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Biomedical subjects

K C Chang

Publications and source records attributed to K C Chang.

At least 91 records · Page 5Linked to original sources
PubMed1998

Hypertensive effects of methoxamine on arterial mechanics in rats: analysis based on exponentially tapered T-tube model.

Methoxamine, a specific alpha1-selective adrenoceptor agonist, has proven to be useful in the treatment of hypotension, especially hypotension due to failure of the sympathetic nervous system. This study is to explore the vascular dynamic response to methoxamine in Wistar-Kyoto rats, based on the exponentially tapered T-tube model. The pulsatile aortic pressure and flow signals before and after the administration of methoxamine (0.025 mg/kg) were measured by a high-fidelity pressure sensor and electromagnetic flow probe, respectively. Hemodynamic parameters, such as aortic characteristic impedance, wave transit time, and arterial load compliance, were inferred from the aortic pressure and flow signals to describe the pulsatile nature of blood flow in the vasculature. The hypertensive effects of methoxamine on the static components of ventricular afterload were characterized by (1) little change in cardiac output, (2) a decrease in heart rate and (3) an increase in aortic pressure and total peripheral resistance. As for the pulsatile components of ventricular afterload, no significant changes in aortic characteristic impedance and wave transit time were observed, suggesting that the distensibility of the aorta was not altered in rats after the administration of methoxamine. In contrast, there was a significant drop in arterial load compliance mainly due to the elevated arterial blood pressure in methoxamine-treated rats. In conclusion, methoxamine at the dose of 0.025 mg/kg has a greater effect on peripheral resistance vessels than on Winkessel vessels in the rat systemic circulation.

Adrenergic alpha-Agonists↗
PubMed1998

Differentiation of BCG-induced lymphadenitis from tuberculosis in lymph node biopsy specimens by molecular analyses of pncA and oxyR.

Without culture, differentiation of bacille Calmette-Guérin-induced lymphadenitis (BCG-LA) from tuberculosis (TB) is sometimes difficult by histology, but is important because of different treatment schemes. The purpose of this study was to investigate the feasibility of differentiating BCG-LA from TB in lymph nodes (LNs) by molecular analyses of two recently identified genes, pncA and oxyR. In both genes, a single tuberculosis difference exists between Mycobacterium bovis and M. tuberculosis. M tuberculosis complex (MTC) DNA was first detected in nine of ten formalin-fixed, paraffin-embedded LNs from patients aged under 20 years with suspected mycobacterial infections, using polymerase chain reaction (PCR) for IS6110, an insertion sequence specific for MTC species. PCR, together with direct DNA sequencing and PCR-restriction fragment length polymorphism (RFLP) assay, was then performed to identify polymorphic nucleotide in pncA and oxyR, respectively. For comparison, 37 adult cases of tuberculous lymphadenitis were also analysed by PCR-single strand conformation polymorphism (SSCP) assay for pncA and by PCR-RFLP for oxyR. The results revealed that five of the nine IS6110-positive child cases had a G residue at nucleotide 169 in pncA, and also had a three-band pattern after digesting the amplified oxyR segment with AluI, suggesting BCG-LA. The remaining four child cases, as well as all adult cases with detectable IS6110, showed no motility shift in pncA PCR-SSCP and had the same one-band pattern as M. tuberculosis in oxyR PCR-RFLP, suggesting TB lymphadenitis. The data from molecular analyses showed a good correlation with the vaccination history and clinicopathological findings, except for one case. This study indicates that molecular assay of either oxyR or pncA could be a rapid and useful tool to distinguish BCG-LA from TB.

Adolescent↗
PubMed1998

Post-infarction heart failure in the rat is associated with distinct alterations in cardiac myocyte molecular phenotype.

The myocardial molecular and cellular responses to hemodynamic and other hypertrophic stimuli have been characterized extensively, but less is known of the alterations in gene expression during the evolution of heart failure following myocardial infarction, and specifically those affecting the cardiac myocytes. Therefore, the present study was undertaken to test the hypothesis that post-infarction heart failure and remodeling in the rat is associated with a distinct myocyte molecular phenotype. To address this question, hemodynamic measurements were performed in vivo; and myocytes isolated from the non-infarcted myocardium 1 day, 1 week, and 6 weeks post-coronary artery ligation in post-infarct rats and sham controls. Myocyte size, mRNA levels for immediate early genes, contractile proteins, and sarcoplasmic reticulum Ca2+-ATPase (SERCA) and phospholamban were assayed by Northern analyses, and SERCA and phospholamban proteins were examined by Western blotting. Hemodynamic evidence of heart failure was present at all post-infarct time points. Myocyte size was increased significantly at 6 weeks. c-myc expression was increased at 1 day and 1 week in the infarcted rats, but returned to baseline by 6 weeks. Atrial natriuretic peptide and VEGF mRNAs were elevated at 1 and 6 weeks. Both beta-myosin heavy chain and skeletal alpha-actin expression were increased at all post-MI time points. In contrast, neither changes in the expression of the calcium-handling proteins (SERCA and phospholamban) were not observed, nor was there a change in TGFbeta1 or TGFbeta3. These results demonstrate that in rats with post-MI heart failure, there was an immediate induction of the fetal/embryonic transcriptional gene program which preceded myocyte hypertrophy and appeared to persist longer than in pressure-overload models. In further contrast to pressure-overload, expression of sarcoplasmic reticulum Ca2+-ATPase and phospholamban, was not altered despite a comparable degree of cellular hypertrophy and more severe hemodynamic decompensation. These findings suggest that there may be important differences in the regulatory mechanisms underlying these two forms of myocardial hypertrophy and heart failure.

Actins↗
PubMed1998

Comparison of relaxations evoked by photoactivation of NO-containing compounds and nitrergic nerve stimulation in 5-hydroxytryptamine- and potassium-contracted rat gastric fundus.

1. The aim of the present study was to further investigate our earlier proposal of liberation of nitric oxide (NO) by photoactivation of molecules containing NO or NO2, which in turn relaxes gastric smooth muscle, and to determine whether presynaptic- and/or postsynaptic NO-mediated relaxation is affected differently by the degree of membrane depolarization in rat gastric fundus smooth muscle. 2. During contraction of rat gastric fundus with 5-hydroxytryptamine (5-HT, 10 microM), low (K+, 25 mM) and high potassium (K+, 65.4 mM), relaxation responses to nitrergic nerve stimulation, photo-activation of caged NO compounds (streptozotocin [STZ], N omega-nitro-L-arginine-methylacetate [L-NAME], N omega-nitro-D-arginine-methylacetate [D-NAME]), and sodium nitroprusside (SNP) were compared. 3. Nitrergic nerve (presynaptic) stimulation and photoactivation (postsynaptic) of all caged NO compounds produced rapid, transient and reversible relaxation of 5-HT and low-K(+)-contracted tissues. However, when contractions were induced by high K+, the relaxation induced by nerve stimulation was abolished, whereas relaxations induced by photoactivated NO compounds were significantly (P < 0.01) reduced. 4. The relaxation induced by sodium nitroprusside (SNP), but not papaverine, was also diminished in high-K(+)-contracted tissues. The magnitude of photoactivated NO-induced relaxation was related to the amount of NO release, light intensity and concentration of compounds. 5. The evidence that photoactivated NO-induced relaxation is mediated by cGMP comes from the observation that zaprinast, but not forskolin, potentiated the relaxation. 6. It is concluded that rat gastric smooth muscle relaxes to photoactivation of NO or NO2-carrying molecules via NO, and it appears that degree of membrane depolarization may be a critical factor in dissociating the response to presynaptic- and postsynaptic NO-mediated relaxation in this muscle.

Animals↗
PubMed1998

Chronic alcohol-induced changes in cardiac contractility are not due to changes in the cytosolic Ca2+ transient.

Long-standing heavy alcohol consumption acts as a chronic stress on the heart. It is thought that alcohol-induced changes of contractility are due to altered Ca2+ handling, but no measurements of cytosolic Ca2+ ([Ca2+]c) after chronic alcohol exposure have been made. Therefore experiments were performed to determine whether alcohol-induced changes in contractility are due to altered Ca2+ handling by measuring [Ca2+]c (indo 1) in hearts from rats drinking 36% ethanol for 7 mo and age-matched controls. Peak left ventricular pressure was depressed (-16%), whereas rates of contraction (12%) and relaxation (14-20%) were faster in alcohol-exposed hearts. Systolic [Ca2+]c (808 +/- 45 vs. 813 +/- 45 nM), diastolic [Ca2+]c (195 +/- 11 vs. 193 +/- 10 nM), and rates of [Ca2+]c rise and decline were the same in alcohol-exposed and control hearts. Protein levels of Ca2+-handling proteins, sarcoplasmic reticulum Ca2+-ATPase and phospholamban, were the same in myocytes isolated from alcohol-exposed and control hearts (SDS-polyacrylamide gel). These data suggest that chronic alcohol-induced contractile changes are not due to altered Ca2+ handling but may be due to changes at the level of the myofilament. As a first step in elucidating the mechanism(s) of alcohol-induced changes at the myofilament, we assessed myosin heavy chain (MHC) isoform content (SDS-polyacrylamide gel). alpha-MHC was decreased relative to beta-MHC (a/a + b = 0.55 +/- 0.03 vs. 0.66 +/- 0.02; P < 0.02) in alcohol-exposed hearts, which cannot account for the observed alcohol-induced contractile changes. In conclusion, changes of myocardial contractility due to chronic alcohol exposure do not result from altered Ca2+ handling but from changes at the level of the myofilament that do not involve MHC isoform shifts.

Alcohol Drinking↗
PubMed1998

Role for heparin-binding growth factors in glucose-induced vascular dysfunction.

Vascular hyperpermeability and excessive neovascularization are hallmarks of early and late vascular endothelial cell dysfunction induced by diabetes. Vascular endothelial growth factor (VEGF) appears to be an important mediator for these early and late vascular changes. We reported previously, using skin chambers mounted on backs of SD rats, that neutralizing antibodies directed against VEGF blocked vascular permeability and blood flow changes induced by elevated tissue glucose and sorbitol levels in a dosage-dependent manner. We report in this study, using the same skin chamber model and neutralizing antibodies directed against basic fibroblast growth factor (FGF-2), that another member of the heparin-binding growth factor family also mediates glucose- and sorbitol-induced vascular permeability and blood flow increases. In addition, we show that 1) TBC1635, a novel heparin-binding growth factor antagonist, blocks the vascular hyperpermeability and blood flow increases induced by elevated tissue levels of glucose and sorbitol and by topical application of VEGF and FGF-2 to granulation tissue in skin chambers, and 2) suramin, a commercially available growth factor antagonist, blocks glucose-induced vascular dysfunction. These results suggest an early role for heparin-binding growth factors in the vascular dysfunction caused by excessive glucose metabolism, possibly via the sorbitol pathway.

Animals↗
PubMed1998

Penicillium marneffei infection and solitary pulmonary nodule.

We report on a patient infected with human immunodeficiency virus who presented with fever, a solitary pulmonary nodule, and cervical lymphadenopathy. The diagnosis of Penicillium marneffei infection was made from an excisional lymph node biopsy and a sputum culture. The microbiology, pathology, diagnosis, and treatment of the case are discussed. A high level of clinical suspicion is necessary for making an early diagnosis and improving the outcome of infection.

Journal Article↗
PubMed1998

Once-daily nifedipine sustained release (nifelan) on forearm vascular resistance and regression of left ventricular hypertrophy in patients with mild to moderate essential hypertension.

BACKGROUND: Nifelan, a sustained-release formulation of nifedipine, is a new antihypertensive agent. However, its effect on peripheral vascular resistance and left ventricular mass is still controversial. METHODS: We evaluated the antihypertensive efficacy and safety of nifelan in 20 patients with mild to moderate essential hypertension. After 2 weeks of a placebo-qualifying phase, the eligible patients were entered into an 8-week active treatment period in which nifelan was given 10-40 mg once-daily with gradual titration. RESULTS: Seventeen patients (8 men, 9 women; age range 43-72 years, mean 52 years) completed the entire study. The mean sitting systolic and diastolic blood pressures were significantly reduced (p < 0.0001) by 13.8 mmHg and 9.6 mmHg, respectively, with a mean nifelan dose of 27.1 +/- 2.7 mg per day, while the heart rate remained unchanged (75.9 +/- 1.3 vs. 73.6 +/- 0.9 beats per minute, p = NS). Four patients (20%) reported side effects necessitating termination of nifelan treatment in 2 patients because of intolerance. One patient was found to be poorly compliant and withdrew prematurely from the study for unknown reasons without complaints of adverse effects. Echocardiographic left ventricular mass index was significantly reduced from 104.2 +/- 4.6 g/m2 to 96.6 +/- 5.2 g/m2 (p < 0.05), and the left ventricular diastolic function evaluated by E/A ratio showed a trend toward improvement from 0.97 +/- 0.06 to 1.10 +/- 0.07 (p = 0.06). Both forearm hemodynamic parameters showed favorable changes from baseline to the end of the study (forearm blood flow, 3.39 +/- 0.28 vs. 4.04 +/- 0.31 ml/100 ml/min, p < 0.05; forearm vascular resistance, 37.75 +/- 4.95 vs. 28.73 +/- 3.34 mmHg/ml/100 ml/min, p < 0.05). The lipid profiles followed trends toward favorable changes after treatment (high density lipoprotein, 51.8 +/- 3.0 vs. 54.4 +/- 3.3 mg/dl, p = NS; low density lipoprotein, 146.1 +/- 8.8 vs. 139.9 +/- 10.6 mg/dl, p = NS). Hematological and biochemical parameters did not change at the end of treatment. CONCLUSION: Once-daily nifelan as monotherapy was safe and effective in Chinese patients with mild to moderate essential hypertension. Regression of left ventricular mass and reversal of unfavorable forearm hemodynamics were observed in these patients after short-term therapy.

Adult↗
PubMed1998

First branchial cleft anomalies: report of 12 cases.

First branchial cleft anomalies account for only 1-8% of all branchial anomalies. Several classification systems have been proposed to aid in the diagnosis of these defects. We present a series of 12 patients with first branchial cleft anomalies classified according to anatomic criteria. The preferred treatment is complete excision. For patients with acutely inflamed masses, surgery should be performed only after resolution of the infection has been achieved with adequate drainage in combination with antibiotic therapy.

Adolescent↗
PubMed1997

Single-beat estimation of the ventricular pumping mechanics in terms of the systolic elastance and resistance.

An elastance-resistance model has long been used to assess the systolic mechanical behavior of the ventricular pump under an in situ, open-chest experiment. However, there is difficulty in the clinical application of such a model because of the required isovolumetric signal that is obtained by occluding the ascending aorta in diastole. In this study, we determine the characteristics of an elastance-resistance model in the absence of isovolumeric measurement to quantify the physical properties of the left ventricle. A high-fidelity multisensor catheter was used to record the left ventricular pressure and ascending aortic flow in nine anesthetized, closed-chest dogs. The isovolumetric pressure was estimated from the instantaneous pressure of an ejecting contraction by a curve-fitting technique. Thus, the parameters in the characterization of systolic pumping mechanics could be inferred by the use of fitting this elastance-resistance model. The results showed that the maximal systolic elastance was 7.3 +/- 2.8 mmHg and theoretical maximum flow was 494 +/- 194 ml s-1. These data were compatible with other reports in the literature. Moreover, in every dog studied the maximal systolic elastance was smaller than the end-systolic elastance which was determined by using the end-systolic pressure-volume relation. We suggested that an elastance-resistance model with the estimated isovolumetric pressure has the potential to measure the intrinsic systolic mechanics of the left ventricle in a closed-chest cardiovascular system.

Animals↗
PubMed1997

Thyroid hormone improves function and Ca2+ handling in pressure overload hypertrophy. Association with increased sarcoplasmic reticulum Ca2+-ATPase and alpha-myosin heavy chain in rat hearts.

We asked whether thyroid hormone (T4) would improve heart function in left ventricular hypertrophy (LVH) induced by pressure overload (aortic banding). After banding for 10-22 wk, rats were treated with T4 or saline for 10-14 d. Isovolumic LV pressure and cytosolic [Ca2+] (indo-1) were assessed in perfused hearts. Sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban, and alpha- and beta-myosin heavy chain (MHC) proteins were assayed in homogenates of myocytes isolated from the same hearts. Of 14 banded hearts treated with saline, 8 had compensated LVH with normal function (LVHcomp), whereas 6 had abnormal contraction, relaxation, and calcium handling (LVHdecomp). In contrast, banded animals treated with T4 had no myocardial dysfunction; these hearts had increased contractility, and faster relaxation and cytosolic [Ca2+] decline compared with LVHcomp and LVHdecomp. Myocytes from banded hearts treated with T4 were hypertrophied but had increased concentrations of alpha-MHC and SERCA proteins, similar to physiological hypertrophy induced by exercise. Thus thyroid hormone improves LV function and calcium handling in pressure overload hypertrophy, and these beneficial effects are related to changes in myocyte gene expression. Induction of physiological hypertrophy by thyroid hormone-like signaling might be a therapeutic strategy for treating cardiac dysfunction in pathological hypertrophy and heart failure.

Animals↗
PubMed1997

Isolation of a genetic locus associated with metronidazole resistance in Helicobacter pylori.

We examined the molecular mechanism of metronidazole resistance by constructing a lambda-Zap II phagemid expression library with genomic DNA from a metronidazole-resistance strain of Helicobacter pylori. Twenty-two clones were found to have elevated MTZ resistances in XLOLR strain of E. coli. Phagemids belonging to the twenty two clones were extracted and then retransformed into the XLOLR strain of E. coli. After MTZ selection, five clones could confer metronidazole resistance consistently. According to Southern hybridization and DNA sequencing, the five clones contained a same locus, recA. In addition, transforming the five clones into BL21 strain of E. coli produced a higher resistance to MTZ. Interestingly, electroporation of one of the five phagemid clones into two MTZ sensitive H. pylori yielded MTZ resistant strains. Comparing amino acid sequence in MTZ resistant with sensitive isolates revealed two point mutations at this locus. Above results suggest that mutation in recA may be associated with metronidazole resistance of H. pylori.

Base Sequence↗
PubMed1997

Vascular dysfunction induced by elevated glucose levels in rats is mediated by vascular endothelial growth factor.

The purpose of these experiments was to investigate a potential role for vascular endothelial growth factor (VEGF) in mediating vascular dysfunction induced by increased glucose flux via the sorbitol pathway. Skin chambers were mounted on the backs of Sprague-Dawley rats and 1 wk later, granulation tissue in the chamber was exposed twice daily for 7 d to 5 mM glucose, 30 mM glucose, or 1 mM sorbitol in the presence and absence of neutralizing VEGF antibodies. Albumin permeation and blood flow were increased two- to three-fold by 30 mM glucose and 1 mM sorbitol; these increases were prevented by coadministration of neutralizing VEGF antibodies. Blood flow and albumin permeation were increased approximately 2.5-fold 1 h after topical application of recombinant human VEGF and these effects were prevented by nitric oxide synthase (NOS) inhibitors (aminoguanidine and N(G)-monomethyl L-arginine). Topical application of a superoxide generating system increased albumin permeation and blood flow and these changes were markedly attenuated by VEGF antibody and NOS inhibitors. Application of sodium nitroprusside for 7 d or the single application of a calcium ionophore, A23187, mimicked effects of glucose, sorbitol, and VEGF on vascular dysfunction and the ionophore effect was prevented by coadministration of aminoguanidine. These observations suggest a potentially important role for VEGF in mediating vascular dysfunction induced by "hypoxia-like" cytosolic metabolic imbalances (reductive stress, increased superoxide, and nitric oxide production) linked to increased flux of glucose via the sorbitol pathway.

Animals↗
PubMed1997

Transradial coronary angiography and angioplasty in Chinese patients.

Radial artery punctures for diagnostic coronary angiography or coronary balloon angioplasty were performed in 211 patients with a success rate of 98% (207 patients). In the four failed transradial accesses, the procedure was accomplished via the transfemoral route. Major local vascular complications included one arteriovenous fistula, one pseudo-aneurysm, and one ischemic contracture of the right hand. Reduced radial pulses were noted in 25 (12%) patients at follow-up without ischemic manifestations. Transradial diagnostic coronary angiography was successfully completed in 184 (98%) of 187 patients. The technical success for balloon angioplasty was obtained in 73 (97%) of 75 patients. Clinical success was observed in 68 (91%) patients; balloon angioplasty resulted in one nonfatal myocardial infarction and four late deaths (3 cardiac and 1 stroke). We believe that transradial catheterization for diagnostic coronary angiography and balloon angioplasty in our relatively small built Chinese population is a safe and practical alternative approach.

Adult↗
PubMed1997

Cyclic AMP and cyclic GMP relax phorbol ester-induced contractions of rat aorta by different mechanisms.

This study was designed to test the hypothesis that 8-Br-cAMP and 8-Br-cGMP dependent relaxation of phorbol dibutyrate stimulated contractions of intact rat aorta are independent of changes in the level of myosin light chain phosphorylation. Phorbol dibutyrate stimulated contraction with a concomitant increase in myosin light chain phosphorylation in normal tissues and without an increase in myosin light chain phosphorylation in calcium-depleted tissues. Phorbol dibutyrate stimulated contractions in normal CaCl2-containing physiological salt solution were relaxed in a concentration-dependent manner by 8-Br-cAMP and 8-Br-cGMP. Phorbol dibutyrate-induced contractions in the absence of Ca2+ were only relaxed by 8-Br-cGMP; 8-Br-cAMP had no effect. The relaxation induced by 8-Br-cGMP was associated with a decrease in myosin light chain phosphorylation suggesting that cGMP-dependent protein kinase may alter the activity of either the myosin light chain kinase or phosphatase. The relaxation induced by 8-Br-cAMP was not associated with a decrease in phosphorylation suggesting that cAMP-dependent protein kinase may uncouple myosin light chain phosphorylation from force.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Acute effects of nitric oxide blockade with L-NAME on arterial haemodynamics in the rat.

1. We employed the technique of impedance spectral analysis to investigate the role of endogenous nitric oxide (NO) in the regulation of steady and pulsatile haemodynamics in Wistar Kyoto rat (WKY). 2. A total of 12 WKYs was anaesthetized with pentobarbitol sodium (40 mg kg-1, i.p.) and artificially ventilated with an animal respirator. The aortic pressure wave was monitored with a high fidelity Millar sensor, and aortic flow wave with an electromagnetic flow probe. The pressure and flow waves were subjected to Fourier transform for the analysis of impedance spectra. 3. The baseline cardiovascular parameters were mean arterial pressure (APm) 95 +/- 9 mmHg, heart rate (HR) 338 +/- 9 b.p.m., stroke volume (SV) 0.23 +/- 0.01 ml, cardiac output (CO) 77.8 +/- 1.6 ml min-1, total peripheral resistance (TPR) 98 +/- 11 (x10(3)) dyne s cm-5, characteristic impedance (Zc) 2046 +/- 141 dyne s cm-5, arterial compliance at mean AP (Cm) 3.78 +/- 0.22 microliters mmHg-1 and backward pulse wave (Pb) 12.9 +/- 0.6 mmHg. 4. An NO synthase inhibitor, NG-nitro-L-arginine monomethyl ester (L-NAME) was administered at graded intravenous doses. This agent caused dose-dependent increases in AP and TPR with decreases in HR. At an accumulative dose of 10 mg kg-1, APm was increased by 29 +/- 3 mmHg (+31%) and TPR by 49 +/- 6 (x10(3)) dyne s cm-5 (+50%), while HR was reduced by 37 +/- 5 b.p.m. (-11%) and CO by 10.4 +/- 0.8 ml min-1 (-14%). The pulsatile haemodynamics including Zc and Pb were slightly increased by 14-15%. Cm was decreased by 1.09 microliters mmHg-1 (-29%). L-NAME also did not significantly affect the ventricular work including the steady, oscillatory and total work. 5. Aminoguanidine, a specific inhibitor for inducible NO synthase (iNOS), in dose 10-60 mg kg-1 i.v. did not alter the AP, HR and other parameters. The result indicated that blockade of constitutive NOS, but not iNOS is involved in these changes. 6. Angiotensin II (Ang) in various infusion doses was used to produce a profile of AP increase similar to that caused by L-NAME. Ang remarkably increased Zc, while TPR was moderately elevated. The pattern of haemodynamic changes was different from that following L-NAME. 7. The results suggest that blockade of the endogenous NO affects predominantly the arterial pressure and peripheral resistance. The Windkessel functions such as arterial impedance and pulse wave reflection are slightly increased. Ventricular works are not significantly altered.

Animals↗