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S M Yu

Publications and source records attributed to S M Yu.

At least 55 records · Page 3Linked to original sources
PubMed1996

Mechanism of extracellular ATP-induced proliferation of vascular smooth muscle cells.

The mitogenic effect of extracellular ATP was examined in cultured rat aortic smooth muscle cells (VSMCs). ATP, 2-methylthio-ATP, and ADP stimulated [3H]thymidine and [3H]leucine incorporation and cell growth. AMP, adenosine, UTP, and P2x agonists showed little of these effects. Reactive blue 2, a P2Y purinoceptor antagonist, was effective in suppressing the mitogenic effect of ATP and 2-methylthio-ATP, indicating that extracellular ATP-induced VSMC proliferation is mediated by P2Y purinoceptors. The P2Y purinoceptor activation was coupled to a pertussis toxin (PTX)-insensitive G protein (Gq) and triggered phosphoinositide hydrolysis with subsequent activation of protein kinase C (PKC), Raf-1, and mitogen-activated protein kinase (MAPK) in VSMCs. In response to ATP, both 42-and 44-kDa MAPKs were activated, and tyrosine was phosphorylated. Western blot analysis using PKC isozyme-specific antibodies indicated that VSMCs express PKC-alpha, PKC-delta, and PKC-zeta. A complete down-regulation of PKC-alpha and PKC-delta was seen after 24-hr treatment with 12-O-tetradecanoylphorbol-13-acetate. When cells were pretreated with 12-O-tetradecanoyl-phorbol-13-acetate for 24 hr and subsequently challenged with ATP, Raf-1 activation and 42-kDa as well as 44-kDa MAPK tyrosine phosphorylation failed to be induced. These results demonstrate that ATP-induced Raf-1 and MAPK activations involve the activation of PKC-alpha and PKC-delta. P2Y purinoceptor stimulation with ATP also caused accumulation of c-fos and c-myc mRNAs. Both Reactive blue 2 and staurosporine significantly blocked this increase by ATP. In conclusion, the mitogenic effect of ATP seemed to be triggered by activation of the Gq protein-coupled P2Y purinoceptor that led to the formation of inositol trisphosphate and activation of PKC. PKC and, in turn, Raf-1 and MAPK were then activated, leading eventually to DNA synthesis and cell proliferation.

Adenosine Triphosphate↗
PubMed1996

Avoiding serious complications in laparoscopic cholecystectomy--lessons learned from an experience of 2428 cases.

Over a three-and-a-half year period, we performed 2428 cases of laparoscopic cholecystectomy (LC) and encountered 11 cases of serious procedure-related complications, including bile duct injuries in 4 patients, postoperative bleeding requiring laparotomy and haemostasis in 3 patients, bile leakage from the cystic duct stump, jejunal injury related to puncture, intraoperative injury to the duodenum and subdiaphragmatic abscess in 1 patient each respectively. Six patients required re-hospitalisation including 2 patients with pancreatitis, 1 patient with Ascaris cholangitis, 1 patient with residual stone of the common bile duct (CBD) after laparoscopic CBD exploration, 1 patient with a stone in the CBD after LC, and 1 patient with bile leakage from the cystic duct stump and peritonitis. Of the 2428 patients treated, there was only 1 operative mortality. This patient developed frequent episodes of supraventricular tachycardia. She was found to have pnuemonia on the 21st postoperative day and she died. Apart from this, 1 other patient was found to have primary cancer of the liver 1 month after LC. Based on our experience, we think that LC is safe for patients with benign disease of the gallbladder.

Adolescent↗
PubMed1995

Identification of a very early promoter of insect Hz-1 virus using a novel dual-expression shuttle vector.

Very early promoters of viruses control the proper cascade expression of viral genes and are essential for completion of virus life cycles. These promoters are usually rare and weak and do not encode structural proteins. As a result, they are difficult to identify. In order to identify and clone the very early promoters of a large eukaryotic DNA virus, the Hz-1 virus, a novel cloning strategy was applied. This strategy is based on a dual-expression shuttle vector containing a promoter-less lacZ gene. Insertion of eukaryotic promoters upstream permits the efficient expression of LacZ in bacteria cells. The function of the putative promoters was then confirmed by their proper expression in insect cells. The first two productive infection-specific promoters of Hz-1 virus, contained within the shuttle vectors pTSV-2-129 and pTSV-2-49, were cloned from the HindIII-K and HindIII-A fragments of the Hz-1 viral genome, respectively. By primer extension analysis, an immediate and constitutive expression of the promoter in clone pTSV-2-129 was detected after viral infection. Identification of the productive infection-specific promoters has laid down important groundwork for future studies on the molecular mechanism of the transcriptional switch between productive and persistent infections of Hz-1 virus.

Alcohol Dehydrogenase↗
PubMed1995

Endothelium-dependent relaxation of rat aorta by butein, a novel cyclic AMP-specific phosphodiesterase inhibitor.

Butein, isolated from Dalbergia odorifera T. Chen, caused endothelium-dependent relaxation of rat aorta precontracted with phenylephrine. This effect was abolished in endothelium-denuded aorta and in endothelium-intact aorta in the presence of NG-monomethyl-L-arginine, oxyhemoglobin and methylene blue, whereas the effect was unaltered by indomethacin or charybdotoxin. These results indicate that the vasorelaxant effect of butein depended on the endothelium and was mediated by endothelium-derived relaxing factor (EDRF). Incubation of endothelium-intact aorta with butein increased not only cAMP but also cGMP content. Four phosphodiesterase forms were isolated by diethylaminoethyl (DEAE)-Sephacel chromatography from rat aorta. cAMP-specific phosphodiesterase (type IV) activity was potently inhibited by butein with an IC50 of 10.4 +/- 0.4 microM. In contrast, phosphodiesterase I, III and V activities were inhibited by butein above 100 microM. Adenylate cyclase and guanylate cyclase activities were unchanged by butein. These results suggest that the increase of cAMP formation elicited by butein is due to the inhibition of cAMP-specific phosphodiesterase. The specific phosphodiesterase IV inhibitor (rolipram) and V inhibitor (zaprinast) both produced endothelium-dependent relaxations, whereas the phosphodiesterase III inhibitor (trequinsin) produced relaxation of rat aorta independent of the endothelium. In the presence of a functional endothelium, relaxations produced by butein were significantly potentiated by isoprenaline, forskolin, trequinsin and sodium nitroprusside. It is concluded that butein, a novel cAMP-specific phosphodiesterase inhibitor, produced relaxation of rat aorta, an effect dependent on an intact endothelium. The relaxant effect of butein was markedly enhanced by cGMP-elevating agents.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Pharmacological evaluation of N-methyl-actinodaphnine, a new vascular alpha-adrenoceptor antagonist, isolated from Illigera luzonensis.

The pharmacological activity of N-methyl-actinodaphnine, isolated from Illigera luzonensis, was determined by functional and binding experiments with peripheral tissues. In a functional study, N-methyl-actinodaphnine was a simple competitive antagonist of contractions elicited by phenylephrine (pA2 = 7.11) in rat thoracic aorta; it also competitively antagonised the clonidine-induced inhibition of the twitch response of rat vas deferens (pA2 = 5.01). In addition, [3H]inositol monophosphate formation caused by noradrenaline (3 microM) in rat isolated thoracic aorta was concentration dependently inhibited by N-methyl-actinodaphnine (1 and 10 microM); however, it had no effect on cyclic AMP and cyclic GMP contents. Additionally, N-methyl-actinodaphnine had extremely low affinity for thromboxane receptors, prostaglandin receptors, Ca2+ channels, muscarinic receptors, histamine receptors, beta-adrenoceptors, neurokinin and leukotriene receptors in vitro. However, N-methyl-actinodaphnine also possessed 5-hydroxytryptamine (5-HT) receptor blocking activity. Its potency for blocking 5-HT receptors was about 14 times less than that for blocking alpha 1-adrenoceptors. In binding experiments, N-methyl-actinodaphnine displaced biphasically the binding of 0.2 nM [3H]prazosin to cultured A10 cells. The selectivity for alpha 1-adrenoceptor subtypes was also investigated in rat vas deferens and spleens. The contractile response in rat vas deferens to noradrenaline was competitively inhibited by N-methyl-actinodaphnine with a pA2 value of 6.58; N-methyl-actinodaphnine also competitively antagonized the phenylephrine-induced contraction in rat spleen with a pA2 value of 7.38. These results indicate that N-methyl-actinodaphnine is a selective alpha 1-adrenoceptor antagonist. Furthermore, it is more selective for the alpha 1B- than for the alpha 1A-adrenoceptor subtype.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

Mechanism of anti-proliferation caused by YC-1, an indazole derivative, in cultured rat A10 vascular smooth-muscle cells.

An indazole derivative, YC-1, was identified in this study to be capable of reversibly and effectively inhibiting proliferation of rat A10 vascular smooth-muscle cells (VSMCs) in vitro. YC-1 (1-100 microM) dose-dependently inhibited [3H]thymidine incorporation into DNA in rat A10 VSMCs that were synchronized by serum depletion and then restimulated by addition of 10% foetal calf serum (FCS), whereas FCS-induced [3H]thymidine incorporation into rat synchronized endothelial cells was unaffected by this agent. The dose of YC-1 required to cause inhibition of FCS-induced proliferation was similar to that necessary for the formation of cellular cyclic GMP (cGMP). Guanylate cyclase activity in soluble fractions of VSMCs was activated by YC-1 (1-100 microM), whereas cGMP-specific phosphodiesterase activity was unaffected by this compound. The anti-proliferative effect of YC-1 was mimicked by 8-bromo-cGMP, a membrane-permeable cGMP analogue, and was antagonized by KT 5823 (0.2 microM), a selective inhibitor of protein kinase G. The anti-proliferative effect of YC-1 was also antagonized by Methylene Blue (50 microM), a guanylate cyclase inhibitor, and was potentiated by 3-isobutyl-1-methylxanthine (500 microM), a phosphodiesterase inhibitor. These results verified that YC-1 is a direct soluble guanylate cyclase activator in A10 VSMCs, and the anti-proliferative effect of YC-1 is mediated by cGMP. YC-1 still inhibited FCS-induced DNA synthesis even when added 10-18 h after restimulation of the serum-deprived A10 VSMCs with 10% FCS. Flow cytometry in synchronized populations revealed an acute blockage of FCS-inducible cell-cycle progression at a point in the G1/S-phase in YC-1 (100 microM)-treated cells. The inhibition of proliferation by YC-1 was demonstrated to be independent of cell damage, as documented by several criteria of cell viability. In conclusion, YC-1 reversibly and effectively inhibited the proliferation of VSMCs, suggesting that it has potential as a therapeutic agent in the prevention of vascular diseases.

Animals↗
PubMed1995

Tc-99m phytate bone marrow scintigraphy showing multiple areas of focal hyperactivity in a patient with lung cancer. A case report.

Focal hyperactivity indicative of metastases is a rare finding in bone marrow imaging. In a lung cancer patient with multiple bony metastases, the Tc-99m phytate bone marrow imaging revealed multiple focal areas of increased radioactivity corresponding to the bone scan findings. The findings presented are consistent with a previous animal study, which found that phytate distribution was similar to that of diphosphonate in the skeletal system of rats and rabbits. The authors conclude that Tc-99m phytate should not be used as a bone marrow imaging agent. Further studies of Tc-99m phytate bone marrow scintigraphy on human beings are under way.

Aged↗
PubMed1995

Antiproliferative effects of A02011-1, an adenylyl cyclase activator, in cultured vascular smooth muscle cells of rat.

1. The effects of A02011-1, a pyrazole derivative, on the proliferation of rat vascular smooth muscle cells (VSMCs) were examined. 2. A02011-1 (1-100 microM) concentration-dependently inhibited [3H]-thymidine incorporation into DNA in rat VSMCs that were synchronized by 48 h serum depletion and then re-stimulated by addition of foetal calf serum (FCS, 10%), platelet-derived growth factor (PDGF, 10 ng ml-1), 5-hydroxytryptamine (10 microM) or ADP (10 microM). The inhibitory effect of A02011-1 was fully reversible. However, FCS-induced [3H]-thymidine incorporation into rat endothelial cells was unaffected by A02011-1. 3. The concentration of A02011-1 necessary for inhibition of the FCS-induced proliferation was similar to that necessary for adenosine 3':5'-cyclic monophosphate (cyclic AMP) formation. Adenylyl cyclase activity was increased in A02011-1-treated VSMCs, whereas cyclic AMP-specific phosphodiesterase activity was unchanged. 4. A02011-1 was equipotent with forskolin but was more potent than 8-bromo-cyclic AMP against FCS (10%)-induced proliferation. 5. The antiproliferative action of A02011-1 was mimicked by 8-bromo-cyclic AMP, a membrane-permeable cyclic AMP analogue and was antagonized by 2',5'-dideoxyadenosine, an adenylyl cyclase inhibitor and by Rp-cyclic AMPS, a competitive inhibitor of cyclic AMP-dependent protein kinase (PKA) type I and II. 3-Isobutyl-1-methylxanthine (IBMX) caused significant potentiation of the antiproliferative activity of A02011-1. However, Rp-8-bromo-cyclic GMPS and staurosporine did not affect the antiproliferative activity of A02011-1. 6. A02011-1 still inhibited the FCS-induced DNA synthesis even when added 10-18h after restimulation of the serum-starved VSMCs with 10% FCS. Flow cytometry in synchronized cells revealed an acute blockade of FCS-inducible cell cycle progression at a point in the G,/S phase in A02011-1-treated cells. The inhibition of proliferation by A0201 1-1 was shown to be independent of cell damage,as documented by several criteria of cell viability.7. These results indicate that A0201 1-1 inhibition of VSMC proliferation was mediated by cyclic AMP and was due to a delay in the progression from the G1 into S phase of the cell cycle. A02011-1 did not cause cell toxicity and may thus hold promising potential for the prevention of atherosclerosis or vascular diseases.

Adenylyl Cyclases↗
PubMed1995

Vasorelaxant effect of isoliquiritigenin, a novel soluble guanylate cyclase activator, in rat aorta.

1. The vasorelaxant activity of isoliquiritigenin, isolated from Dalbergia odorifera T, was investigated in the phenylephrine-precontracted rat aorta by measuring tension, guanylate and adenylate cyclase activities, guanosine 3':5'-cyclic monophosphate (cyclic GMP) and adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels. 2. Isoliquiritigenin concentration-dependently relaxed rat aorta contracted with phenylephrine, KCl, U-46619, endothelin and 5-hydroxytryptamine, with EC50s of 7.4 +/- 1.6, 10.5 +/- 2.3, 14.3 +/- 3.3, 11.8 +/- 2.0 and 13.6 +/- 3.7 microM, respectively. 3. Isoliquiritigenin caused endothelium-independent relaxation of phenylephrine-precontracted rat aortic rings. Neither NG-monomethyl-L-arginine (L-NMMA) (an inhibitor of the L-arginine-NO pathway) nor oxyhaemoglobin (which binds NO) modified the relaxant effect of isoliquiritigenin. The relaxant action of isoliquiritigenin also persisted in intact aorta in the presence of indomethacin or glibenclamide. However, methylene blue, an inhibitor of soluble guanylate cyclase, abolished relaxation induced by isoliquiritigenin. 4. Incubation of rat aorta with isoliquiritigenin not only increased aortic cyclic GMP content but also caused small increases in aortic cyclic AMP content, and greatly potentiated the increases in cyclic AMP observed in the presence of forskolin. The maximum increase in cyclic GMP by isoliquiritigenin was reached earlier than the increase in cyclic AMP. This result suggests that the increases in cyclic GMP caused by isoliquiritigenin might stimulate the accumulation of cyclic AMP. 5. Concentration-dependent increases in soluble guanylate cyclase activity were observed in isoliquiritigenin (1-100 microM)- or sodium nitroprusside (SNP)-treated rat aortic smooth muscle cells, while adenylate cyclase activity was unchanged in isoliquiritigenin (100 microM)-treated cells. 6. Relaxation and cyclic AMP formation of rat aorta caused by isoliquiritigenin was potentiated in the presence of forskolin (10 nM), which had little effect when given alone. 2',5'-Dideoxyadenosine (DDA,200 microM), an adenylate cyclase inhibitor, diminished the relaxation and cyclic AMP formation of rat aorta by isoliquiritigenin only in the presence of forskolin. DDA did not affect the increases in cyclic GMP formation induced by isoliquiritigenin. These results suggest that elevated levels of cyclic GMP may mediate the majority of the relaxation of the phenylephrine-precontracted aorta induced byisoliquiritigenin, while the synergistic interaction with a low concentration of forskolin depends on an enhanced accumulation of cyclic AMP.7. Relaxation of phenylephrine-precontracted rat aorta and carbachol-precontracted guinea-pig trachea by rolipram (phosphodiesterase, PDE IV inhibitor) was markedly enhanced by isoliquiritigenin, while response to cilostamide (PDE III inhibitor) was not significantly changed by isoliquiritigenin.8. It is concluded that isoliquiritigenin exerts a vasorelaxant effect by activating soluble guanylatecyclase and increasing cyclic GMP. Synergistic effects of isoliquiritigenin and forskolin on muscle relaxation and cyclic AMP accumulation indicate that inhibition of cyclic AMP breakdown by cyclic GMP via the inhibition of PDE III (cyclic GMP-inhibited PDE) is the dominant mechanism.

Aldehyde Reductase↗
PubMed1995

Characterization of the thromboxane (TP-) receptor subtype involved in proliferation in cultured vascular smooth muscle cells of rat.

1. The effects of the thromboxane A2 (TxA2)-mimetic, U-46619, on the proliferation of vascular smooth muscle cells (VSMCs) were examined in a clonal smooth muscle cell line, A10, which was derived from foetal rat aorta. 2. [3H]-U-46619 bound to A10 cells of passages 18-20 (p18-20) with two classes of sites. The high affinity site showed a Bmax of 3.0 +/- 1.8 fmol mg-1 protein with a KD value 1.0 +/- 0.1 nM, while the low affinity site showed a Bmax of 43.0 +/- 6.0 fmol mg-1 protein and KD value of 129.0 +/- 7.9 nM. However, [3H]-U-46619 bound to A10 cells from passages 28-30 (p28-30) at a single class of site with a Bmax 111.0 +/- 9.0 fmol mg-1 protein and a KD value of 175.4 +/- 22.0 nM. 3. Cinnamophilin and SQ29548 inhibited specific [3H]-U-46619 binding to p18-20 A10 cells in a concentration-dependent manner with Ki values of 390.0 +/- 3.2 and 4.6 +/- 1.0 nM, respectively at a high affinity site, and 2.6 +/- 0.2 microM and 310.0 +/- 6.4 nM, respectively at the low affinity site. 4. U-46619 produced isometric contractions of rat aorta in a concentration-dependent manner with an EC50 7.0 +/- 1.2 nM. Cinnamophilin and SQ29548 antagonized U-46619-induced aortic contractions with pA2 values 6.3 +/- 0.1 and 8.2 +/- 0.2, respectively. 5. U-46619 increased [3H]-thymidine incorporation into DNA of p18-20 and p28-30 A10 cells in aconcentration-dependent manner with EC50 values 362.7 +/- 27.0 and 302.5 +/- 20.1 nm, respectively. The U-46619-induced increase of [3H]-thymidine incorporation into DNA of p28 -30 AO0 cells was potentiatedby PDGF (1 ng ml-1) and FCS (1%) and was inhibited by cinnamophilin (10 microM) and SQ29548 (1 microM)with estimated pKB values 5.4 +/- 1.2 and 6.3 +/- 0.9, respectively.6. Cell cycle analysis revealed that U-46619-increased cell cycle progression was primarily due to a rapidtransition from the DNA synthetic (S) to the G2/mitotic (M) phase. Moreover, U-46619 also increasedprotein synthesis and cell numbers in VSMC. All these effects of U-46619 were inhibited bycinnamophilin and SQ29548.7. U-46619 caused phosphoinositide breakdown and increased the intracellular Ca2+ concentration inVSMC, effects which were blocked by cinnamophilin and SQ29548.8 These data indicate there are two U-46619 binding sites in AlO VSMC. The high affinity site is correlated to U-46619-induced vasoconstriction while the low affinity site is correlated to U-46619-mediated VSMC proliferation. These data also reveal that U-46619 stimulates the cell cycle progression in VSMC primarily through a rapid transition from S to G2/M. Since cinnamophilin inhibits TPreceptor-mediated VSMC proliferation, it may thus hold promising potential for the prevention of atherosclerosis or vascular diseases.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Infant mortality in the United States: trends, differentials, and projections, 1950 through 2010.

OBJECTIVES: This study examined long-term trends and differences in infant mortality in the United States from 1950 through 1991 according to race and ethnicity, education, family income, and cause of death. Forecasts are made through the year 2010. METHODS: Log-linear regression models were applied to data from the National Vital Statistics System, National Linked Birth and Infant Death files, the National Maternal and Infant Health Survey, the National Natality Survey, and the National Infant Mortality Survey to model and forecast infant mortality. RESULTS: Dramatic declines in the US infant mortality rate have occurred in the past 4 decades, largely as a result of declines in mortality from pneumonia and influenza, respiratory distress syndrome, prematurity and low birthweight, congenital anomalies, and accidents. Despite the overall reductions, however, substantial racial/ethnic, educational, and income differences in infant mortality still exist. CONCLUSIONS: The long-term downward trend in US infant mortality has not benefited Blacks and Whites equally. The Black/White disparity in infant mortality has not only persisted but increased over time and is not expected to diminish in the near future. Educational inequalities have also widened, and racial disparities have generally increased across all educational levels.

Adult↗
PubMed1995

Scanning electron microscopy of capsaicin-pretreated trachea in the rat during postnatal development.

The morphological changes of the tracheal surface were studied in neonatally capsaicin-pretreated rats by scanning electron microscopy. One week after neonatal capsaicin treatment, a sparse number of ciliated cells were dispersed among the microvilli-covered goblet cells similar to those of the sham-operated rats. Potential ciliated cells (progenitor cells) possessed a few long cilia and many short cilia. The ciliated cells possessed cilia with a smooth surface and a blunt end similar to that of the sham-operated rats. Two weeks after neonatal capsaicin treatment, numerous ciliated cells frequently in clusters were located among large patches of microvilli-covered goblet cells similar to those of sham-operated rats. Furthermore, the blunt ends of cilia and microvilli contained short star-shaped protrusions extending into the lumen of the trachea. One month after neonatal capsaicin treatment, the star-shaped protrusions became longer, and more irregular than those of sham-operated rats. The short cilia of the potential ciliated cells (progenitor cells) also became blunt and irregular in shape. The star-shaped protrusions of the microvilli of the goblet cells became larger and thicker than those observed at two weeks following capsaicin-pretreatment. Two months after neonatal capsaicin treatment, the tracheal surface was lined with a much greater population of the ciliated cells than that at one month. A striking characteristic at this age was that globular mucin-containing secretory products were trapped within the cilia of the ciliated cells. The results of this study suggest that mucus secretion is probably blocked by the capsaicin-pretreatment. Furthermore, the star-shaped protrusions of cilia and microvilli may indicate that the mucociliary clearance mechanism is interfered with by the capsaicin-pretreatment.

Animals↗
PubMed1994

Protracted treatment with phorbol ester modulates J-7 human hepatoma-cell-induced aggregation and coagulation of human platelet-rich plasma.

In heparinized human platelet-rich plasma (PRP), J-7 human hepatoma cells initially induced platelet aggregation; then a clot formed. ADP-scavenger systems, apyrase and creatine phosphate/creatine phosphokinase did not inhibit this tumor-cell-induced platelet aggregation (TCIPA), whereas hirudin and concanavalin A completely blocked it. J-7 cells also shortened the recalcification time of normal and of Factor-VIII- and IX-deficient human plasma, although it was inactive in shortening the recalcification time of Factor-VII-deficient plasma. After treatment with phorbol 12,13-dibutyrate (PDBu) for 5 to 90 min, the aggregation and coagulation abilities of J-7 cells were unaffected. Prolonged treatment of J-7 cells with PDBu but not with alpha-PDBu for 24 and 72 hr resulted in gradual loss of aggregation and coagulation. Staurosporine antagonized the effect of PDBu and restored aggregation and coagulation in J-7 cells. Protracted treatment with PDBu (24 or 72 hr) did not affect adherence of J-7 cells to the extracellular-matrix proteins (i.e., fibrinogen, fibronectin, laminin, vitronectin and collagen types I and IV) or to the surface of plastic culture dishes. The treatment also did not affect J-7 cell detachment from plastic culture dishes. These in vitro results demonstrate that protracted phorbol ester treatment diminishes TCIPA and blood coagulation of tumor cells.

Alkaloids↗
PubMed1994

Over-the-counter medication use among US preschool-age children.

OBJECTIVE: To estimate the prevalence of recent over-the-counter (OTC) medication use in a national sample of preschool-age children. DESIGN: Follow-up survey of a nationally representative sample of 3-year-old children in the US population by telephone or personal interview. PARTICIPANTS: A total of 8145 children whose mothers were interviewed for the 1991 Longitudinal Follow-up to the National Maternal and Infant Health Survey. MAIN OUTCOME MEASURES: Report of any OTC medications given in the past 30 days and the type of medications that the child received. RESULTS: During the past 30 days, 53.7% of all 3-year-old children in the United States were given some OTC medications. Among OTC medication users, the most common medications reported were Tylenol (66.7%) and cough or cold medicine (66.7%). Most respondents reported that recent child illness episodes (70%) were treated with OTC medications. After adjustment for recent child illness, women who were white (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.13 to 1.55), were more educated (OR, 1.58; 95% CI, 1.24 to 2.00), and had higher incomes (OR, 1.75; 95% CI, 1.33 to 2.30) were more likely to have given their child OTC medications. Women without health insurance were also more likely to have given OTC medications (OR, 1.27; 95% CI, 1.04 to 1.55). Provider visits, but not telephone calls, were associated with a reduction in OTC medication usage. CONCLUSIONS: Over-the-counter medications are an important component of health care for treating illness in US preschool-age children. The high prevalence of use has occurred despite the dearth of scientific proof for the effectiveness of certain classes of OTC medications and the risks associated with improper use.

Acute Disease↗
PubMed1994

Thaliporphine selectively inhibits expression of the inducible, but not the constitutive, nitric oxide synthase.

Formation of nitrites/nitrates caused by lipopolysaccharide (LPS) in J774.2 macrophages was inhibited by thaliporphine, an aporphine derivative isolated from the plant Neolitsea konishii K. This inhibition of nitrite synthesis in LPS-stimulated macrophages by thaliporphine was similar to that by cycloheximide, NG-methyl-L-arginine (MeArg) and dexamethasone. Thaliporphine, but not MeArg, inhibited expression of inducible NO synthase without directly affecting enzyme activity. However, thaliporphine did not inhibit nitrite production by NO synthase that had already been induced by prior exposure to LPS for which any possible further induction was inhibited by cycloheximide. In endothelial cells, nitrite formation induced by bradykinin (in the presence of 0.2 mM Ca2+) was inhibited by MeArg. However, incubation of endothelial cells with dexamethasone, cycloheximide and thaliporphine did not affect this Ca(2+)-dependent nitrite production. Thaliporphine (0.1-100 microM) dose-dependently inhibited nitrite accumulation in macrophages stimulated by interleukin-1 beta (IL-1 beta) whereas nitrite formation induced by tumour necrosis factor alpha was not inhibited. LPS-stimulated IL-1 beta synthesis in macrophages was significantly inhibited by thaliporphine, but thaliporphine had only minimal effect on LPS-stimulated IL-1 beta synthesis in endothelial cells. These results demonstrate that thaliporphine inhibits LPS induction of NO synthase expression, and that the mechanism of action of thaliporphine is via inhibition of LPS-stimulated IL-1 beta synthesis in macrophages. In anaesthetized rats subjected to LPS, pretreatment with thaliporphine partially restored the fall in mean arterial pressure and the vascular hyporeactivity to noradrenaline 3 h after LPS injection. In conclusion, thaliporphine selectively inhibited expression of inducible NO synthase, and may thus hold potential for the treatment of endotoxaemia.

Amino Acid Oxidoreductases↗
PubMed1994

Novel gene expression system for plant cells based on induction of alpha-amylase promoter by carbohydrate starvation.

The 5' regulatory region and putative signal sequence of a rice alpha-amylase gene, alpha Amy8, was fused to a bacterial gene encoding beta-glucuronidase (GUS) and introduced into rice, tobacco, and potato via Agrobacterium-mediated transformation systems. Expression of this chimeric gene in suspension cells of transgenic plants was suppressed by the presence of sucrose in the medium and induced by its absence. Induction or suppression of GUS expression in transgenic rice could be reversed by the deprivation or replenishment, respectively, of sucrose in the medium. The expressed GUS fusion protein was translocated to the endoplasmic reticulum, modified by glycosylation, and secreted into the culture medium of transgenic cells. In the presence of a glycosylation inhibitor, tunicamycin, the enzymatically active form of GUS was assembled in the endoplasmic reticulum. The yield of GUS secreted by transgenic cells was estimated to be as high as 40% of total secreted proteins. The reversible induction of the alpha-amylase promoter in culture cells by sugar level in the medium provides an excellent inducible expression system for basic research in plant science. Combination of the alpha-amylase promoter and signal sequence also offers a novel approach for large scale production of low cost, easily purified, secreted recombinant proteins.

Amino Acid Sequence↗
PubMed1994

Cinnamophilin, a novel thromboxane A2 receptor antagonist, isolated from Cinnamomum philippinense.

The pharmacological activity of cinnamophilin ((8R,8'S)-4,4'-dihydroxy-3,3'-dimethoxy-7-oxo-8,8'-neolignan), isolated from Cinnamomum philippinense, was studied in isolated rat aorta, guinea-pig trachea and rabbit platelets. Cinnamophilin was found to be a thromboxane A2 receptor blocking agent in these tissues as revealed by its competitive antagonism of the U-46619 (9,11-dideoxymethanoepoxy-9 alpha,11 alpha-prostaglandin F2 alpha)-induced contraction of rat aorta and guinea-pig trachea and aggregation of rabbit platelets with pA2 values of 7.3 +/- 0.2, 5.2 +/- 0.1 and 6.3 +/- 0.3, respectively. Protection against the irreversible vasoconstriction of rat aorta caused by U-46619 (0.05 microM) was obtained by cinnamophilin (10 microM) but not by caffeine (25 mM). Cinnamophilin (1-15 microM) also possessed voltage-dependent Ca2+ channel blocking action, judging from its antagonism of the high K+ (60 mM)- and Bay K 8644 (0.1 microM)-induced contraction in rat thoracic aorta. Cinnamophilin (30 microM) produced a slight relaxation of noradrenaline (3 microM)-induced tonic contractions, and this relaxing effect was abolished in the presence of nifedipine (1 microM). Nifedipine (10 microM) sufficient to inhibit high K(+)-induced contractions failed to attenuate the contractile response to U-46619. A high concentration of cinnamophilin (100 microM) did not affect the aortic contraction induced by endothelin-1, angiotensin II, carbachol or serotonin. Neither cAMP nor cGMP in rat aorta was increased by cinnamophilin. These results indicate that cinnamophilin is a selective thromboxane A2 receptor antagonist especially in rat aorta, and also possesses voltage-dependent Ca2+ channel blocking properties.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗