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Biomedical subjects

J R Chen

Publications and source records attributed to J R Chen.

At least 55 records · Page 3Linked to original sources

[The investigation of the immunomodulatory effect of san-hwang-sei-sin-tang].

San-Hwang-Sei-Sin-Tang is a famous ancient Kampo. In order to investigate the immunomodulatory effect of this Kampo, we can stimulate lymphocytes with PHA to study the lymphocyte transformation and IL-2 production as indicators of effect. In this study, we found that the extract of San-Hwang-Sei-Sin-Tang at the concentration of 0.1 mg/ml and 1 mg/ml could effectively inhibit the index of lymphocyte transformation. San-Hwang-Sei-Sin-Tang at the concentration of 0.01 mg/ml, 0.1 mg/ml and 1 mg/ml also have the tendency of inhibition of IL-2 production. In the future, San-Hwang-Sei-Sin-Tang may be developed as an effective immunosuppressant.

Dose-Response Relationship, Drug↗

Agonists for endothelial P2 purinoceptors trigger a signalling pathway producing Ca2+ responses in lymphocytes adherent to endothelial cells.

Recirculation of lymphocytes through the body involves their frequent adhesion to endothelial cells but little is known of the signalling pathways between these two cell types. Lymphocytes from patients with chronic lymphocytic leukaemia were loaded with the Ca(2+)-sensitive indicator, fura 2, and allowed to adhere to either glass or monolayers of human umbilical-vein endothelial cells. Addition of ATP or UTP (1-10 microM) to the superfusate produced a transient rise in cytosolic Ca2+ concentration in the lymphocytes adherent to endothelium (24 of 35 cells). In contrast, ATP or UTP (1-10 microM) had no effect on the cytosolic Ca2+ of lymphocytes attached to glass. As the only lymphocyte receptor for ATP (P2Z class) requires higher ATP concentrations ( > 50 microM) for Ca2+ influx and is unresponsive to UTP, the involvement of a lymphocyte P2Z purinoceptor is unlikely. Various agonists including ATP, UTP, 2-methylthioATP, ADP and histamine all stimulated increases in endothelial cytosolic Ca2+ but only ATP and UTP (both agonists for endothelial P2U purinoceptors) triggered Ca2+ transients in adherent lymphocytes. Removal of extracellular Ca2+ did not abolish the ATP-induced rise in cytosolic Ca2+ concentration in lymphocytes adherent to endothelial cells. These findings show that stimulation of endothelial P2U purinoceptors triggers an endothelial-lymphocyte signalling pathway which releases internal Ca2+ in adherent lymphocytes.

Adenosine Triphosphate↗

Induction of Ca2+ signaling and possible exocytosis in endothelial cells by a stable leukocyte-derived factor.

Previous studies have shown that polymorphonuclear leukocytes (PMNs) release a stable factor that inhibits endothelium-dependent relaxation. In the present studies, the effects of the factor on Ca2+ signaling and on ultrastructure of endothelial cells were investigated. In the cultured endothelial cells, the PMN-derived factor induced an increase in [Ca2+]i in a pattern of oscillations. The frequency of the Ca2+ oscillations was less than 3 spikes/10 minutes. Removal of extracellular Ca2+ by perfusion with Ca(2+)-free Krebs' solution abolished the spikes. The results of electron microscopy showed that this factor induced an increase in vesicle formation on the luminal surface of the rat aortic endothelium. The increased vesicle formation may represent exocytosis. The structure of the smooth muscle cells was not changed. In conclusion, the PMN-derived factor induces a Ca2+ influx and In conclusion, the PMN-derived factor induces a Ca2+ influx and possible exocytosis, suggesting that the factor may have other biological functions besides the inhibition of the vascular relaxation.

Animals↗

Potent inhibitory effect of SR 49059, an orally active non-peptide vasopressin VIa receptor antagonist, on human arterial coronary bypass graft.

1. The effect of vasopressin receptor antagonists varies between analogues (peptide, non-peptide) and across species. In this study the effect of the novel non-peptide vasopressin V1a receptor antagonist SR 49059 on human internal mammary arteries was investigated. 2. SR 49059 produced a potent, concentration-dependent, inhibitory effect on vasopressin-induced contraction of human coronary bypass graft internal mammary arteries. Both SR 49059 (1 mumol/l) and a peptide selective V1a antagonist ([d(CH2)5sarcosine7]arginine vasopressin) (1 mumol/l) abolished vasopressin-induced contraction. The non-peptide V1a receptor antagonist OPC-21268 (1 mumol/l) had no effect on vasopressin-induced contraction. 3. The effect of SR 49059 was specific to vascular vasopressin receptors as noradrenaline-induced contraction was not influenced by SR 49059. 4. The results of this study in vitro indicate that the non-peptide SR 49059 is a potent, specific vasopressin V1a receptor antagonist in the human internal mammary artery and suggest that it may be a useful tool for studying the pathophysiological role of vasopressin in man.

Antidiuretic Hormone Receptor Antagonists↗

Various cells release a stable small molecule that inhibits endothelium-dependent relaxation.

Previous studies have shown that neutrophils release a stable factor that inhibits endothelium-dependent relaxation. In the present studies, the effects of supernatants derived from various cells on endothelium-dependent relaxation were studied. Cells were obtained from seven sources: human hematopoietic cells including mononuclear leukocytes (MONO), polymorphonuclear leukocytes (PMNs), and chronic lymphocytic leukemia (CLL) cells; cells of the cardiovascular system including human endothelial cell line ECV304, human smooth muscle cells, and rat myocardial cells; and the tumor cell line HPB. These isolated or cultured cells were incubated for 1 h in Krebs solution to release the factor. The results showed that the supernatants from 10(5) cells/ml of all cells except the tumor cell line HPB produced a potent inhibitory effect on endothelium-dependent relaxation of rat aortic rings in response to acetylcholine and Ca2+ ionophores A23187 and ionomycin but not on endothelium-independent relaxation to nitroprusside and glyceryl trinitrate. When the concentration increased to 10(6) cell/ml, the supernatants from the tumor cell line HPB also slightly but significantly inhibited endothelium-dependent relaxation. The potency order was PMNs = MONO = CLL cells > cardiac cells > smooth muscle cells > the endothelial cell line ECV304 > the tumor cell line HPB. It seems that the hematopoietic cells and the cardiac cells are more active in release of the factor. The effect of this factor was rapid in onset and hard to wash out. A cyclooxygenase inhibitor or a thromboxane A2-prostaglandin H2 receptor antagonist partially but significantly reduced the effect of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

HLA-DRB1 genotyping in patients with rheumatoid arthritis in Taiwan.

OBJECTIVE: To investigate the relation of HLA-DR alleles to the development of rheumatoid arthritis (RA) and the correlations between HLA-DR alleles and clinical manifestations of patients with RA in Taiwan. METHODS: The HLA-DRB1 alleles were studied in 144 patients with RA and 154 healthy controls using polymerase chain reaction/sequence specific oligonucleotide probe methods. The subtypes of HLA-DR4 were detected by cloning sequencing. RESULTS: The prevalence of HLA-DR4 was significantly higher in patients with RA (46.53%) than in healthy controls (25.97%). HLA-DRB1*0405 was more common in patients than in controls (83.58 vs 50%), while the prevalence of DRB1*0403 in patients (4.48%) was significantly lower than in controls (27.5%). There was no significant difference in frequencies of HLA-DR alleles between DRB1*0405 negative patients and DRB1*0.05 negative controls. We also noted a positive correlation in patients between HLA-DR4 and bone erosion, but not HLA-DR4 and age of onset, seropositivity, or extraarticular involvement. There was no significant difference in seropositivity, extraarticular involvement, and bone erosion between homozygous and heterozygous DR4 patients. CONCLUSION: HLA-DRB1*0405 is related to the development of RA in Taiwan, while DRB1*0403 was a negative risk factor. HLA-DR4 was associated with bone erosion in patients.

Alleles↗

Hepatocytic differentiation of cultured rat pancreatic ductal epithelial cells after in vivo implantation.

We have investigated the differentiation potential of propagable cultured rat pancreatic duct epithelial cells after in vivo implantation in isogeneic Fischer-344 rats. Cells genetically labeled with Escherichia coli beta-galactosidase (lacZ) reporter gene were embedded in a mixture of collagen and Matrigel (basement membrane matrix) and implanted either subcutaneously or intraperitoneally. Tissues from the two locations were harvested 4 to 8 weeks later. The great majority of the lacZ-labeled epithelial cells colonizing both sites phenotypically resembled hepatocytes, although they demonstrated different degrees of hepatocytic differentiation. Less than 5% of lacZ-labeled cells formed ductular structures. The hepatocyte-like cells from the subcutaneous implantation site expressed mixed phenotypes of both hepatocyte and ductal cell, including the expression of alpha-fetoprotein, tyrosine amino-transferase, gamma-glutamyl transpeptidase, carbonic anhydrase II, and cytokeratin 19. In contrast, the hepatocyte-like cells colonizing the mesentery showed the phenotype of mature hepatocytes, including an abundant glycogen storage and a lack of alpha-fetoprotein and carbonic anhydrase II expressions. Neither acinar cell nor endocrine differentiation was seen. These findings demonstrate that pancreatic ductal cells can be the progenitor cell for transdifferentiated hepatocytes.

Animals↗

HLA-DPB1 polymorphism in patients with rheumatoid arthritis in Taiwan.

OBJECTIVE: To investigate the role of HLA-DP alleles in the pathogenesis of rheumatoid arthritis (RA). METHODS: HLA-DPB1 alleles were studied in 144 patients with RA and 144 healthy controls using the polymerase chain reaction/sequence specific oligonucleotide probe method. RESULTS: HLA-DPB1*0510 was the the most common allele in patients with RA and healthy controls in Taiwan. There was no significant difference in frequencies of HLA-DPB1 alleles between patients and controls. The HLA-DPB1 alleles were not associated with seropositivity for rheumatoid factor, extraarticular involvement, or bone erosion in patients. There was also no significant difference in frequencies of HLA-DPB1 alleles among DR4-positive and DR4-negative patients and controls. CONCLUSION: There was no significant difference in the prevalences of HLA-DPB1 alleles between Taiwanese patients with RA and healthy controls. HLA-DPB1 alleles were not related to the clinical manifestations of patients with RA in Taiwan.

Alleles↗

Extracellular ATP increases NH4+ permeability in human lymphocytes by opening a P2Z purinoceptor operated ion channel.

The permeability of lymphocytes to NH4+ was examined by measuring intracellular pH using the fluorescent pH-sensitive dye BCECF. Addition of 20 mM NH4Cl produced a rapid phase of alkalinization. This was followed by a slow return to resting pHi due to NH4+ influx. The rate of NH4+ was increased many fold by extracellular ATP and the increment showed features consistent with NH4+ being a permeant for the P2Z purinoceptor operated ion channel. Cytosolic pH measurements showed monomethylammonium+ and dimethylammonium+ were also permeants, but trimethylammonium+ (69 Dalton) was excluded by this channel. Since our previous data showed ethidium+ (314 Dalton) is a permeant it appears that molecular conformation rather than molecular weight determines entry of cationic solutes through the channel.

Adenosine Triphosphate↗

Evaluation of the macrocyclic antibiotic vancomycin as a chiral selector for capillary electrophoresis.

Vancomycin is one of a family of related macrocyclic glycopeptide antibiotics that were discovered by scientists at the Eli Lilly Company in the 1950s. It has been used to treat severe staphylococcal infections, particularly when bacterial resistance to other antibiotics has developed. Vancomycin is a naturally occurring chiral compound and has a number of stereogenic centers. Furthermore, it contains a variety of functionalities that are known to be useful for enantioselective interactions (e.g., hydrogen bonding groups, hydrophobic pockets, aromatic groups, amide linkages, etc.). The physiochemical properties of vancomycin, including its stability in solution, are discussed as they pertain to capillary electrophoresis. Over 100 racemates were resolved including many nonsteroidal antiinflammatory drugs, antineoplastic compounds and N-derivatized amino acids. Many of these compounds had very high resolution factors. Optimization and the effect of different experimental parameters on the enantioselective separations are discussed.

Amino Acid Sequence↗

Autologous neutrophil derived supernatants inhibit endothelium dependent relaxation in human coronary bypass graft.

OBJECTIVE: Spasm of internal mammary artery is a problem during coronary artery bypass grafting. The mechanism is unknown. The aim of this study was to determine whether supernatants derived from neutrophils affected endothelium dependent relaxation of human internal mammary artery. METHODS: The studies involved use of an organ chamber, measurement of cytosolic Ca2+, electron microscopy, and chemical characterisation. RESULTS: Autologous neutrophils and internal mammary artery were obtained from patients undergoing the bypass grafting. Supernatants derived from the neutrophils were used to treat the patients' internal mammary artery rings. The results showed that the supernatants derived from 1 x 10(3)-5 x 10(6) cells.ml-1 neutrophils produced a potent concentration dependent inhibition of the endothelium dependent relaxation to ATP, acetylcholine, and the calcium ionophore A23187, but not the endothelium independent relaxation to sodium nitroprusside. In cultured human endothelial cells, the neutrophil derived supernatants induced an increase in cytosolic calcium ([Ca2+]i), caused calcium oscillations, and desensitised the ATP induced increase in [Ca2+]i. The increased [Ca2+]i resulted from a calcium influx. The supernatants also induced an increase in vesicle formation and possibly exocytosis in the internal mammary artery endothelium. Chemical characterisation showed that the effect of the supernatants was caused by a factor that is stable to heat, extreme pH and protease, is negatively charged and weakly hydrophobic, and has a molecular weight under 500 Dalton. CONCLUSIONS: Autologous neutrophils release a stable non-protein small molecule that disturbs internal mammary artery endothelial function. Since it raises [Ca2+]i and causes possible exocytosis, it may have functions beyond its inhibition of vascular relaxation. This factor could be one of the contributors to internal mammary artery spasm and late atherosclerosis.

Acetylcholine↗

The P2Z-purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP.

1. Extracellular adenosine triphosphate (ATP) is known to open a receptor-operated ion channel (P2Z class) in human lymphocytes which conducts a range of cationic permeants. The activity of a range of different agonists and inhibitors towards the P2Z-purinoceptor was investigated by measuring the agonist-induced influx of Ba2+ into fura-2 loaded lymphocytes. 2. The most potent agonist was 2' & 3'-0-(4-benzoylbenzoyl)-ATP (benzoylbenzoic ATP) which gave 2 fold greater maximum Ba2+ influx and had a 10 fold lower EC50 than for ATP. The rank order of agonist potency in K(+)-media was benzoylbenzoic ATP >> ATP = 2-methylthio ATP = 2-chloro ATP > ATP-gamma-S. ADP, UTP and alpha,beta-methylene ATP were unable to stimulate Ba2+ influx. 3. Extracellular Na+ inhibited the increment of Ba2+ influx induced by all concentrations of ATP, 2-methylthio ATP, 2-chloroATP and ATP-gamma-S. This inhibitory effect of extracellular Na+ is also reflected in the different EC50s for benzoylbenzoic ATP (8 microM in K(+)-media, 18 microM in Na(+)-media) but the maximal response to this agonist was the same in the presence or absence of Na+. 4. Treatment of lymphocytes with 2,3 dialdehyde ATP (oxidized ATP0 at 300 microM for 60 min gave total and irreversible inhibition of ATP-induced Ba2+ influx. 5'-p-Fluorosulphonyl benzoyladenosine (FSBA) also was an irreversible inhibitor but the maximal inhibition achieved was 90%. 5. It is concluded that the P2z-purinoceptor of human lymphocytes has a rank order of agonist potency which clearly distinguishes it from other P2-receptors and that oxidized ATP is a convenient irreversible inhibitor for the P2Z-purinoceptor.

Adenosine Triphosphate↗

Malignant pheochromocytoma associated with Jaccoud's-type arthropathy, Raynaud's phenomenon, positive antinuclear antibody and rheumatoid factor.

We describe a patient with malignant pheochromocytoma who developed Jaccoud's-type arthropathy and Raynaud's phenomenon as initial manifestations of malignant pheochromocytoma. Serologic findings included positive antinuclear antibody (ANA) and rheumatoid factor (RF) was also found in this patient. To our knowledge, this is the first time Jaccoud's-type arthropathy with positive ANA and RF has been reported as rheumatic manifestations of pheochromocytoma.

Adrenal Gland Neoplasms↗

Rheumatoid factor in hepatitis B virus surface antigen positive patients.

Rheumatoid factor (RF) is often found in the sera of patients with nonrheumatic diseases in comparison with normal individuals. We collected 95 healthy HBs antigen positive adults and 98 healthy HBs antigen negative adults. RF was present in 14.74% (14/95) of the HBs antigen positive group while it was present in 3.06% (3/98) of the HBs antigen negative group (p < 0.05). RF was positive in 15.38% (2/13) of the HBe antigen positive patients whereas it was positive in 14.63% (12/82) of the HBe antigen negative patients (p > 0.05). RF was found positive in 16.90% (12/71) of the anti-HBe antibody positive group while it was positive in 8.33% (2/24) of the anti-HBe antibody negative group (p > 0.05). We conclude that the positive rate of RF in HBs antigen positive patients is significantly higher than in that of HBs antigen negative patients. The incidence of RF positivity of the HBe antigen positive group is not higher than that of the HBe antigen negative group. The positive rate of RF in anti-HBe antibody positive group has a tendency to be higher than in that of their negative counterparts though there was no significant difference between them.

Adult↗

Neoplastic transformation of propagable cultured rat pancreatic duct epithelial cells by azaserine and streptozotocin.

The role of duct cells in the histogenesis of pancreatic carcinoma was studied using a propagable cultured pancreatic duct epithelial cell line derived from a Fischer-344 rat. Tumorigenic transformation was induced by treatment with two experimental pancreatic carcinogens, azaserine and streptozotocin, or spontaneously using a 'selective' culture condition. Tumors arising from spontaneously transformed cells were anaplastic carcinomas, while those from streptozotocin-transformed cells were well or moderately differentiated ductal adenocarcinomas. Azaserine-treated cells produced moderately to poorly differentiated adenocarcinomas. Ultrastructural evidence of acinar or endocrine differentiation was absent. The biochemical phenotypes of representative tumor cell lines established from these tumors were studied. As compared to the parental cell line which expressed high activity of carbonic anhydrase (CA) and negligible activity of gamma-glutamyl transpeptidase (GGT), the tumor cell lines displayed variably increased levels of GGT, and a diminution or loss of CA activity. The tumor cell lines also showed heterogeneity in proto-oncogene and growth factor/receptor expression. The transforming growth factor-alpha mRNA expression was increased in all tumor cell lines, especially in those induced by azaserine. In contrast, mRNA expression of epidermal growth factor receptor was markedly down-regulated in all tumor cell lines. All chemically induced tumor cell lines showed marked overexpression of the c-myc and c-Ki-ras mRNAs, whereas the spontaneously transformed tumor cell line showed only a significant overexpression of the c-Ki-ras. Point mutation of this proto-oncogene at codons 12, 13 or 61 was absent. The results show that azaserine and streptozotocin are potent carcinogens in vitro for cultured rat pancreatic duct epithelial cells, and the phenotype of the tumors is modulated by the method or agent used for their transformation.

Animals↗

The effects of Chinese herbs on improving survival and inhibiting anti-ds DNA antibody production in lupus mice.

Systemic lupus erythematosus (SLE) is an important autoimmune disease with multiple organ system involvement. From preliminary studies, we have found that six Chinese herbs: Atractylodes ovata, Anqelica sinensis, Cordyceps sinensis, Liqustrum lucidum, Codonopsis pilosula and Homo sapiens can improve defective in vitro interleukin-2 (IL-2) production in patients with SLE. In order to investigate the in vivo effects of these herbs, we used NZB/NZW F1 mice, a typical lupus animal model used to test these herbs. It was found that C. pilosula, H. sapiens and C. sinensis could prolong the life span of female NZB/NZW F1 mice and inhibited anti-ds DNA production. Although A. sinensis could prolong the life span of experimental mice, it did not inhibit the production of anti-ds DNA antibody. These herbs may have great potential for the management of human SLE in the future.

Animals↗

Inhibition by a stable factor derived from neutrophils of endothelium-dependent relaxation in rat aorta.

Polymorphonuclear leukocytes (PMNs) may play an important role in many pathophysiological states. The effect of a factor derived from PMNs on endothelium-dependent relaxation was studied using rat aortic rings in organ chambers. PMNs were obtained from cardiac surgical patients and healthy volunteers. After incubation in Krebs solution for 3 h, supernatants of PMN suspensions were isolated and used to pretreat the aortic rings for 30 min. The results showed that the supernatants derived from 1 x 10(4) to 5 x 10(6) cells/ml PMNs produced a concentration-dependent inhibition of endothelium-dependent relaxation to acetylcholine but not endothelium-independent relaxation to sodium nitroprusside. The effect could not be prevented by oxygen free radical scavenger superoxide dismutase (150 U/ml), catalase (1,200 U/ml), or mannitol (20 mM) used alone or in combination. Heating the supernatants at 95 degrees C for 30 min did not reduce the inhibitory effect. L-Arginine at 3 x 10(-5) to 3 x 10(-3) M did not significantly reverse the inhibitory effect of the PMN-derived factor. In conclusion, this study reveals that a heat-stable factor derived from human PMNs potently inhibits acetylcholine-induced endothelium-dependent relaxation but not sodium nitroprusside-induced endothelium-independent relaxation in rat aorta. This inhibitory effect is not caused by oxygen free radicals, a limitation of nitric oxide precursor or other unstable factors.

Animals↗

Behçet's disease with inferior vena cava occlusion--a case report.

Behçet's disease is a chronic relapsing inflammatory process affecting mucocutaneous, ocular, intestinal, articular, vascular, urogenital, and neurologic systems. Vascular lesions include superficial thrombophlebitis, large vein thrombosis and arterial aneurysm. The underlying pathologic feature was thought to be vasculitis. We report a case of a 37-year-old male patient suffering from frequent attacks of leg swelling and tenderness. Progressive engorgement of abdominal superficial veins was observed. Venography demonstrated evidence of deep vein thrombosis in both limbs. MRI of the abdomen showed thrombosis of the inferior vena cava with collateral circulation. The above symptoms improved after treatment.

Adult↗