic hamsters in heart failure. Isolated hearts were perfused with either a control medium, a medium containing isoproterenol, digoxin, or digoxin + isoproterenol. Measurement of phosphomonoester sugars, and glucose-6-phosphate, were used to assess glycolytic activity. Oxygen consumption was used to analyze mitochondrial activity. All hearts perfused with either isoproterenol or isoproterenol + digoxin showed an increase in developed pressure, rate-pressure-product, and a decrease in end-diastolic pressure. Isoproterenol activated mitochondrial activity and glycolysis in hearts from myopathic and chronic alcohol hamsters. Based on 31P-NMR studies, isoproterenol or isoproterenol + digoxin improved the over-all energy state of hearts from cardiomyopathic hamsters, but not hearts from control and chronic alcohol hamsters. Digoxin alone augmented the rate-pressure-product and oxygen consumption in control hearts but not hearts from myopathic and chronic alcohol hamsters. Digoxin caused an increase in end-diastolic pressure in myopathic and chronic alcohol hearts but not control hearts. Digoxin depressed glycolysis and worsened the energy state in hearts from cardiomyopathic and chronic alcohol hamsters, but not hearts from control hamsters. In conclusion digoxin, but not isoproterenol nor isoproterenol + digoxin, depressed cardiac performance and glycolysis as well as high energy phosphates in cardiomyopathic and chronic alcohol hearts. Isoproterenol added to digoxin negated the adverse effects of digoxin in cardiomyopathic and chronic alcohol hearts.

Animals↗
PubMed1992

Mesangial cell immune injury. Hemodynamic role of leukocyte- and platelet-derived eicosanoids.

The role of leukocytes and platelets and of leukocyte- and platelet-derived eicosanoids in mediating acute changes in renal and glomerular hemodynamics was assessed in a model of antibody-induced mesangial cell injury in the rat. After a single intravenous injection (6 mg/kg) of the monoclonal antibody (ER4) against the mesangial cell membrane antigen Thy 1, significant decrements in glomerular filtration rate (GFR) and renal blood flow (RBF) were observed at 1 h, and were associated with increments in glomerular LC (+) leukocyte counts and in the synthesis of thromboxane (Tx)B2, leukotriene (LT)B4, and 12-hydroxyeicosatetraenoic acid (HETE). In rats with immune leukopenia, the rise in glomerular LC (+) leukocytes and in eicosanoid synthesis were abolished and the fall in GFR and RBF after administration of ER4 were completely ameliorated. Likewise, pretreatment of rats with both a thromboxane synthase and a 5-lipoxygenase inhibitor also blocked the fall in GFR and RBF and the rise in glomerular synthesis of TxB2 and LTB4 produced by ER4 without changing glomerular LC (+) leukocyte counts. Selective inhibition of thromboxane or 5-lipoxygenase alone only partially ameliorated the decrements in GFR and RBF produced by ER4. In animals with immune thrombocytopenia, the elevated glomerular synthesis of 12-HETE and fall in RBF but not GFR was ameliorated after administration of ER4. The ER4 antibody-induced fall in GFR was mainly caused by a marked decrement in the ultrafiltration coefficient, Kf, which was dependent on TxA2 and 5-lipoxygenase products, since pretreatment of animals with a thromboxane receptor antagonist or with a 5-lipoxygenase inhibitor partially ameliorated this decrement. Structural changes such as infiltration of glomerular capillaries by leukocytes and endothelial cell damage may also have accounted for the fall in Kf. These observations indicate that in antibody-mediated mesangial cell injury, infiltrating leukocytes and platelets mediate the changes in renal hemodynamics via synthesis of thromboxane and arachidonate 5-lipoxygenation products.

Animals↗
PubMed1992

Thyroxine sulfate is a major thyroid hormone metabolite and a potential intermediate in the monodeiodination pathways in fetal sheep.

T3 and rT3 production rates in the fetus account for roughly only a third of the total T4 production rate; thus, the fate of the majority of T4 produced in the fetus is unknown (the "T4 disposal gap"). We developed sensitive and specific T4 sulfate (T4S) and T3 sulfate (T3S) RIAs to investigate the roles of these compounds in fetal T4 metabolism. T3, T4, T3S, and T4S were determined in a variety of tissue fluid and/or serum samples obtained from fetal, newborn (n = 6), and adult (n = 6) sheep. Four groups of fetal animals, with gestational ages of 94 days (n = 5), 110-111 days (n = 6), 130-131 days (n = 6), and 145 days (n = 6; term = 150 days), were studied. In addition, type I 5'-monodeiodinase (5'-MDI) activity was quantified in liver and kidney tissues. 5'-MDI activities were lower in 94- to 131-day-old fetuses than in fetuses near term or in newborn animals. Mean serum T3 concentrations increased progressively from 94 days (19 ng/dl) to term (371 ng/dl), while mean T3S and T4S serum concentrations were highest at 130 days gestation (237 and 989 ng/dl), decreasing to term. Serum T3S and T4S concentrations decreased further in newborns and adult sheep. T4S and T3S levels in allantoic fluid were significantly higher than those in urine and amniotic fluid in all fetal age groups studied. T4S levels in bile were high from 94-130 days gestation (873-1006 ng/dl), decreasing by 50% at term (529 ng/dl). T4S concentrations in meconium were 46- to 83-fold higher than those in bile from 94 days gestation to term. In contrast, bile T3S levels increased progressively from 94-145 days gestation (191-605 ng/dl), while meconium T3S levels decreased during the same period (33-14 micrograms/100 g). These data demonstrate that 1) sulfated iodothyronines, particularly T4S, are major thyroid hormone metabolites in the fetus; 2) both T4S and T3S are excreted into bile and urine and concentrated in meconium and allantoic fluid; and 3) the high levels of T4S and T3S in serum and other fluids may reflect lower tissue type I 5'-MDI activities. We speculate that T4S and T3S may be further metabolized to other sulfated metabolites and may account in part for the T4 disposal gap in fetal sheep.

Allantois↗
PubMed1992

Therapeutic effect of andriol on serum lipids and apolipoproteins in elderly male coronary heart disease patients.

The elevated estradiol/testosterone (E2/T) ratio had been proved to be a risk factor for coronary heart disease (CHD) in elderly males and to exert an adverse effect on lipid metabolism. We conducted a randomized cross-over study to determine the effect of Andriol, a new androgenic preparation, on plasma lipids and apolipoproteins. The results showed a significant difference in most parameters between patients receiving Andriol and the control group: in the former, serum T level was elevated significantly (P < 0.001), E2 level was unchanged (P > 0.05) and the E2/T ratio was reduced (P > 0.05). Blood levels of total cholesterol (TC) and triglyceride (TG) were lowered dramatically (P < 0.001) and high density lipoprotein cholesterol (HDL-ch) was raised (P < 0.05), but apolipoprotein-AI (APO-AI) and B (APO-B) levels remained unchanged. No obvious side effect was observed in those who took Andriol.

Aged↗
PubMed1992

The use of blood glucose/cerebrospinal fluid glucose ratio in the diagnosis of central nervous system infection in infants and children.

The diagnosis of bacterial meningitis can be difficult nowadays when antibiotics are freely used in infants and children with fever due to infection, so that a positive smear or culture may be difficult to achieve. In areas where sophisticated methods of diagnosis may be hard to come by, the simple procedure of simultaneously estimating the blood and cerebrospinal fluid (CSF) glucose levels may be helpful in distinguishing bacterial meningitis from viral meningitis. 74 proven cases of bacterial meningitis and aseptic meningitis were investigated prior to treatment. There were 36 cases of bacterial meningitis and 38 cases of aseptic meningitis. The CSF glucose/plasma glucose ratio was calculated for each patient. The cases were divided into two groups; Group A with CSF glucose/plasma glucose ratio of (0.38-2.0) and Group B with CSF glucose/plasma glucose ratio of (0.1-0.35). In Group A, two out of 59 cases died while in Group B, nine out of 15 died (p < 0.01). 44 out of 59 in Group A recovered fully while only two out of 15 in Group B were cured (p < 0.01). It was also found that 54.2% in Group A were admitted in deep coma compared with 86.7% in Group B (p < 0.05) and 25.4% in Group A were admitted with seizures while 66.7% in Group B had convulsion (p < 0.01). Hence, a low CSF glucose/plasma glucose ratio was associated with a poor outcome. The mechanisms responsible for these findings are discussed especially with reference to the blood-brain barrier (BBB).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[Study on radionuclide migrating along the channel].

The study of impedance line along channel had been performed with the radionuclide tracing method in 15 healthy human being and 4 guinea pigs. These images of tracer migrating routes approximately corresponded with classical courses of channel. The study proved that these line-shaped tracer migration were not by the way of lymphatic and blood vessels as well as nerves. This image of radionuclide migrating along channel may used as the guide for the observation of micro-autoradiography. In this study, satisfactory migrating image along the channel was also obtained by 131I instead of 99mTC. So a new way was opened up for both macro- and micro-autoradiographic study.

Adult↗
PubMed1992

[Solid phase clean-up and determination of vesnarinone in plasma by high performance liquid chromatography].

Vesnarinone, a new positive inotropic agent, was synthesized by Tominaga et al of the Otsuka Pharmaceutical Co. Ltd. Institute in 1982. Determination of Vesnarinone plasma level in dogs by reversed-phase HPLC was developed and presented in this paper. A plasma sample preparation was carried out by solid phase cleaned-up through neutral aluminum column (10 x 1 cm I.D.) eluting with methanol. The chromatography consisted of a slim-pack CLC ODS column (150 x 6.0 mm I.D.) with methanol: 1 mmol/L HAc (55:45) as the mobile phase at a flow rate of 0.8 ml/min. Spectrophotometric detection was at 271 nm, and column temperature was at 25 degrees C. Using 3,4-dihydro-6-(4-(4-methoxybenzoyl)-1-piperazinyl)-2 (1H) quinolinone as an internal standard. The cleaned-up procedure is simple, rapid and satisfactory. The detection limit of vesnarinone was 0.5 ng/ml (R/N, 3:1). The calibration curve was liner (r = 0.99998) in the concentration range of 5-500 ng/10 microliters. Within-day and day-to-day precisions (CV%) were 1.56 and 1.98. The recoveries obtained from cleaned-up and spiked plasma samples were up to 86.52 +/- 2.77% and 96.26 +/- 5.46%, respectively.

Animals↗