Biomedical subjects

J R Chen

Publications and source records attributed to J R Chen.

At least 19 recordsLinked to original sources

PubMed1999

Miller Fisher syndrome with central involvement: successful treatment with plasmapheresis.

Miller Fisher syndrome is characterized by external ophthalmoplegia, ataxia, and areflexia. Most researchers favor a peripheral origin while others suggest a brainstem inflammatory lesion or a combination of central and peripheral demyelination. We report 2 cases of Miller Fisher syndrome with the typical triad of ataxia, areflexia, and ophthalmoplegia. Strong clinical evidence of central involvement included initial drowsiness, bilateral Babinski sign, and quadriparesis. Evoked potential studies showed prolongation of central conduction time. Plasmapheresis was performed to relieve respiratory failure in Patient 1 and to shorten the duration of nasogastric tube feeding due to severe bulbar palsy in Patient 2. Significant improvement of electrophysiologic parameters was recorded after plasmapheresis. Abnormal evoked potentials, together with clinical evidence of central nervous system abnormalities, support the hypothesis that there is a combination of peripheral and central involvement in Miller Fisher syndrome in our patients. Plasmapheresis is highly effective in relieving the profound neurological deficits of this atypical syndrome.

Adult↗

PubMed1999

Metastable polymorph of etoposide with higher dissolution rate.

Etoposide, an anticancer drug, has low oral bioavailability because of low aqueous solubility, slow dissolution rate, and instability in acidic pH. Our objective was to enhance the aqueous solubility and dissolution rate of etoposide by polymorph formation. Preparation of various polymorphs of etoposide was attempted by crystallizing etoposide from organic solvents. Physicochemical properties of the crystals, namely, crystal habit, thermal behavior with hot-stage microscopy, thermal analysis by differential scanning calorimetry, IR spectrum, and solubility and dissolution rates, were examined. Based on the physicochemical characteristics, a metastable polymorph of etoposide was identified when it was crystallized from isopropanol. The metastable polymorph had an equilibrium solubility and intrinsic dissolution rate of 221 micrograms/ml and 16.3 micrograms/min/cm2, respectively; 1.9 and 1.7 times that of etoposide powder at 25 degrees C, respectively.

2-Propanol↗

PubMed1999

Transendothelial migration of lymphocytes in chronic lymphocytic leukaemia is impaired and involved down-regulation of both L-selectin and CD23.

Chronic lymphocytic leukaemia (B-CLL) is characterized by a progressive accumulation of B lymphocytes in blood and bone marrow and high concentrations of soluble CD23 and L-selectin are found in the serum of these patients. In this study lymphocytes from normal subjects and patients with B-CLL were allowed to undergo transendothelial migration across confluent layers of human umbilical vein endothelial cells. Lymphocytes in B-CLL samples showed an impaired capacity to migrate while the minor proportion of normal T cells was enriched by a mean of 2.5-fold in the transmigrated lymphocytes. In contrast, the ratio of B to T lymphocytes in normal preparations was unchanged in the transmigrated population. The expression of adhesion molecules on B-CLL lymphocytes before and after transendothelial migration was studied by flow cytometry which showed that 71 +/- 5% of L-selectin was lost from the surface of transmigrated lymphocytes. T and B cells from normal subjects also showed a major loss of L-selectin after transmigration. B-CLL lymphocytes and normal B cells expressed CD23 but this molecule was down-regulated following transendothelial migration, whereas the expression of VLA-4, ICAM-1, LFA-1 and CD44 was unchanged. Lymphocytes incubated with oxidized ATP, an irreversible inhibitor of P2Z/P2X7 purinoceptors, retained their capacity for transendothelial migration and showed the same loss of L-selectin as control leukaemic lymphocytes. Our results show that B-CLL lymphocytes have impaired ability for transendothelial migration compared to normal peripheral blood lymphocytes. Moreover, transendothelial migration involves a universal loss of L-selectin and CD23 from lymphocytes which suggests that the high serum levels of soluble L-selectin and CD23 observed in B-CLL may be generated by shedding during the process of transendothelial migration.

B-Lymphocytes↗

PubMed1998

Differential expression of Met/hepatocyte growth factor receptor in subtypes of non-small cell lung cancers.

Hepatocyte growth factor (HGF)/scatter factor (SF) is a multifunctional factor that stimulates epithelial cell motility, invasion and morphogenesis. Its receptor is a transmembrane tyrosine kinase encoded by the Met proto-oncogene. Several studies have suggested a possible role for HGF/Met in tumor development and progression. To investigate the potential roles of Met in human lung cancer biology, we have studied the mRNA and protein expression of Met in normal lung tissue, primary non-small cell lung carcinoma (NSCLC), and NSCLC cell lines. The results indicated a differential pattern of Met expression among various subtypes of NSCLC. The majority of squamous cell carcinoma (SQCC), either in vivo or in vitro, expressed Met mRNA and its protein product at levels much lower than or similar to normal lung tissue or bronchial epithelium. Moreover, SQCC characteristically over-expressed a variant Met mRNA which corresponds to a 5' partially deleted transcript produced by alternative splicing. In contrast, the expression of Met mRNA and its protein product in adenocarcinoma (ADC) and large cell undifferentiated carcinoma were more heterogeneous. Overexpression was demonstrated in approximately 35% and 20% of these subtypes of NSCLC, respectively. Among ADC, intermediate to high levels of Met immunoreactivity correlated with greater degree of tumor differentiation. Furthermore, an accentuation of Met immunoreactivity was often noted in cancer cells at the advancing edge of tumors. These findings support a role for Met in lung cancer cell invasion and differentiation in vivo, but its expression and functions may be modified by the differentiation phenotype of the tumor cells.

Adenocarcinoma↗

PubMed1998

Identification of a novel adhesin-like glycoprotein from Mycoplasma hyopneumoniae.

This study identifies an adhesin-like glycoprotein, which was a 110 kDa protein (P110) under HPLC-GPC assay. This adhesin consisted of one P54 and two P28 subunits. In addition, N-glycosidase F could cleave all N-linked oligosaccharides on the P54 subunit. Experimental results indicated that P110 with native conformations significantly inhibited the adherence of biotin-labeled porcine tracheal epithelial cell extracts to the intact M. hyopneumoniae cells (p < 0.01). Furthermore, the biotin-labeled porcine tracheal epithelial cell extracts specifically bound to P54 and P28 subunits. This binding could be competitively inhibited by unlabeled porcine tracheal epithelial extracts and SPF porcine antisera against Mycoplasma hyopneumoniae. Both P54 and P28 subunits were constitutively expressed in different strains of M. hyopneumoniae. Their production was negligibly changed at various passages during in vitro cultivation. The significant role of this adhesin-like glycoprotein in the pathogenesis of swine pneumonia is under study.

Adhesins, Bacterial↗

PubMed1998

Paracrine effects of hepatocyte growth factor/scatter factor on non-small-cell lung carcinoma cell lines.

We have studied the mitogenic, motogenic and morphogenic effects of hepatocyte growth factor (HGF), also known as scatter factor (SF), on 15 non-small-cell lung carcinoma (NSCLC) cell lines that have had their ras genotype determined. HGF/SF stimulated proliferation in only three cell lines and exerted no mitogenic activity on six lines. The growth of the remaining six lines was inhibited. The mitogenic effects were not related to the ras genotype of these cell lines, but the inhibitory effect was more commonly observed in cell lines with relatively high levels of Met/HGF receptor (HGFR) expression. HGF/SF induced or enhanced both scatter activity on monolayer culture and single-cell invasion in collagen gels in approximately half of these cell lines. Although the ras genotype of tumour cells did not influence the HGF/SF-induced motogenic activity, cell lines with the mutant ras genotype more commonly demonstrated a spontaneous motogenic activity than those with the wild-type ras genotype. When tumour cells were grown in collagen gels, HGF/SF induced irregular branching extensions of cell aggregates formed by five out of eight adenocarcinoma cell lines, but significant lumen morphogenesis was distinctly absent. The presence of autocrine HGF/SF loop in these tumour cell lines did not influence their spontaneous or HGF/SF-induced mitogenic, motogenic or morphogenic activities. Overall, our data suggest that stimulation of cell motility, rather than proliferation or differentiation, is the predominant paracrine effect of HGF/SF on NSCLC cells in vitro.

Carcinoma, Non-Small-Cell Lung↗

PubMed1998

Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship with disease activity in rheumatoid arthritis.

OBJECTIVE: Pentosidine is an advanced glycation endproduct formed by glycosylation and oxidation. Our aim was to develop a means to measure pentosidine in synovial fluid (SF), and to compare its concentration in SF in patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and to investigate the relationship between its concentration in SF and the disease activity of RA. METHODS: SF was collected from knee joints in 31 patients with RA and 40 with OA, who had hydrarthrosis. One patient with RA and 7 with OA who had the complication of diabetes mellitus or chronic renal failure made up the DM/CRF group, and the remaining patients made up the RA group (n = 30) and the OA group (n = 33). Pentosidine was measured by the direct HPLC method with column switching after hydrolysis of SF. RESULTS: Pentosidine was detected in all SF and was greater in RA (83.9 +/- 46.0 nmol/l, mean +/- SD) than in OA (40.1 +/- 19.6 nmol/l). Three DM/CRF patients undergoing hemodialysis had markedly high pentosidine levels (482.5 +/- 280.8 nmol/l). There was a significant correlation between pentosidine and C-reactive protein (CRP), erythrocyte sedimentation rate, and Lansbury Index (p < 0.01). Patients with RA were divided into high and low activity groups according to the CRP and Lansbury Index. Pentosidine was significantly higher in the high activity group (CRP > or = 2.0 mg/dl and Lansbury Index > or = 50%) than in the low activity group (CRP < 2.0 and/or Lansbury Index < 50) (100.9 +/- 42.8 vs 58.5 +/- 39.6 nmol/; p = 0.0013). CONCLUSION: Pentosidine in synovial fluid was higher in RA than in OA. Pentosidine levels in SF were related to the disease activity in RA.

Adult↗

PubMed1997

Serum liver function profiles in coking workers.

Coking workers are regularly exposed to coke oven emissions (COE), which consist mainly of polycyclic aromatic hydrocarbons and volatile organic compounds. In a previous cross-sectional study, we found that coking and by-product workers with heavy exposure to COE in the older of two coke operation areas in Taiwan had higher serum activities of hepatic aminotransferase than the controls. In this study, we further examine the relationship of exposure to COE with liver function profiles in coking workers. Liver function profiles included serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL). The exposed group included 88 workers working 3 months or more in the older coke oven plant. Fifty-nine referents, not visiting the coke operation areas in the last 3 months, came from the administrative area in the same company. Each participant wore a personal monitor that was used to measure benzene soluble fraction (BSF) of total particulates, as a surrogate of COE, for 3 consecutive days between August 1995 and February 1996. Serum liver function profiles, hepatitis B surface antigens, and anti-hepatitis C antibodies were examined in the morning following the exposure measurements. Exposure levels were categorized by exposure situations (high, medium, low) among coking workers. The high exposure group (n = 23) worked topside of the oven. The medium exposure group (n = 44) worked at the sideoven for more than 4 hr/day, whereas the low exposure group (n = 21) worked at the sideoven for less than 4 hr/day and mostly remained in the control rooms. The low exposure group was used as an internal comparison group. The median BSF concentrations for various exposure situations were as follows, high exposure group: 372 micrograms/m3, medium exposure group: 61 micrograms/m3, low exposure group: 49 micrograms/m3, and referents: 10 micrograms/m3. The coking workers (n = 88) did not significantly differ from the referents (n = 59) in any of the liver function profiles. Excluding the referents, workers in the high exposure group had a mean AST level that was 31% higher (95% confidence interval (CI) = 9-57%) and a mean ALT level that was 46% higher (95% CI = 7-98%) than those in the low exposure group after adjusting for appropriate confounders in multivariate models. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/L or ALT > 39 IU/L) was more common in the high exposure group than in the low exposure group (adjusted odds ratio = 4.4; 95% CI = 0.9-22.6). However, these associations were not found in GGT, ALP, or BIL. After controlling for the possible effects of nonoccupational factors on serum activity of AST and ALT, we conclude that increased AST and ALT levels among topside coking workers may be caused by heavy inhalation exposure to COE. Additionally, the adverse hepatic effect seems to be caused by a mixture of hazards, rather than a unique identifiable chemical.

Adult↗

PubMed1997

Direct vasodilator effect of milrinone, an inotropic drug, on arterial coronary bypass grafts. FANZCA .

Milrinone is an inotropic drug with vasodilator activity that has been shown to be useful in increasing cardiac output and decreasing wedge pressure. Despite these advantages, it is unknown whether this drug can be used for the treatment of perioperative spasm of coronary bypass grafts. This study was undertaken to investigate the in vitro vascular effect of milrinone on internal thoracic arteries obtained from patients undergoing coronary artery bypass grafting. The results showed that milrinone produced a potent, concentration-dependent, preventive effect on the norepinephrine-induced contraction of internal thoracic arteries, as well as reversing contraction of internal thoracic arteries by receptor-dependent agents, including the thromboxane A2 mimetic U46619, the vasoconstrictor peptide endothelin-1, and the alpha1-adrenal receptor agonist phenylephrine. The relaxing effect of milrinone was weaker, however, on internal thoracic arteries contracted with 25 mmol/L potassium chloride. Comparison of milrinone with other vasodilators, including papaverine, nitroprusside, and glyceryl trinitrate, showed milrinone to be more potent than papaverine but less potent than nitroprusside and glyceryl trinitrate. The inhibitory effect of milrinone on internal thoracic artery contraction appeared as a reduction in contractile force, not as an increase in the values of concentrations of the agonists causing 50% maximal contraction, which indicates that milrinone exerts its vasodilator effect directly on the smooth muscles, not on the membrane receptors. The results also showed no significant difference in relaxing effect between internal thoracic artery rings with and without endothelium. In conclusion, this study provides experimental evidence that milrinone is a potent, endothelium-independent, direct vasodilator of the human internal thoracic artery and provides the scientific rationale for a future clinical trial with this drug for the perioperative treatment of internal thoracic artery spasm in cardiac surgical patients.

Coronary Artery Bypass↗

PubMed1997

Membrane properties and inhibitory connections of normal and upper cervically axotomized rubrospinal neurons in the rat.

Membrane properties and inhibitory synaptic connections of normal and axotomized rat rubrospinal neurons were examined using a coronal slice preparation. Rubrospinal neurons were axotomized at the C2 vertebral level in vivo. Retrograde labelling in vivo and intracellular biocytin injection following recording were combined to identify recorded axotomized rubrospinal neurons. Their input resistances decreased three and four days and became higher than normal four and 10 weeks following lesioning which coincided with a sequential increase and decrease of their soma area. On the other hand, although their membrane time-constant was reduced three and four days following lesioning, it returned to normal value four and 10 weeks following axotomy. Other than these, their membrane current-voltage relationship including an inward rectification in the hyperpolarizing direction was not altered. Normal rubrospinal neurons generated very fast spikes which were not affected by axotomy. Both normal and axotomized cells generated trains of repetitive spikes with a fast spike frequency adaptation at the beginning upon suprathreshold current injection. However, the slope of the steady-state spike frequency and applied current relationship was increased four and 10 weeks following axotomy which also showed an increased steady-state spike frequency in response to high-amplitude current injection. Synaptically, the amplitude and duration of the monosynaptic inhibitory potential evoked from nearby reticular formation were reduced following axotomy. In addition, fewer rubrospinal neurons were found to receive this inhibition 10 weeks following axotomy. Thus, our results show that spinal axotomy induces a time-dependent modification of the membrane properties and spike generating behaviour of rubrospinal neurons which probably represents an initial decrease and a later increase of their excitability. This is accompanied by a persistent decrease of synaptic inhibition which is expected to affect structures that remained innervated by the undamaged axon collaterals of these spinally axotomized neurons.

Animals↗

PubMed1997

Associations between carotid atherosclerosis and high factor VIII activity, dyslipidemia, and hypertension.

BACKGROUND AND PURPOSE: A subsample of 147 Chinese subjects from a population-based study of cardiovascular diseases (Cardiovascular Disease Risk Factor Two-Township Study) participated in an ancillary study on extracranial carotid color duplex ultrasonography that aimed to assess the relations of coagulation factors to stroke and carotid atherosclerosis. METHODS: Logistic models were used to study the associations between cardiovascular disease risk factors and stroke/carotid atherosclerosis, controlling for the effects of age and sex. RESULTS: Stroke was significantly associated with hypertension and high values of plasma glucose but not with fibrinogen, factor VIIc, or factor VIIIc. Carotid plaques identified in this study were mostly mild and moderate. The presence of these mild and moderate carotid plaques was significantly associated with high values of factor VIII activity, hypercholesterolemia, hypertriglyceridemia, and hypertension. The highest tertile of factor VIIIc (> 1.53) was associated with an odds ratio of 3.35 for carotid atherosclerosis when compared with the lowest tertile (< 1.20). A multiple logistic regression including all significant risk factors showed that the degree of association between factor VIIIc and atherosclerosis was attenuated to an odds ratio of 2.65 (P = .061). CONCLUSIONS: In the present study, the roles of hypertension, hypercholesterolemia, and hypertriglyceridemia have been implicated in the pathogenesis of carotid atherosclerosis, and roles for hypertension and hyperglycemia in stroke were indicated. A positive association between factor VIIIc and carotid atherosclerosis in this Chinese population was found. Whether this association is independent of the effect of other cardiovascular risk factors awaits further study.

Adult↗

PubMed1996

Transduction mechanisms of P2Z purinoceptors.

The ability of extracellular ATP to increase the cation permeability of a variety of fresh and cultured cells has been known for decades, but evidence of a separate class of P2 purinoceptor, termed P2Z, which mediates this effect has only recently been obtained. Several features of the P2Z purinoceptor clearly distinguish it from other P2 purinoceptors and show that it is a ligand-gated ion channel. P2Z purinoceptors are highly selective for the ATP4- species and addition of Mg2+ in excess over ATP closes the channel. The most potent agonist is 3'-O-(4-benzoyl)benzoyl ATP which has a 10-fold lower EC50 than ATP. Ca2+ is the preferred permeant for the P2Z ion channel although it will pass ions up to the size of ethidium(+) (314 Da) in lymphocytes or fura-2 (813 Da) in macrophages. The inhibitors of the P2Z purinoceptor or its associated ion channel include suramin, amiloride analogues, high extracellular Na+ concentrations and 2',3'-dialdehyde ATP (oxidized ATP), which blocks irreversibly. Occupancy of P2Z purinoceptors stimulates a phospholipase D activity, which may be involved in membrane remodelling. Moreover, extracellular ATP causes loss of the glycosylated adhesion molecule L-selection from the surfaces of human lymphocytes by enzymic cleavage, suggesting a possible role for P2Z purinoceptors in intercellular interactions.

Adenosine Triphosphate↗

PubMed1996

Unique response of human arteries to endothelin B receptor agonist and antagonist.

1. The role of the ET(B) receptor in human arteries has not been well studied because of the lack of specific ET(B) receptor antagonists. In the present studies the specific ET(B) receptor antagonist BQ-788 and the specific ET(B) agonist IRL-1620 were used to characterize the function of the ET(B) receptor in human radial arteries and internal mammary arteries. 2. The results showed that the ET(B) antagonist BQ-788 significantly inhibited endothelin-1-induced contraction in internal mammary arteries, but not in radial arteries. In internal mammary arteries, BQ-788 at a concentration of 10 micromol/l shifted the endothelin-1-induced concentration-dependent curve to the right by one order. By comparison, the ET(A) receptor antagonist BQ-610 at 1 micromol/l produced a much more potent inhibitory effect (three-order shifting) on endothelin-1-induced contraction in internal mammary arteries, and also potently inhibited the contraction in radial arteries. 3. The ET(B) agonist IRL-1620 caused a contraction in internal mammary arteries, but not in radial arteries, although the response of radial arteries to endothelin-1 was very strong. The contraction induced by IRL-1620 was weaker than that induced by endothelin-1; however, the maximal contraction to IRL-1620 was obtained at 3 nmol/l, which was lower than that with endothelin-1 (maximal contraction at 10 nmol/l). 4. In internal mammary arteries the contraction to endothelin-1 and IRL-1620 gradually changed to relaxation with high concentrations of endothelin-1 (from 30 nmol/l) and IRL-1620 (from 3 nmol/l), whereas it did not in radial arteries; suggesting that the ETB receptor on human arterial smooth muscle cells may mediate contraction at low agonist concentrations and relaxation at high agonist concentrations. 5. The ET(B) agonist IRL-1620, endothelin-1 and endothelin-3 did not cause endothelium-dependent relaxation in either precontracted radial arteries or internal mammary arteries, although endothelium-dependent relaxation was fully induced by acetylcholine in these two arterial preparations. 6. In conclusion, the present studies demonstrate that the responses of internal mammary arteries and radial arteries to an ET(B) antagonist and an ET(B) agonist are significantly different from those of animal vascular vessels, and also from each other. The ET(B) receptor may play only a minor role in endothelium-dependent relaxation of these human arteries. Endothelin-1-induced contraction is mediated by both the ET(A) (major) and the ET(B) (minor) receptors in internal mammary arteries, but only by the ET(A) receptor in radial arteries. These studies may help to determine therapeutic strategy.

Aged↗

PubMed1996

[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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗