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Biomedical subjects

Y C Yang

Publications and source records attributed to Y C Yang.

At least 127 records · Page 7Linked to original sources
PubMed1995

Anti-tumor and anti-angiogenic effects in mice of heparin conjugated to angiostatic steroids.

Heparin-steroid conjugates have been prepared by linking a non-anti-coagulating derivative of heparin, which binds to endothelial cells, to an angiostatic steroid, which suppresses endothelial cell division. One such conjugate, heparin adipic hydrazide (HAH) linked to cortisol, has previously been shown to inhibit both angiogenesis and the growth of solid tumors in mice. In the present study, heparin hydrazide (HH) was linked to tetrahydro S, tetrahydrocortisone and tetrahydrocortisol, which are devoid of glucocorticoid and mineralocorticoid activity and hence were predicted to have low toxicity to animals. The tetrahydro steroid conjugates were compared with the cortisol conjugate for therapeutic effectiveness against solid Lewis lung carcinoma growing in mice. HAH-cortisol reduced tumor growth by up to 75% whereas a simple mixture of HAH and cortisol was not significantly inhibitory. In contrast to HAH-cortisol, the 3 tetrahydro steroid conjugates did not significantly inhibit tumor growth. The differences in anti-tumor properties of the conjugates correlated with their ability to inhibit angiogenesis in a Matrigel implant model in mice. The tetrahydro steroid conjugates did not significantly inhibit angiogenesis whereas HAH-cortisol inhibited angiogenesis by greater than 90%. Therefore, HAH-cortisol is the most effective heparin-steroid conjugate so far developed.

Animals↗
PubMed1995

Interleukin-11 induces complex formation of Grb2, Fyn, and JAK2 in 3T3L1 cells.

Previous studies suggested that interleukin-11 (IL-11) induces the activation of mitogen-activated protein kinase (MAPK) in mouse 3T3L1 cells. However, the mechanisms by which IL-11 activates MAPK remain elusive. Our present results show that IL-11 promotes the formation of the active GTP-bound form of Ras, suggesting that IL-11 actions may be transduced in part through the Ras/MAPK signaling pathway. By immunoblotting and immunoprecipitation, we further demonstrate the association of tyrosine phosphoproteins with Grb2, an adaptor protein serving as a key intermediate for Ras activation. These phosphotyrosine-containing proteins have been subsequently identified to be JAK2, Fyn, and Syp. JAK2 and Fyn are transiently associated with Grb2 upon stimulation with IL-11, suggesting that JAK2 and Fyn may be involved in transducing signals from the IL-11 receptor-glycoprotein 130 to the Ras system through Grb2. Taken together, these results suggest that IL-11-induced interactions of JAK2, Fyn, and Grb2 may not only provide a novel mechanism for the activation of the Ras/MAPK system but also indicate cross-talk among diverse signaling pathways.

3T3 Cells↗
PubMed1995

Syp associates with gp130 and Janus kinase 2 in response to interleukin-11 in 3T3-L1 mouse preadipocytes.

Protein tyrosine phosphorylation and thus dephosphorylation are part of the interleukin (IL)-11 response in mouse 3T3-L1 cells. We report here for the first time the involvement and interactions of the SH2-containing protein tyrosine phosphatase Syp in the IL-11 signal transduction pathway. Addition of IL-11 to 3T3-L1 cells resulted in an increase in the tyrosine phosphorylation of Syp. When cell lysates were precipitated with glutathione S-transferase fusion products of Syp, the C-terminal SH2 domain of Syp was shown to precipitate several proteins of 70, 130, 150, and 200 kDa that were tyrosine phosphorylated in response to IL-11. Reciprocal immunoprecipitation experiments showed that Syp was inducibly associated with both gp130 and Janus kinase 2 (JAK2). A phosphopeptide containing the sequence for a potential Syp binding site (YXXV) was used to compete with the associations of Syp with gp130 and JAK2. The phosphopeptide reduced the Syp association with both gp130 and JAK2. To summarize, Syp has multiple interactions in IL-11 signal transduction. In addition to the IL-11-induced tyrosine phosphorylation of Syp, Syp coprecipitated with gp130, JAK2, and other tyrosine-phosphorylated proteins in response to IL-11. These findings may have extensive significance to IL-11 and related cytokine signal transduction, suggesting new pathways and mechanisms.

3T3 Cells↗
PubMed1995

Heparin inhibits the expression of interleukin-11 and granulocyte-macrophage colony-stimulating factor in primate bone marrow stromal fibroblasts through mRNA destabilization.

Interactions between different cytokines, extracellular matrix components, and various cell types inside the bone marrow microenvironment are believed to play important roles in the regulation of hematopoiesis. We observed that both interleukin-1 (IL-1) and 12-O-tetradecanoylphorbol-13-acetate (TPA) can stimulate the expression of IL-11 and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes in a primate bone marrow stromal fibroblast cell line, PU-34. We also found that IL-1 or TPA-stimulated IL-11 and GM-CSF expression in PU-34 cells can be abolished by heparin, a class of molecules related to extracellular matrix components, glycosaminoglycans. Because the growth inhibitory signals provided by extracellular factors were less understood, the mechanisms of heparin inhibition of IL-11 and GM-CSF gene expression were further investigated. Our data demonstrate for the first time that heparin did not alter the transcription of endogenous IL-11 and GM-CSF genes or an exogenous IL-11 promoter construct containing an AP-1 sequence. Instead, heparin facilitated the degradation of the corresponding mRNAs. Through RNA gel shift assays, heparin-mediated mRNA destabilization was tentatively linked to its competition for mRNA binding proteins both in the cell-free system and in intact cells. Collectively, our findings suggest that varying degrees of heparin inhibition may provide a novel mechanism for the regulation of cytokine expression during the growth and differentiation of different lineages of hematopoietic cells.

Animals↗
PubMed1995

Interleukin-9 induces tyrosine phosphorylation of insulin receptor substrate-1 via JAK tyrosine kinases.

Interleukin (IL)-9 stimulates the proliferation of a variety of hematopoietic lineages through its interaction with a receptor of the cytokine receptor superfamily. In the studies presented here, we have begun to characterize the downstream signaling pathways activated by IL-9. In addition to the activation of JAK1 and JAK3 tyrosine kinases, IL-9, unlike most hematopoietic cytokines but similar to IL-4, induces the tyrosine phosphorylation of a 170-kDa protein that is related to the insulin receptor substrate-1 (IRS-1). We further demonstrate for the first time that IRS-1 is not only associated with JAK1 but also tyrosine phosphorylated and functionally involved in IL-9 signaling in TS1 lymphocytes transfected with the murine IRS-1 cDNA. Cotransfection studies and in vitro experiments directly demonstrate that JAK1, JAK2, or JAK3 is capable of tyrosine phosphorylating IRS-1, suggesting a functional role for these kinases in vivo. Lastly, we demonstrate that IL-9 induces the tyrosine phosphorylation of Stat3 and in this regard differs from IL-4, which triggers tyrosine phosphorylation of Stat6. Taken together, these results strongly suggest that IL-9 and IL-4 utilize common and unique signaling pathways via inducing the similar and distinct tyrosine-phosphorylated proteins.

Animals↗
PubMed1995

Interleukin (IL)-11--mediated signal transduction.

IL-11 is a multifunctional cytokine biologically related to IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF). It has been shown that these cytokines can utilize common signal transducer, gp130. We have demonstrated that Jak tyrosine kinases, MAP kinases and pp90rsk are highly activated by IL-11 and related cytokines. In addition, we have identified pp90rsk as one of the H7 sensitive protein kinases critical for primary response gene expression induced by IL-11. Furthermore, activation of 3CH134 (a MAP kinase phosphatase) gene by IL-11 suggested that a MAP kinase phosphatase may be involved in IL-11-mediated signal transduction. Our data also suggested that tyrosine phosphorylation of Stat91 and related transcriptional factors is involved in IL-11 signaling but is not sufficient for the activation of primary response genes such as JunB, tis11, tis8 and MAP kinase phosphatase in mouse preadipocytes. The understanding of signal transduction pathways mediated by IL-11 and related cytokines may help to define the common and unique biological properties of these growth factors.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Alterations in local cerebral glucose utilization in rats after chronic amphetamine administration without subsequent challenge.

The 2-deoxyglucose (2-DG) method was used to study regional metabolic changes in rats following chronic d-amphetamine treatment without subsequent challenges. Four groups of rats were pretreated (intraperitoneal administration) with d-amphetamine (0, 1, 5, or 10 mg/kg) once per day for 14 days. After a 7-day abstinence period without further challenge, the 2-DG method was used to measure the rates of local cerebral glucose utilization (LCGU). Significant metabolic changes among the four groups were found in five brain regions, including the nucleus accumbens and the lateral habenular nucleus. Another four groups of rats with the same pretreatment regimens, challenged with 5 mg/kg d-amphetamine, were used for behavioral testing. The results showed intense stereotyped behaviors in the 5 mg/kg and the 10 mg/kg groups. In the steady state, however, there were no significant glucose utilization changes in the nigrostriatal system, which is thought to be related to stereotyped behaviors. During steady state, metabolic changes were found in a limited number of brain regions. No difference in LCGU was found in the sensitization-related regions. Further challenges with stimulants may be necessary to investigate the metabolic responses after sensitization.

Animals↗
PubMed1995

Tyrosine phosphorylation and activation of JAK family tyrosine kinases by interleukin-9 in MO7E cells.

Interleukin-9 (IL-9) is a T-cell-derived multifunctional cytokine that can stimulate the proliferation of a human megakaryocytic leukemia cell line, MO7E. Previous studies suggested that protein tyrosine phosphorylation may be involved in IL-9 signaling pathways. However, tyrosine kinases activated by IL-9 have not been identified. In this report we show that IL-9 induces tyrosine phosphorylation and activation of the JAK family tyrosine kinases including JAK1, JAK3, and Tyk2. The kinetic studies indicate that tyrosine phosphorylation and activation of JAK kinases induced by IL-9 occurred within 1 minute, peaked by 5 to 10 minutes, and persisted at least for 45 minutes. Furthermore, we show that signal transducers and activators of transcription (Stat) 91 or related protein and an 88-kD Stat 91-associated protein are rapidly tyrosine phosphorylated following IL-9 treatment. Gel shift assays confirm that nuclear extracts from MO7E cells stimulated with IL-9 specifically interact with a DNA element termed gamma activated site. These results suggest that actions of IL-9 may, in part, be mediated through JAK kinase-Stat signaling cascades.

Base Sequence↗
PubMed1995

Activation of junB and c-myc primary response genes by interleukin 9 in a human factor-dependent cell line.

Interleukin 9 (IL-9) stimulates the proliferation of various hematopoietic cell types. To elucidate the molecular mechanisms underlying the cell proliferation action, immediate-early gene expression elicited by IL-9 in a human factor-dependent cell line, MO7e, was studied. IL-9 stimulation resulted in a rapid and transient elevation of primary response genes including junB and c-myc. The differential effects of protein kinase inhibitors, herbimycin A, genistein, and H-7 on the steady-state mRNA level and the transcription rate of junB and c-myc genes triggered by IL-9 were also investigated. Herbimycin A, but not genistein, specifically inhibited the expression of junB steady-state mRNA and the in vitro transcription of the junB gene. IL-9-enhanced c-myc gene expression was completely inhibited by both herbimycin A and genistein at the level of transcriptional initiation. H-7 failed to inhibit c-myc, but partially abolished junB mRNA induction. The role of protein kinase C in IL-9-mediated junB induction was also examined. The different responses of junB and c-myc messages to protein kinase inhibitors suggested that more than one pathway may be involved in IL-9-mediated signal transduction which leads to the expression of junB and c-myc genes.

Benzoquinones↗
PubMed1995

Laparoscopic para-aortic lymph node sampling in the staging of invasive cervical carcinoma: including a comparative study of 21 laparotomy cases.

OBJECTIVES: To assess the efficacy and risks of laparoscopic para-aortic lymph node sampling compared with standard laparotomy in staging cervical carcinoma. METHODS: From August 1993 through July 1994, 38 patients with biopsy-proven invasive cervical carcinoma (24 early and 14 advanced invasive cancers) were entered into the study. This was a prospective study of laparoscopic para-aortic lymphadenectomy in invasive cervical carcinoma, with patients serving as their own controls. Video laparoscopic lymph node sampling was performed. In patients with early invasive cancer, the nodes were sent for frozen section and, if negative, laparotomy was performed to look for any residual nodes. Radical hysterectomy was performed immediately if residual nodes were negative. Patients with either nodal metastasis on frozen section or with advanced cancer underwent para-aortic lymphadenectomy only. The operative technique was also evaluated. RESULTS: Laparoscopy required an average of 77 min (S.D. 40), with an average blood loss of 116 ml (S.D. 321). The average number of nodes was 15 (S.D. 7). At subsequent laparotomy the average number of residual nodes found was 0.4 (S.D. 0.9) and none showed metastasis. One vena cava laceration and one ureteral injury required immediate repair, and two patients were too obese to undergo laparoscopy. CONCLUSIONS: Laparoscopic para-aortic lymph node sampling is a less invasive, reliable method for staging invasive cervical carcinoma and can substitute for traditional open procedures. The incidence of risks with this method appears to be low.

Aorta↗
PubMed1995

Interleukin-11 induces phosphatidic acid formation and activates MAP kinase in mouse 3T3-L1 cells.

Interleukin-11 (IL-11) stimulated [3H]phosphatidic acid (PA) formation in [3H]arachidonic acid (AA) prelabelled quiescent mouse 3T3-L1 cells. When IL-11 stimulated 3T3-L1 cells were incubated with NaF, a phosphatidic acid phosphohydrolase (PAP) inhibitor, increased PA formation was observed. In the presence of ethanol, phosphatidylethanol accumulated at the expense of PA. These results indicated that the formation of PA upon IL-11 stimulation was a result of phospholipase D (PLD) activation. Endogenous accumulation of PA by NaF treatment or exogenously added PA enhanced tyrosine phosphorylation of two proteins of 44 KDa (p44) and 47 KDa (p47) whereas tyrosine phosphorylation of other proteins was not affected. Among various PA species, dipalmitoyl PA was found to be most effective in enhancing tyrosine phosphorylation of these proteins. p44 and p47 cross reacted with anti-MAP kinase monoclonal antibody (MoAb) in both immunoprecipitation and western blot analysis. Lysates from IL-11-induced or PA-induced cells stimulated phosphorylation of a synthetic peptide substrate for MAP kinase, indicating the activation of MAP kinase in the induced cells. These studies suggest that one of the cellular signalling mechanisms of IL-11 in 3T3-L1 cells involves the activation of phospholipase D to produce the second messenger PA. The increased level of PA enhances tyrosine phosphorylation of p44 and p47 which belong to the members of MAP kinase family and thus transduces some of the mitogenic signals of IL-11 in this cell line.

3T3 Cells↗
PubMed1995

Mini-catheter used for bladder drainage following stress-incontinence surgery and the factors relating to drainage failure.

OBJECTIVES: To determine the most effective length for the mini-catheter and to discuss factors relating to drainage failure. METHODS: Prospective study of a No. 8 silastic feeding tube for bladder drainage omits the necessity of additional catheterization for measuring residual urine. This two-part study in which 146 patients took part, first, determined the suitable length for insertions for the perforated portion and the imperforated portion; then, gauged the effectiveness of the mini-catheter with desired proportions. RESULTS: Drainage is better when the imperforated portion is at least 5 cm in length (p = 0.0129). The length of the perforated portion, on the other hand, has less impact of the resultant drainage provided that its length does not exceed 5 cm. Beyond this length, an obstruction often occurs. There were 2 obstructions (1.3%) induced by blood clot as well as 9 patients (5.8%) who suffered from one, or more, complications attributed to the mini-catheter for reasons other than the length of insertion. CONCLUSIONS: When care is taken in creating a mini-catheter of the proper proportions, it offers many advantages and very few complications to gynecologists and patients alike.

Drainage↗
PubMed1995

Dose-dependent effects of chronic amphetamine administration in local cerebral glucose utilization in rat.

The daily dose of amphetamine pretreatment may affect the development of behavioral-sensitized patterns in rodents and amphetamine psychosis in humans. This experiment investigated the regional cerebral metabolic changes in rats after pretreatment with different doses of amphetamine by the 2-[14C]deoxyglucose method. Rates of local cerebral glucose utilization were examined in 37 regions of the rat brain. The result showed generally maximal metabolic augmentation in the 5.0 mg/kg group instead of in the 1.0 or the 10.0 mg/kg groups. Behavioral testing using motor activity cages in rats with the same regimen found no difference among groups. The findings demonstrate that there might be a window effect by daily amphetamine dose on the development of drug dependence and amphetamine psychosis. It was suggested that the 2(-)[14C]deoxyglucose method could be used for further study of animal models of amphetamine psychosis.

Amphetamine↗
PubMed1995

Acute pancreatitis in pregnancy.

BACKGROUND: Discuss the course of acute pancreatitis in pregnant patients and demonstrate that most attacks of pancreatitis in pregnancy are mild. METHODS: This article is a retrospective case series study. Eight patients with acute pancreatitis during pregnancy were seen in referral-based obstetric practice at our department in the last 5 years. Five of them had either gallstones or hyperlipidemia. Two patients had both gallstones and hyperlipidemia. One patient was lost to follow-up at 33 weeks gestation. The others were followed at least one month post-partum. Conservative treatment was instituted for pancreatitis and a fat-restricted diet was instituted for hyperlipidemia. RESULTS: There was no maternal mortality and only one fetal death. Acute pancreatitis occurred in both primipara and multipara patients. Preterm labor or preeclampsia may occur in pregnancy complicated by acute pancreatitis. Most patients experience relief from the pancreatitis soon after delivery. Two patients underwent cesarean section, one was due to fetal distress and the other was elective. CONCLUSIONS: Early diagnosis and treatment is of utmost importance. Gallstones and/or hyperlipidemia seems to have a specific link with acute pancreatitis in pregnancy. Although acute pancreatitis is a rare complication of pregnancy, we present evidence that both maternal and fetal mortality can be minimized if appropriately treated.

Acute Disease↗
PubMed1995

Infestation rate of head lice in primary school children in Inchon, Korea.

The survey of the head louse infestation of primary school children in Inchon city was carried out in May 26-27, 1995. Total number of the children surveyed were 1,530. Four (0.5%) out of 768 boys were infested with nits or adults/nymphs of lice and 72 (9.4%) out of 762 girls were positive with those of lice. The infestation rate of lice for girls was 19 times higher than that of boys.

Child↗
PubMed1995

Evaluation of the hemostatic clot formation of newborns by Sonoclot coagulation analyzer.

BACKGROUND: Sonoclot Analyzer has been widely used for more than five years in The United States to evaluate the platelet function and coagulation in adult. No clinical trial with the Analyzer has been reported in the field of pediatrics. The present study was aimed to evaluate the efficacy of the Sonoclot Analyzer for urgent determination of platelet function and coagulation in newborns. METHODS: Venous blood samples were drawn from the umbilical vein in 70 healthy newborns, and from the median cubital vein in 70 healthy adult volunteers, between 24 to 40 years of age, for control. DP2951 Sonoclot II Surgical Analyzer with graphic printer was used to evaluate the hemostatic clot formation. RESULTS: Results demonstrated that Sono ACT (activated coagulation time), peak time and retraction time increased by 36%, 66% and 70% respectively in newborns, while clot rate decreased by 69% in comparison with that of these adults. CONCLUSIONS: The results of using the Sonoclot Analyzer in this study confirmed other previous investigation that platelet function and coagulation are altered in newborns when compared with that of adults. The Sonoclot Analyzer is a simple device, easy to perform; It requires only small amounts of blood sampled (0.4 ml), and provides a rapid coagulation function for newborns.

Adult↗