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Biomedical subjects

Y C Yang

Publications and source records attributed to Y C Yang.

At least 181 records · Page 10Linked to original sources

Human interleukin-9: a new cytokine in hematopoiesis.

IL-9 was first identified in the mouse system as a T cell growth factor while human IL-9 was isolated based on its activity on a human myeloid leukemic cell line. The high sequence homology between mouse and human IL-9 plus the preliminary biological analysis have predicted a wide spectrum of in vitro biological activities for this cytokine. Despite the high sequence homology between mouse and human IL-9, many biological activities, however, have not been demonstrated in both species. In vivo studies therefore become essential to understand the physiological role of IL-9. Increasing evidence have also suggested the possible role of IL-9 in the pathogenesis of HD and LCAL. Detailed analysis of IL-9 expression, autocrine growth and clinical outcome of HD patients will be required to make any speculation on the role of this cytokine in the disease states.

Animals↗

Interleukin-11 and its receptor.

Interleukin (IL)-11 is a bone marrow fibroblast derived cytokine with a wide spectrum of activities in different biological systems. It has been shown that IL-11 supports the growth of certain types of plasmacytoma and hybridoma cells, enhances antigen-specific antibody responses, synergizes with IL-3 in supporting megakaryocyte colony formation, acts synergistically with IL-3 in shortening the G0 period of early progenitors, induces the synthesis of acute phase proteins, and inhibits lipoprotein lipase activity and adipocyte differentiation. The human IL-11 gene, which is localized at 19q13.3-13.4, consists of five exons and four introns. Initial biochemical characterization has identified a 151 kDa protein as the potential IL-11 binding subunit of the receptor complex. Because of the overlapping biological activities between IL-6 and IL-11, we compared the signal transduction pathways mediated by IL-6 or IL-11 in cell lines responsive to both cytokines. Results from protein tyrosine phosphorylation and immediate response gene expression suggest that there are convergent and divergent points along the signal transduction pathways utilized by IL-6 or IL-11. The IL-6 signal transducer, gp130, appears to be involved in the IL-11 mediated signaling. Other cytokines such as leukemia inhibitory factor, oncostatin M and ciliary neurotrophic factor have also been shown to utilize gp130 as a signal transducer. The significance of growth factor sharing common biological activities and signaling pathways will be discussed.

Animals↗

[Antihypertensive effects of atenolol and nitrendipine alone or in combination on three hypertensive models of rats].

The antihypertensive effects of atenolol (Ate) or nitrendipine (Nit) alone or in combination (Ate+Nit) were studied in conscious experimental hypertensive rats. The hypotensive effects of single ig of Ate 20 + Nit 10 mg.kg-1 were rapid and persistent in spontaneously hypertensive rats (SHR). In renovascular hypertensive rats (RVHR) and DOCA-salt hypertensive rats (DHR), Ate+Nit (6 + 3, 20 + 10, 60 + 30 mg.kg-1) given ig once a day for 10 d reduced the blood pressure in a dose-dependent manner. But Ate 20 mg.kg-1 or Nit 10 mg.kg-1 alone given ig once a day for 10 d caused no obvious reduction in blood pressure in RVHR, DHR, and SHR q = 1.32. These results revealed that the synergy is present in the antihypertensive action of Ate+Nit.

Animals↗

Prenatal diagnosis of meconium peritonitis--a case report with literature review.

A case of meconium peritonitis that was diagnosed ultrasonographically in the second trimester is presented. Fetal ascites, intraabdominal calcification and polyhydramnios were detected on antenatal ultrasonography. Specks of calcification were also demonstrated on abdominal radiography postnatally. The obstetric and neonatal implications of meconium peritonitis are discussed with literature review.

Adult↗

Human interleukin (IL)-9 specifically stimulates proliferation of CD34+++DR+CD33- erythroid progenitors in normal human bone marrow in the absence of serum.

The cDNA encoding human interleukin (IL)-9 has recently been cloned and the recombinant molecule found to enhance erythroid colony formation in vitro by bone marrow, peripheral blood, and cord blood cells. In our present report, recombinant human (rhu) IL-9 was evaluated, alone and in combination with other cytokines, for its effect on colony formation by erythroid progenitor (erythroid burst-forming units, BFU-E) and precursor (erythroid colony-forming units, CFU-E) cells in low density (LD), nonadherent LD density T-lymphocyte-depleted (NALT-), and immunofluorescence-sorted CD34+++DR+ and CD34+++DR+CD33- cells from normal human bone marrow. When highly enriched CD34+++DR+ and CD34+++DR+CD33- cells were plated at 200 and 100 cells/ml in the presence of 5% (vol/vol) 5637-cell-conditioned medium and erythropoietin (Epo) under serum-containing conditions, 46 and 51 day-14 BFU-E were observed, respectively. The enhancing effect of rhuIL-9 was similar to that of 5637 CM on colony formation by Epo-dependent BFU-E and CFU-E in these enriched sorted CD34+++DR+ and CD34+++DR+CD33- cells under serum-containing and serum-depleted culture conditions. No significant synergistic or additive effect of rhuIL-9 was noted when used in conjunction with rhu interleukin 3 (rhuIL-3), rhu interleukin 6 (rhuIL-6), and/or rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) under the same culture conditions. The cloning enhancing effect elicited by human IL-9 is Epo dependent, although IL-9 alone sustains the survival of erythroid progenitor cells in vitro, as assessed by delayed additions of Epo to the cultures. The ability of human IL-9 to stimulate BFU-E and CFU-E colony formation using low numbers of highly enriched progenitor cells in serum-depleted conditions demonstrates the direct effect of IL-9 on erythroid progenitors and implicates its potential role in the enhancement of erythropoiesis.

Antigens, CD↗

Decreased amniotic fluid index in term pregnancy. Clinical significance.

In a study of 331 term pregnancies a four-quadrant technique was used to obtain amniotic fluid index measurements, and the results were compared with the current widely used single-pocket measurement. In contrast to the "2-cm rule," the amniotic fluid index measurements consistently demonstrated higher sensitivity in predicting poor fetal outcome with no decrease in specificity. It was noted that pregnancies with an index of < or = 8 cm showed higher incidences of meconium staining, cesarean delivery for fetal distress, abnormal fetal heart rate monitoring and Apgar scores of < or = 7 or less at one minute.

Amniotic Fluid↗

[Effects of silybin on acute myocardial infarction and reperfusion injury in anesthetized rats].

The effects of silybin (Sil) on myocardial infarction size and ischemia- and reperfusion-induced arrhythmias were studied in anesthetized open chest Sprague-Dawley rats. It was found that pretreatment with Sil 20, 50, and 80 mg.kg-1 iv reduced significantly infarct size by 34.7%, 35.0%, and 50.6% respectively at 4 h after ligation. Sil prevented ischemic arrhythmia only at the dose of 80 mg.kg-1. In reperfusion experiment, pretreatment with Sil 20 mg.kg-1 decreased significantly reperfusion-induced arrhythmia.

Animals↗

Myeloid differentiation of purified CD34+ cells after stimulation with recombinant human granulocyte-monocyte colony-stimulating factor (CSF), granulocyte-CSF, monocyte-CSF, and interleukin-3.

CD34+ cells isolated from bone marrow or umbilical cord blood from healthy donors were studied for proliferation and differentiation in liquid cultures in the presence of recombinant human granulocyte-monocyte colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), monocyte CSF (M-CSF), and interleukin-3 (IL-3), followed by immunophenotyping for myeloid and myeloid-associated cell surface markers. IL-3, either alone or together with GM-CSF, G-CSF, or M-CSF, induced, on average, 50-fold cell multiplication, GM-CSF five fold to 10-fold, and G-CSF and M-CSF less than fivefold. Cells from cultures stimulated with GM-CSF, G-CSF, or M-CSF alone contained cells with a "broad" myeloid profile, "broader" than observed in cultures with IL-3. However, since IL-3 induced rapid cell multiplication, high numbers of cells expressing early (CD13, CD33) and late myeloid markers (CD14, CD15) were recovered. The presence of other CSFs together with IL-3 did not alter the IL-3-induced effect on the cells. When 5,000 CD34+ cells were cultured with IL-3 alone, the cultures still contained 2,000 to 5,000 CD34+ cells after 14 days of culture, while cells cultured with GM-CSF, G-CSF, or M-CSF contained less than 1,000 CD34+ cells. Furthermore, 1,000 to 3,000 cells were positive for the megakaryocytic lineage marker CD41b after cultures with GM-CSF or IL-3, while cultures with G-CSF or M-CSF did not contain detectable numbers of CD41b+ cells. Finally, erythroid cells could also be generated from purified CD34+ cells. The results show that IL-3 and GM-CSF can induce rapid proliferation of purified CD34+ cells in vitro with differentiation to multiple myeloid lineages, while certain subsets maintain expression of CD34.

Antigens, CD↗

Effect of interleukin-9 on clonogenic maturation and cell-cycle status of fetal and adult hematopoietic progenitors.

We assessed the effect of interleukin-9 (IL-9) on clonogenic maturation and cell-cycle status of hematopoietic progenitors of fetal (umbilical cord blood) and adult (bone marrow) origin. As a single agent IL-9 supported, in a concentration-dependent fashion, maturation of burst-forming units-erythroid (BFU-E) of adult and fetal origin. However, only 1/3 the number of adult BFU-E colonies developed, as did in response to granulocyte-macrophage colony-stimulating factor (GM-CSF), and only 1/6 the number developed as did in response to IL-3. In contrast, the effect of IL-9 on fetal BFU-E colonies was equal to that of GM-CSF and IL-3. Synergistic effects of IL-9 with low concentrations (0.1 ng/mL) of GM-CSF and IL-3 were seen on adult BFU-E colony formation, but no effect was apparent at higher concentrations (1.0 ng/mL). In contrast, using fetal cells, synergistic effects of IL-9 with low and high concentrations of GM-CSF and IL-3 were apparent. Addition of IL-9 to plates containing fetal cells plus GM-CSF and IL-3 not only resulted in more BFU-E colonies, but also in more multicentered (greater than or equal to 10 individual centers) colonies, and more cells per colony. IL-9 had a wider spectrum of action on progenitors of fetal origin than on progenitors of adult origin, supporting the generation of fetal multipotent colony-forming unit (CFU)-Mix and CFU-GM colonies. Incubation with IL-9 did not accelerate cycling of adult or fetal BFU-E, CFU-Mix, or CFU-GM to the extent observed after incubation with IL-6. Thus, IL-9 primarily supported maturation of erythroid progenitors of adult origin, and its addition to plates containing GM-CSF and IL-3 (1.0 ng/mL) did not result in maturation of additional clones. In contrast, IL-9 had a wider spectrum of action on fetal progenitors and, when combined with IL-3 and GM-CSF, resulted in clonogenic maturation of progenitors that did not undergo maturation after stimulation with IL-3 and GM-CSF.

Aging↗

Stromal cell-associated hematopoiesis: immortalization and characterization of a primate bone marrow-derived stromal cell line.

An elucidation of the interaction between the bone marrow microenvironment and hematopoietic stem cells is critical to the understanding of the molecular basis of stem cell self renewal and differentiation. This interaction is dependent, at least in part, on direct cell to cell contact or cellular adhesion to extracellular matrix proteins. Long-term bone marrow cultures (LTMC) provide an appropriate microenvironment for maintenance of primitive hematopoietic stem cells and a means of analyzing this stem cell-stromal cell interaction in vitro. Although LTMC have been successfully generated from murine and human bone marrow, only limited success has been reported in a primate system. In addition, few permanent stromal cell lines are available from nonmurine bone marrow. Because the primate has become a useful model for large animal bone marrow transplant studies and, more specifically, retroviral-mediated gene transfer analysis, we have generated immortalized bone marrow stromal cell lines from primate bone marrow using gene transfer of the Simian virus large T (SV40 LT) antigen. At least one stromal cell line has demonstrated the capacity to maintain early hematopoietic cells in long-term cultures for up to 4 weeks as measured by in vitro progenitor assays. Studies were undertaken to characterize the products of extracellular matrix biosynthesis and growth factor synthesis of this cell line, designated PU-34. In contrast to most murine bone marrow-derived stromal cell lines capable of supporting hematopoiesis in vitro that have been examined, the extracellular matrix produced by this primate cell line includes collagen types I, laminin. Growth factor production analyzed through RNA blot analysis, bone marrow cell culture data, and factor-dependent cell line proliferation assays includes interleukin-6 (IL-6), IL-7, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, leukemia inhibitory factor, and a novel cytokine designated IL-11. This immortalized primate bone marrow stromal cell line may be useful in maintaining early progenitor cells for experimental manipulation without the loss of reconstituting capacity and as a potential source of novel hematopoietic growth factors.

Animals↗

Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells.

We have isolated the genomic sequence of human interleukin-9 (IL-9) based on its sequence homology with a human IL-9 cDNA isolated from human T-cell leukemia virus (HTLV)-I-transformed T cells by expression cloning. The entire genomic sequence has been determined and the gene consists of five exons and four introns. The human IL-9 gene is mapped to the long arm of human chromosome 5 at band 5q31-32, a region found to be deleted in a number of patients with acquired 5q- abnormalities and hematologic disorders. Several blocks of transcriptional control sequences have been identified at the 5'-flanking region of the human IL-9 gene that may play an important role in the control of IL-9 gene expression. The 5'-regulatory region of the human IL-9 gene also contains sequences identified in the 5'-flanking regions of other cytokine genes mapped to the long arm of human chromosome 5, including IL-3, IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor and other T-cell growth factor genes including IL-2 and IL-6. The IL-9 gene is constitutively expressed in the HTLV-I-transformed human T cells and the expression of IL-9 in these cells can be further induced by 12-O-tetradecanoyl phorbol 13-acetate. Transient transfection analysis using the plasmid containing the 5'-flanking region of IL-9 gene upstream from the firefly luciferase ciferase report gene indicated that the 0.9-kb Smal-Sacl fragment of the IL-9 gene contains sequences required for the constitutive and activated expression of IL-9 gene in HTLV-I-transformed cells. These results will now allow us to study the regulatory mechanism of IL-9 gene expression in normal and leukemic human T cells.

Amino Acid Sequence↗

Direct and synergistic effects of interleukin 11 on murine hemopoiesis in culture.

We have examined the effects of a stromal cell-derived cytokine designated interleukin 11 (IL-11) on the proliferation of murine hemopoietic progenitors in methylcellulose culture. COS cell-conditioned medium containing IL-11 supported formation of granulocyte/macrophage colonies and a small number of multilineage colonies including blast cell colonies in cultures of marrow cells from normal mice. When tested with marrow cells harvested 2 days after injection of 5-fluorouracil at 150 mg/kg, IL-11 enhanced interleukin 3-dependent colony formation, whereas IL-11 alone supported only scant colony formation. Serial observations (mapping studies) of cultures of post-5-fluorouracil spleen cells indicated that the mechanism of the synergistic effect of IL-11 is to shorten the dormant period of stem cells, an effect very similar to that of interleukin 6. When pooled blast cells were plated into medium containing IL-11 and erythropoietin, only macrophage colonies were observed. Thus, IL-11 can directly support the proliferation of committed macrophage progenitors and, and like interleukin 6 and granulocyte colony-stimulating factor, act synergistically with interleukin 3 to shorten the Go period of early progenitors.

Animals↗

Allylglycine-induced seizures in male and female rats.

The possibility that a sex difference in gamma-aminobutyric acid (GABA) activity might be an underlying cause of the previously reported sex differences in picrotoxin-induced seizures was investigated. Male and female rats were injected (IP) with the GABA antagonist, L-allylglycine (100, 150, 200, or 250 mg/kg), and observed for behavioral signs of five categories of seizures induced by picrotoxin: myoclonic, focal, generalized tonic extension, generalized clonic, and generalized seizures with tonic and clonic components. The latency to the first occurrence of each seizure category was scored. Of the five categories of seizures investigated, only focal and generalized tonic extension seizures were observed after allylglycine in the doses tested. Female rats were significantly more susceptible than male rats to allylglycine-induced focal (p less than 0.007) and generalized tonic extension (p less than 0.05) seizures. The results suggest that male-female differences in presynaptic GABA activity may have relevance for sex differences in the occurrence of focal and tonic extension seizures. Differences in the seizure profiles associated with allylglycine and picrotoxin suggests that pre- and postsynaptic antagonism of GABA activity may have different consequences for specific seizure categories and the sex differences associated with those categories.

Allylglycine↗

Congenital complete atrioventricular block--two cases report.

We encountered two cases of congenital complete atrioventricular block out of 23,400 deliveries during the past 3 years. Two-dimensional and M-mode fetal echocardiography revealed complete atrioventricular block without structural abnormality. Anti-Ro (SS-A) antibodies were present in both the mother and infant of these two cases. The ventricular rates of these two infants were 31 and 80 beats/min respectively. Pacemaker implantation was performed for the first infant.

Adult↗

Leiomyosarcoma of the broad ligament--report of two cases.

Leiomyosarcoma of the broad ligament (LBL) is a very rare tumor. Up to 1989, there had been only 7 cases reported in the English literature. During recent 12 years, we have had 15 cases of leiomyosarcoma in our department. Among them, there were two cases of LBL. The others were leiomyosarcoma of the uterine corpus. The first patient was 36 years old. She received total abdominal hysterectomy, bilateral salpingo-oophorectomy and paraaortic lymph node sampling followed by chemotherapy with adriamycin. Intra-abdominal recurrence with hepatic metastasis occurred 18 months after operation and she received palliative radiotherapy. The second patient was 65 years old and received subtotal hysterectomy, bilateral salpingo-oophorectomy, omental biopsy and suprapubic cystostomy followed also by chemotherapy with adriamycin. She received segmental resection of ileum and ileostomy due to intestinal obstruction caused by metastasis 5 months after her initial operation. Both patients were still alive when reported with 33 and 26 months of survival, respectively. The nature and management for LBL are scarcely reported, accumulation of cases and clinical experiences are needed.

Adult↗

Prenatal diagnosis of intracardiac rhabdomyoma: a case report.

We report on a case of intracardiac rhabdomyoma diagnosed prenatally from two-dimensional echocardiograms. The tumor was diagnosed by intrauterine echocardiography at the 38th week of gestation. Autopsy proved that the intracardiac tumor was a rhabdomyoma. Tuberous sclerosis spots in the brain tissue were also found.

Adult↗

Mast cell growth factor (c-kit ligand) enhances cytokine stimulation of proliferation of the human factor-dependent cell line, M07e.

Murine mast cell growth factor (muMGF), a c-kit ligand, has additive to greater-than-additive effects on in vitro colony formation of murine and human myeloid progenitor cells stimulated with erythropoietin, granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin (IL)-3. To confirm direct-acting effects on responding cells, MGF was assessed alone and in combination with other cytokines for effects on the proliferation of the human factor-dependent cell line, M07e. Proliferation was assayed in liquid culture by [3H]thymidine uptake and in semisolid medium by colony formation. Purified recombinant (r) muMGF (25-50 ng/ml) by itself had proliferative activity but less than r human (hu) GM-CSF. In combination with rhuGM-CSF (250 U/ml) or IL-3 (500 U/ml), rmuMGF (25 ng/ml) enhanced [3H]thymidine uptake two- to sevenfold greater than the sum of the effects of each factor alone. Similar enhancement was seen in the number and size of colonies formed. When MGF was used in combination with rhuIL-4 (500-1000 U/ml), rhuIL-6 (5 ng/ml), rhuIL-9 (5-10 U/ml), or rhu interferon gamma (IFN-gamma; 250-500 U/ml) (factors that alone stimulate little proliferation), [3H]thymidine uptake and colony formation were respectively increased 2- to 11- and 3- to 55-fold over the sum of each of the effects of the factors alone. Exposure of 5 x 10(5) cells/ml to 50 ng/ml MGF for 24 h, a time during which synergism is noted with MGF plus either GM-CSF or IL-3, did not change GM-CSF or IL-3 receptor binding affinity or the number of binding sites. Exposure of cells to MGF for 48 h did not alter subsequent GM-CSF- or IL-3-stimulated proliferation. The results suggest that M07e cells will be useful as a model for the analysis of intracellular biochemical mechanisms of the direct-acting proliferative and synergistic effects of MGF.

Animals↗

Human T-lymphotropic virus type I genome in adult T-cell leukemia/lymphoma.

The proviral DNA of human T-lymphotropic virus type I (HTLV-I) was examined in 8 patients with adult T-cell leukemia/lymphoma (ATL/L) by Southern blot analysis. Judging from the number of bands containing viral DNA sequences in tumor cells, one and three copies of proviral genome were detected in 7 and 1 cases, respectively. The proviral genome in 1 case contained variant PstI sites and a single defective provirus which lost 5' LTR, gag and a part of pol genes was found in 2 cases. However, the pX region was detected in both of 2 latter cases by using the polymerase chain reaction. The results indicate that not all tumor cells from ATL/L yield infectious viruses and also support that the product of pX region may contribute to the tumorigenesis of HTLV-I.

Adult↗