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Biomedical subjects

K C Chang

Publications and source records attributed to K C Chang.

At least 109 records · Page 6Linked to original sources
PubMed1997

Developmental expression and 5' end cDNA cloning of the porcine 2x and 2b myosin heavy chain genes.

Muscle research on farm animals suffers from a lack of basic molecular probes and immunochemical reagents. To complete the cloning of a comprehensive range of isoform-specific postnatal myosin heavy chain (MyHC) probes from the pig, we report here on the 5 '-end cDNA isolation, identification, and in vivo characterization of the porcine equivalent of the 2x (fast oxidative-glycolytic) and 2b (fast glycolytic) MyHC isoforms. Comparative analyses of primary nucleotide and deduced amino acid sequences of the porcine slow, 2a, 2x, and 2b cDNAs showed that the 2x and 2b isoforms were most homologous with each other and the slow isoform was the least similar. At or just after birth, at least 3 postnatal muscle fiber types (slow/beta, 2a, and 2x) were present. MyHC 2x expressing fibers were arranged distinctively as large outer rings, each surrounding an inner ring of 2a fibers, which in turn circumscribed one or more central slow fibers. Subsequently, different muscles expressed at different times the MyHC 2b isoform such that by 10 weeks, 2b fibers became the most dominant fiber type, in size and number in nearly all muscles examined except for its notable absence in the soleus muscle. Co-expression of two or more MyHC isoforms within the same fiber was not a feature of porcine muscles unlike that observed in rat and human muscles. For the first time, porcine muscle fibers can now be classified into 4 adult phenotypes (slow/beta 2a, 2x, and 2b) according to the expression of specific MyHC isoforms.

Amino Acid Sequence↗
PubMed1997

Prevalence of human papillomavirus in middle ear carcinoma associated with chronic otitis media.

Squamous cell carcinoma of the middle ear (MESCC) is an uncommon tumor and is associated with a history of long-term chronic otitis media (COM) in most cases. Although the human papillomaviruses (HPVs) have been implicated in many human neoplasms, its role in the pathogenesis of MESCC has not been studied. Polymerase chain reaction (PCR) using consensus primers for the detection of HPV types 6, 11, 16, 18, 31, 33, 52b, and 58 was applied in screening fourteen cases of MESCC from archival material. Further subtyping was performed by restriction enzyme digestion of PCR products and by in situ hybridization method on tissue sections. Of the fourteen cases of MESCC, eleven were found to have HPV DNA. HPV-16 was detected in all positive cases. Five cases revealed both HPV-16 and -18. A history of long-term COM (> 3 years) was found in thirteen of the cases. This is the first report to localize HPV-16/18 in MESCC on both the tissue level and the molecular level. The high prevalence of HPV in COM-associated MESCC therefore provides a good model to explain the pathogenesis of chronic-inflammation-related human malignancies.

Adult↗
PubMed1996

Exponentially tapered T-tube model in the characterization of arterial non-uniformity.

There is no question that geometric and elastic tapering is the rule of the nature of the mammalian arterial system. In this investigation, we determine the role of an exponentially tapered T-tube model to characterize the non-uniform nature and physical properties of the vasculature. The tapering feature could be inferred to show a connection between characteristic impedance at the distal of the tube and that at the entrance of the tube. Pulsatile pressure and flow signals of the ascending aorta were measured in 12 closed-chest, anesthetized dogs. This non-uniform T-tube model fits the measured aortic pressure waveform well. The mathematical and experimental model impedance spectra are similar. In the basal state, the distal characteristic impedance is 9.5% higher than the input characteristic impedance. The input characteristic impedance estimated in the model is compatible with that calculated by averaging high-frequency moduli of impedance data points obtained from the ratio of the corresponding harmonics of pressure and flow. Furthermore, the exponentially tapered T-tube model has a close estimate in wave transit time when compared with that computed by the impulse response of the filtered aortic input impedance. These data suggest that inclusion of tube tapering improves the mathematical model so that it is capable of characterizing the non-uniform nature of the arterial system. We conclude that the non-uniform properties of wave-transmission paths play an important role in governing the behavior of an asymmetric T-tube for the representation of the arterial system.

Animals↗
PubMed1996

Alpha1-adrenergic receptor subtype mRNAs are differentially regulated by alpha1-adrenergic and other hypertrophic stimuli in cardiac myocytes in culture and in vivo. Repression of alpha1B and alpha1D but induction of alpha1C.

The three cloned alpha1-adrenergic receptor (AR) subtypes, alpha1B, alpha1C, and alpha1D, can all couple to the same effector, phospholipase C, and the reason(s) for conservation of multiple subtypes remain uncertain. All three alpha1-ARs are expressed natively in cultured neonatal rat cardiac myocytes, where chronic exposure to the agonist catecholamine norepinephrine (NE) induces hypertrophic growth and gene transcription. We show here, using RNase protection, that the alpha1-AR subtype mRNAs respond in distinctly different ways during prolonged NE exposure (12 72 h). Alpha1B and alpha1D mRNA levels were repressed by NE, whereas alpha1C mRNA was induced. Changes in mRNA levels were mediated by an alpha1-AR, were not explained by altered mRNA stability, and were reflected in receptor proteins by [3H]prazosin binding. alpha1-AR-stimulated phosphoinositide hydrolysis and myocyte growth were not desensitized. Three other hypertrophic agonists in culture, endothelin-1, PGF2alpha, and phorbol 12-myristate 13-acetate, also induced alpha1C mRNA and repressed alpha1B mRNA. In myocytes from hearts with pressure overload hypertrophy, alpha1 mRNA changes were identical to those produced by NE in culture. These results provide the first example of a difference in regulation among alpha1-AR subtypes expressed natively in the same cell. Transcriptional induction of the alpha1C-AR could be a mechanism for sustained growth signaling through this receptor and is a common feature of a hypertrophic phenotype in cardiac myocytes.

Adrenergic alpha-Agonists↗
PubMed1996

Immunohistochemical localization of Mcl-1 and bcl-2 proteins in thymic epithelial tumours.

Mcl-1 protein is a new member of the bcl-2 protein family. It is believed to be a blocker of apoptosis but might be different from bcl-2 in the control of apoptosis. Using immunostaining of formalin-fixed, paraffin-embedded sections, we investigated the expression of Mcl-1 in 42 thymic epithelial tumours: three medullary thymomas, five mixed thymomas, seven cortical thymomas, eight well-differentiated thymic carcinomas, 14 squamous cell carcinomas, four lymphoepithelioma-like carcinomas and one undifferentiated carcinoma, bcl-2 immunocytochemical localization was also performed for comparison. High-grade thymic carcinomas, especially squamous cell carcinomas, revealed more intense Mcl-1 immunoreactivity as compared to other subtypes (P < 0.001). In cases that co-expressed Mcl-1 and bcl-2, the less differentiated cells had more intense expression of bcl-2, while the more differentiated cells displayed stronger Mcl-1 immunoreactivity. The differential expression of Mcl-1 and bcl-2 in neoplastic cells provides evidence that these proteins may play different roles in the processes of programmed cell death in thymic neoplasms. The finding that thymic carcinomas have stronger immunoreactivity for Mcl-1 indicates that this protein could be a useful marker to differentiate aggressive thymic epithelial tumours from indolent ones.

Carcinoma↗
PubMed1996

Impaired Ca2+ handling is an early manifestation of pressure-overload hypertrophy in rat hearts.

Both cytosolic free Ca2+ ([Ca2+]i) decline and myocardial relaxation are slowed in severe hypertrophy and heart failure. However, it is not certain whether this occurs in mild to moderate hypertrophy. Therefore, we tested the hypotheses that slowing of [Ca2+]i decline 1) occurs in mild to moderate hypertrophy, 2) occurs in the absence of slowed relaxation, and 3) is related to the degree of hypertrophy. Experiments were performed on isolated rat hearts subjected to pressure overload. Indo 1 fluorescence was used as an index of [Ca2+]i. [Ca2+]i decline and myocardial relaxation were assessed by the time constant of exponential [Ca2+]i decline (tau Ca) and left ventricular (LV) pressure decline (tau p), respectively. Mean tau Ca was significantly increased in hearts from banded rats compared with sham-operated rats (59 +/- 13 vs. 45 +/- 5 ms, P = 0.03). In contrast, there was no difference in mean tau p (28 +/- 3 vs. 29 +/- 5 ms, P = not significant). There was a linear relationship between tau Ca and LV dry weight (r = 0.79). In summary, slowing of the [Ca2+]i transient decline occurred in mild to moderate hypertrophy. However, LV relaxation was unaffected. Furthermore, slowing of the [Ca2+]i transient decline was closely related to the degree of LV hypertrophy. These data suggest that slowing of [Ca2+]i decline is an early manifestation of pressure-overload hypertrophy that precedes slowing of relaxation.

Animals↗
PubMed1996

Papillary cystic tumor of the pancreas in children.

Papillary cystic tumor of the pancreas, so-called Frantz tumor, is a very rare tumor in children. Only 157 cases had been reported since 1959. The clinical manifestations of this disease are usually a slowly growing abdominal mass with or without abdominal pain. It occurs predominantly in young females, and its pathogenesis is still unknown. Surgical resection is usually curative, and its prognosis is excellent. Four adolescent girls with acute or chronic abdominal pain were found to have papillary cystic tumor of the pancreas at our hospital in the past 4 years. They all have a variable clinical presentation. Papillary cystic tumor of the pancreas should therefore be considered one of the differential diagnoses of abdominal pain or abdominal mass in adolescent girls.

Abdominal Pain↗
PubMed1996

Partially unroofed coronary sinus and persistent left superior vena cava: intracardiac echocardiographic observation.

Unroofed coronary sinus, a rare congenital anomaly first described by Raghib and colleagues1 in 1965, is a result of an embryologic error involving imperfect or complete failure of development of the left atriovenous fold, which is manifested as a focal (fenestration or partial unroofing of the coronary sinus) or complete absence of the coronary sinus septum. Before the era of echocardiography, precise diagnosis of this anomaly was possible only during surgical procedure or at autopsy. Since the advent of the echocardiography, several studies have reported the usefulness of two-dimensional transthoracic and transesophageal echocardiography in the diagnosis of unroofed coronary sinus. We describe the intracardiac echocardiographic delineation of partially unroofed coronary sinus and persistent left superior vena cava in a patient with atrioventricular nodal reentrant tachycardia. Incidental finding of the dilated coronary sinus during radio frequency ablation of the tachycardia led to the diagnosis of this unusual anomaly.

Adult↗
PubMed1996

Effects of nitric oxide on detrusor relaxation.

PURPOSE: Recently we (1994) reported the photo-induced adequate nitric oxide (PIANO) system, in which an NO- or NO2-carrying molecule which has been photoactivated to release NO, could be exploited to investigate the role of NO in various smooth muscle functions. This study was designed to characterize the effect of nitric oxide (NO) exploiting PIANO on rat detrusor relaxation by isometric tension recording and measuring changes in cGMP content. MATERIALS AND METHODS: Exposure to ultraviolet light was used (1 to 60 seconds) to evoke PIANO in the presence of streptozotocin, an NO-carrier, and N omega-nitro-L-arginine (L-NOARG), an NO2-carrier. During relaxation the cyclic guanosine monophosphate (cGMP) content was measured by radioimmunoassay. RESULTS: Rat detrusor strips were reversibly relaxed upon NO generation via PIANO. Pyrogallol, an O2 generator, significantly (p < 0.01) diminished PIANO-mediated relaxation. During PIANO-mediated relaxation, the tissue level of cyclic GMP significantly (p < 0.05) increased over that of the control. Furthermore, methylene blue, a guanylate cyclase inhibitor, significantly (p < 0.01) inhibited both the relaxation and the increase of cGMP. CONCLUSION: We concluded that rat detrusor muscle was capable of responding to NO, and these findings might lead to a treatment for bladder instability and detrusor hyperreflexia, by the use of intravesical instillation of NO donors.

Animals↗
PubMed1996

Characterization of arterial hemodynamics in rats with established hypertension.

In long-term hypertension, hemodynamic alterations are associated with functional and structural changes in the cardiovascular system. The technique of arterial impedance spectral analysis has long been used to characterize the arterial hemodynamics of steady and pulsatile components in human hypertension. Although rats with spontaneous hypertension (SHR) are the most common model for studies of primary hypertension, characterization of complete hemodynamic parameters has not been accomplished in this animal model. In the present experiment, aortic flow and pressure waves were recorded in anesthetized, open-chest and ventilated rats. Arterial impedance spectral analysis was employed to obtain steady and pulsatile hemodynamic parameters. A total of 26 SHRs (22-24 wk) and 22 age-matched normotensive WKYs was used. The purpose was to provide a comprehensive analysis of arterial hemodynamics in rats with established hypertension. The SHR had higher arterial pressure (50% increase over the control) than WKY. The total peripheral resistance was elevated by 57%. Stroke volume was decreased by 23% and heart rate increased by 18% without a significant change in cardiac output. The characteristic impedance was increased by 43%, while arterial compliance was decreased by 52%. There were also big rises in ventricular work and wave reflection. The results provide quantitative analysis of the alteration in arterial hemodynamics of steady and pulsatile components in rats with established hypertension. In long-term hypertension, the hemodynamics reflect functional abnormalities in the resistance and Windkessel vessels.

Animals↗
PubMed1995

Is alpha-adrenoceptor blockade responsible for atropine flush?

Toxic amounts of atropine usually, and therapeutic doses occasionally, dilate cutaneous blood vessels, especially those in the blush area (atropine flush). However, the mechanism of this anomalous vascular response is unknown. We, therefore, investigated this action of atropine not only in functional but also in binding studies with isolated rat aorta and brain, respectively. Endothelium-denuded rat thoracic aortic rings were contracted with norepinephrine, U46619 (9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha, thromboxane A2 receptor agonist) and KCl, and the relaxation in response to atropine was recorded. The norepinephrine-, but not the U46619- or KCL-mediated contraction was relaxed by atropine. Atropine caused a rightward parallel shift of the phenylephrine concentration-contraction curve with a pA2 value of 6.57 (slope 0.58), but did not affect the concentration-contraction curve for U46619. In rat cerebral cortex homogenates, atropine displaced [3H]prazosin with Ki values of 3.33 nM and 0.19 microM, respectively. These results suggest that even though atropine has low affinity for the alpha-adrenoceptor, it possesses characteristics similar to those of a competitive ligand for the alpha-adrenoceptor. Thus, atropine, especially at high concentrations, has direct alpha-adrenoceptor blocking activity, which may account, at least in part, for atropine flush.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

The inhibitory effect of apolipoprotein E4 on neurite outgrowth is associated with microtubule depolymerization.

Evidence is presented for the differential effects of two isoforms of apolipoprotein (apo) E, apoE3 and apoE4, on neurite outgrowth and on the cytoskeleton of neuronal cells (Neuro-2a) in culture. In the presence of a lipid source, apoE3 enhances and apoE4 inhibits neurite outgrowth. Immunocytochemical studies demonstrate that there is a higher concentration of apoE3 than apoE4 in both the cell bodies and neurites. Cells treated with apoE4 showed fewer microtubules and a greatly reduced ratio of polymerized to monomeric tubulin than did cells treated with apoE3. The effect of apoE4 on depolymerization of microtubules was shown by biochemical, immunocytochemical, and ultrastructural studies. The depolymerization of microtubules and the inhibition of neurite outgrowth associated with apoE4 suggest a mechanism whereby apoE4, which has been linked to the pathogenesis of Alzheimer's disease, may prevent normal neuronal remodeling from occurring later in life, when this neurodegenerative disorder develops.

Actins↗
PubMed1995

Cloning and in vivo expression of the pig MyoD gene.

The complete sequence of the pig MyoD gene has been determined through the isolation and characterization of a 17 kb genomic clone. The deduced amino acid sequence shows relative conservation of about 90% with the MyoD sequences determined in other mammalian species, though there are several non-conservative changes scattered throughout the C-terminus. In situ hybridization on pig embryos (20-30 days post coitum) showed that MyoD expression was confined to myotomes and skeletal muscle masses.

Amino Acid Sequence↗
PubMed1995

Impedance and wave reflection in arterial system: simulation with geometrically tapered T-tubes.

The aortic input impedance is simulated by an asymmetric T-tube model loaded with complex loads. A geometric tapering is incorporated to represent the vasculature, assuming a triangular distribution of the wave transmission paths. Parametric analyses using physiological data demonstrate that the predicted impedance and reflection coefficient spectrum (RCS) closely mimic the experimental data. The simulation also reveals several significant features. As diameter tapering can minimise the presence and influence of wave reflections, the impedance modulus stays relatively constant with two distinct minima. The frequency of first minimum of impedance modulus is evidence of the tube elasticity and load compliance in the lower extremity, and the frequency of second minimum is evidence of those in the upper extremity. The high-frequency portion of the impedance modulus is affected by the tube elasticity, but not by the load compliance. The impedance spectrum at higher frequencies shows no notable fluctuations corresponding to a decrease in blood or wall viscosity. Furthermore, the low-frequency range in RCS is dominated by the longer lower body tube, and the high-frequency range by the shorter upper body tube. This geometrically tapered T-tube is considered a more natural model for the description of the systemic arterial system.

Arteries↗
PubMed1995

Molecular characterization of a developmentally regulated porcine skeletal myosin heavy chain gene and its 5' regulatory region.

Members of the myosin heavy chain (MyHC) gene family show developmental stage- and spatial-specificity of expression. We report on the characterization and identification of a porcine skeletal fast MyHC gene, including its corresponding 5' end cDNA and 5' regulatory region. This MyHC isoform was found exclusively in skeletal muscles from about the last quarter of gestation through to adulthood. Expression of this isoform was higher postnatally and its spatial distribution resembled a rosette cluster; each with a ring of fast fibres surrounding a central slow fibre. This rosette pattern was absent in the adult diaphragm but about 20% of the fibres continued to express this MyHC isoform. Further in vivo expression studies, in a variety of morphologically and functionally diverse muscles, showed that this particular skeletal MyHC isoform was expressed in fast oxidative-glycolytic fibres, suggesting that it was the equivalent of the fast IIA isoform. Two domains in the upstream regulatory region were found to confer differentiation-specific expression on C2 myotubes (-1007 to -828 and -455 to -101), based on in vitro transient expression assays using the chloramphenicol acetyltransferase (CAT) reporter gene. Interestingly, for high levels of CAT expression to occur, a 3' region, extending from the transcriptional start site to part. of intron 2, must be present in all the DNA constructs used.

Aging↗
PubMed1995

Effects of dicentrine on the mechanical properties of systemic arterial trees in dogs.

We evaluated the effects of dicentrine on the physical properties of systemic arterial trees. Dicentrine, isolated from Lindera megaphylla, was identified as a potent, selective alpha 1-adrenoceptor antagonist. We used high-fidelity multisensor catheter to measure the ascending aortic pressure and flow signals in 9 mongrel dogs. A succinct T-tube model with vascular nonuniformity was adopted to relate the pulsatile pressure and flow waves. The model-estimated parameters were capable of representing the mechanical properties of the blood vessel walls. Dicentrine had a beneficial effect on the rigidity of head and body circulation, respectively. There were great improvements not only in the tube distensibility and wave transmission time, but also in the peripheral load compliance and resistance. In global circulation that was defined as the parallel combination of head and body circulation, dicentrine significantly reduced values in characteristic impedance of the ascending aorta from 164 +/- 67 to 105 +/- 43 dynes/s/cm5, and in wave reflection factor from 0.46 +/- 0.14 to 0.36 +/- 0.13, and in total peripheral vascular resistance from 4,751 +/- 1,226 to 3,581 +/- 1,277 dynes/s/cm5. On the other hand, total peripheral load compliance was increased from 0.2950 +/- 0.1794 to 0.4457 +/- 0.2199 ml/mm Hg. Cardiac output (CO) and heart rate (HR) remained unchanged, however. Dicentrine had an impact on the mechanical properties of Windkessel vessels and resistance vessels in the systemic circulation.

Adrenergic alpha-Antagonists↗
PubMed1994

Unified modeling framework of cell death due to bubbles in agitated and sparged bioreactors.

A modeling framework is proposed to assess the detrimental effects of air sparging and other bubble phenomena (vortex entrainment, coalescence, bursting) on freely suspended cells in an aerated, agitated bioreactor. It is assumed that cells may be rendered nonviable by bubble breakup/coalescence within the medium, by bubble formation at the sparger, or by bubble bursting at the free surface. Some plausible mechanisms are argued from the energetic view point. The dominant parameters in each case are the cell-bubble encounter rate and the bubble breakup/bursting rate. These inactivation processes lead to a Michaelis-Menten expression for the specific cell death rate, which is shown to be linearly proportional to the specific bubble interfacial area (total bubble surface area per unit volume of media). By using published viable cell concentration data for retarded growth of mammalian cells due to sparging, the interfacial area correlation is demonstrated. The method is generalized to aerated bioreactor conditions. The article offers a unique, consistent perspective on how cell death can be viewed.

Air↗