Biomedical subjects

J R Chen

Publications and source records attributed to J R Chen.

At least 37 records · Page 2Linked to original sources

PubMed1999

Comparison of the concentrations of pentosidine in the synovial fluid, serum and urine of patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: Pentosidine, an advanced glycation end product (AGE), has recently been observed to be elevated in rheumatoid arthritis (RA). The aim was to elucidate which pentosidine levels, i.e. in serum, synovial fluid or urine, are more related to the disease status of RA. METHODS: We measured levels of pentosidine in serum, synovial fluid or urine in RA compared with osteoarthritis (OA), and examined the relationship between pentosidine and RA disease activity. Subjects were 20 patients with RA and 22 patients with OA. RESULTS: In total RA and OA patients combined, there was a significant correlation between pentosidine in serum, synovial fluid and urine. Pentosidine in serum and synovial fluid was significantly higher in RA than in OA. In RA, there were significant correlations between pentosidine in serum and synovial fluid and C-reactive protein, Lansbury index (LI) and erythrocyte sedimentation rate. CONCLUSIONS: These results demonstrate that pentosidine levels in body fluids correlated with each other, and pentosidine in serum and in synovial fluid is associated with the systemic inflammatory activity of RA. Higher or similar concentrations of pentosidine in serum compared with synovial fluids indicate that the elevated pentosidine levels in serum in RA are not derived from the synovial fluid, but from an increase in the formation of pentosidine in the whole body in RA. Among body fluids, serum pentosidine was the superior indicator for RA disease status.

Adult↗

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

A dynamic local bump system for producing synchrotron radiation with an alternating elliptical polarization.

To facilitate high-sensitivity soft X-ray magnetic circular dichroism experiments, a dynamic local bump system has been developed at the SRRC storage ring. This system was devised to vary dynamically the vertical slope of the electron beam in a bending magnet, producing, in the electron orbit plane, soft X-rays with an alternating elliptical polarization. The local bump was created by using two pairs of vertical correctors located on each side of the bending magnet. The bump strength coefficient was obtained both from calculated estimation and from measured beam-response matrices. Control electronics for proper bump strength settings were designed to incorporate the existing orbit-corrector function. A corresponding graphic user interface was implemented so that the bump amplitude could be easily adjusted. The performance of this system is presented. Disturbance on the stored electron beam orbit was observed while flipping the corrector polarity during EPBM (elliptical polarization from bending magnets) operation. A local feedback loop, developed to eliminate such disturbance on other beamlines, is also described.

Journal Article↗

PubMed1998

Effects of magnets with non-unit magnetic permeability on an elliptically polarizing undulator.

This study employs the three-dimensional magnetostatic code TOSCA to assess numerically the effects of NdFeB magnets with non-unit magnetic permeability on an elliptically polarizing undulator. A reduction of a few percent of the on-axis magnetic field strength is predicted. In addition, a deviation of +/-100 G cm uncompensated dipole steering is predicted in a phase shift of 180 degrees for the elliptically polarizing undulator EPU5.6 (having a period length of 56 mm) at the minimum gap of 18 mm, which is related primarily to the configuration of the device end scheme. Results presented herein demonstrate that implementing an active compensation mechanism is a prerequisite for minimizing the orbit distortion during phase-shift adjustment, particularly for operating such a polarizing undulator in a third-generation machine having a median energy similar to that of the 1.5 GeV storage ring at SRRC.

Journal Article↗

PubMed1998

Spectral properties of the polarizing devices at SRRC.

User requirements at SRRC for high-brilliance synchrotron light in various polarization states will be fulfilled in the near future by the implementation of two types of polarizing devices in the storage ring: the elliptically polarizing undulator (EPU) and the elliptically polarized bending magnet (EPBM). The EPBM provides a broadband polarized spectrum up to the soft X-ray range with rapid alternation of the left and right helicities. The EPU, which has a magnetic period length of 56 mm, generates a high-brilliance harmonic spectral intensity in the range 80-1400 eV with abundant polarization states, including circular ones. The optimal merit flux is evaluated for the operation of these two polarizing devices in the SRRC 1.5 GeV storage ring. The available polarization states are also surveyed.

Journal Article↗

PubMed1998

A synchrotron radiation beam-position monitor at the Taiwan Light Source.

A prototype photon-beam-position monitor has been designed, fabricated and tested at the Taiwan Light Source of the Synchrotron Radiation Research Center. Aluminium was chosen as the material of the blade electrodes due to its low atomic number and high thermal conductivity. The resolution of this photon-beam-position monitor was <+/-1 micro m. The sensitivity of the blade electrode has been measured in situ. Results of measurements for bending-magnet light and undulator light with different gaps are described.

Journal Article↗

PubMed1998

A compact mirror manipulator in the SRRC beamline.

A compact mirror manipulator which has high stiffness and is easily adjustable has been developed for new beamlines at SRRC. It consists of a vertical stem to support the mirror and allows for six-axis precise positioning. The rotation adjustment is designed with a minimum of cross-coupling between adjustments. An independent support is fixed to the ground to reduce vibration from the chamber and the pump. Some performance test results in vacuum and in atmosphere, including vibration, repeatability, long-term drift etc., are described in this paper.

Journal Article↗

PubMed1998

The commissioning of a flexible low-cost multipurpose X-ray beamline at SRRC.

A low-cost multipurpose X-ray beamline has been commissioned at the bending magnet B15 of the Synchrotron Radiation Research Center (SRRC). The beamline is constructed in such a way to accommodate the various needs of small research consortia, from universities or research institutes, whose requirements of a beamline facility are quite diverse while under limited funding support. Flexibility is the special feature of this beamline. It is capable of performing quick test measurements without a prolonged reviewing process. Switching between different techniques, such as white-beam irradiation, EXAFS and X-ray scattering, can be achieved within 1 h. Novel experiments, such as energy-dispersive small-angle scattering experiments and energy-dispersive reflectivity measurements, can also be performed.

Journal Article↗

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↗