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C H Chang

Publications and source records attributed to C H Chang.

At least 595 records · Page 33Linked to original sources

Molecular properties of the androgen receptor in rat ventral prostate.

Results from these studies demonstrate that we have purified a protein from rat prostate cytosol that is similar to the beta-protein (complex II) but different from the alpha-protein (complex I) reported by Liao et al. The purified receptor was different from androgen binding protein (ABP) in that ABP has a faster dissociation rate (6 min), a lower pI value (4.6), and requires higher concentrations of ammonium sulfate for precipitation (40-50%) than the prostatic androgen receptor. It is not likely that we have purified a serum sex-steroid binding protein since no such protein is found in rat serum. This report presents a rapid and efficient procedure for the purification of androgen receptor from rat ventral prostate. However, the present procedure only allowed us to obtain a limited quantity of purified receptor from each preparation. It is obvious that we need to scale up the purification of the receptor in order to study in detail its physicochemical properties and to produce monospecific antibodies against the protein. This work is in progress. In addition, we have demonstrated that two affinity labels can be used to bind covalently to the androgen receptor. Most importantly, these compounds can be used to characterize androgen receptors under both nondenaturing and denaturing conditions and represent useful tools for future work with androgen receptor proteins and androphilic proteins in general.

Affinity Labels↗

Jaundice after open heart surgery: a prospective study.

One hundred and fifty four consecutive adult patients having cardiac surgery for a variety of cardiac lesions were evaluated prospectively for postoperative jaundice, those with a raised preoperative serum bilirubin concentration (greater than 34 mumol/l or 2 mg/100 ml) being excluded. The incidence of early postoperative jaundice, as defined by a serum bilirubin concentration of 50 mumol/l (3.0 mg/100 ml) or greater, was 23.4%. The jaundice was mild (bilirubin concentration 51-100 mumol/l (3.0-6.0 mg/100 ml] in 26 patients (16.9%) and moderate to severe (greater than 100 mumol/l (6.0 mg/100 ml] in 10 patients (6.5%). Important contributing factors were the preoperative severity of right heart failure (raised right atrial pressure at heart catheterisation) and hypotension or hypoxaemia and the amount of blood transfused during or shortly after surgery. Age, sex, underlying cardiac lesion, whether halothane was used, operative procedure, duration of cardiopulmonary bypass, and presence or absence of hepatitis B surface antigen were not predictive of postoperative jaundice.

Adolescent↗

Renal transplant rejection: sonographic evaluation in children.

The ability to detect renal rejection sonographically was studied in 42 pediatric renal transplant patients over a 33-month period. Sonography was not helpful in detecting rejection when the donor was less than five years of age. When the donor was over five years of age, a combination of sonographic findings allowed detection of rejection with a greater specificity than has been reported previously. The combination of three or more of the sonographic findings (increased renal volume 30% over the baseline value; enlarged, broadened, rectangular medullary pyramids [rays]; a reduction or absence of the central sinus echoes, and altered echogenicity in the renal parenchyma) indicated rejection with 97% specificity and 58% sensitivity. Radionuclide imaging with Tc-99m DTPA gave approximately the same sensitivity (60%) but was less specific (88%). By excluding rejection with the absence of the sonographic findings, it was possible to suggest acute tubular necrosis in some patients. It was also possible to detect the complications of renal transplantation, but sonography did not detect small ruptures of the kidney as a part of the rejection phenomenon.

Adolescent↗

Effects of sodium molybdate on the androgen receptor from the R3327 prostatic tumor.

The present study describes the effects of sodium molybdate on several physicochemical properties of the androgen receptor from the Dunning R3327 prostatic tumor. Molybdate was found to stabilize the steroid-binding activity of the receptor. Maximum binding activity was found with concentrations of 10 mM molybdate or greater. Density gradient and gel filtration analyses of the receptor revealed an 8.5-9.0S, 68A form (mol wt, approximately 265,000-275,000) in either the presence or absence of molybdate (20 mM) when determined under low ionic conditions. Under high ionic conditions (400 mM KCl), the receptor was maintained in a similar form (8.5-9.0S; 72-73A; mol wt, approximately 275,000-295,000) in the presence of molybdate; however, it disaggregated to a smaller 4.4S, 61 A form (mol wt, approximately 120,000) in the absence of molybdate. Affinity labeling of the receptor with 17 beta-[(bromoacetyl)oxy]-[1,2,4,5,6,7,16,17-3H8]5 alpha-androstan-3-one showed a mol wt of 118,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Molybdate inhibited the salt-induced transformation of the receptor to a DNA-binding state, but did not inhibit the DNA binding of the receptor transformed previously in the absence of molybdate. These studies suggest that sodium molybdate stabilizes the steroid-binding activity of the androgen receptor in an aggregated nontransformed state.

Animals↗

Cardiac dimensions and motion shortly after mitral valve surgery.

We studied 71 adult patients echocardiographically both before and 2-16 days (mean 8 days) after mitral valve surgery to systematically evaluate the early postoperative changes in cardiac dimensions and motion. The patients were divided into 4 groups: group I with predominant mitral stenosis (MS) (26 patients), group II with predominant mitral insufficiency (MI) (12 patients), group III with MS + MI (16 patients) and group IV with combined mitral and aortic valvular disease (17 patients). After operation the left atrial dimension at endsystole decreased (mean +/- standard deviation, 56 +/- 12 mm vs 46 +/- 11 mm, p less than 0.001), but did not completely normalize in the majority of patients. The left ventricular dimension at enddiastole decreased in group II from 67 +/- 12 mm to 54 +/- 5 mm (p less than 0.01) and in group IV from 59 +/- 13 mm to 54 +/- 13 mm (p less than 0.01), but increased in group I from 43 +/- 8 mm to 46 +/- 9 mm (p less than 0.05). Mitral EF slope increased from 15 +/- 11 mm/sec to 52 +/- 20 mm/sec (p less than 0.001) after commissurotomy, and decreased from 136 +/- 61 mm/sec to 66 +/- 30 mm/sec (p less than 0.05) after annuloplasty. However, the postoperative means were subnormal in these subgroups. Paradoxical or hypokinetic septal motion occurred in 5/71 (7%) before and 50/71 (70%) after operation. We conclude that: 1) partial normalization of cardiac dimensions and subnormal mitral EF slopes shortly after mitral valve surgery suggest a residual pressure gradient across the mitral valve as well as partial irreversibility of the heart after longstanding mechanical overloading, and 2) postoperative abnormal septal motion, which may be caused by pericardiotomy, can occur after any type of open heart surgery.

Adolescent↗

Purification and characterization of the androgen receptor from rat ventral prostate.

The androgen receptor has been purified from rat ventral prostate cytosol by a combination of differential DNA-Sepharose 4B chromatography and testosterone 17 beta-hemisuccinyl-3,3'-diaminodipropylamine-Sepharose 4B affinity chromatography. Approximately 8 micrograms of protein was obtained from 38 g of rat ventral prostate, with a yield of 24%. The receptor was purified approximately 120 000-fold. Silver nitrate staining of a sodium dodecyl sulfate (NaDodSO4)-polyacrylamide gel revealed a major polypeptide band migrating at 86 000 daltons. Affinity labeling of a partially purified receptor preparation with either 17-hydroxy-17 alpha-[3H]methyl-4,9,11-estratrien-3-one or 17 beta-hydroxy-[1,2,4,5,6,7,16,17-3H8]-5 alpha-androstan-3-one 17-(2-bromoacetate) produced a major band of radioactivity migrating at 86 000 daltons on a NaDodSO4 gel. Under nondenaturing conditions, a Mr of 85 000 was determined by gel filtration (42 A) and sucrose gradient sedimentation analysis (4.5 S). The purified receptor had an isoelectric point of 6.3 [3H]-4,5 alpha-Dihydrotestosterone, bound to the purified receptor, was displaced with 4,5 alpha-dihydrotestosterone greater than testosterone much greater than progesterone greater than 5 alpha-androstane-3 alpha, 17 beta-diol greater than 17 beta-estradiol greater than cortisol. A number of physicochemical properties of the purified receptor were similar to those of the receptor in crude cytosol.

Androgens↗

Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study.

Recently, the RTOG and ECOG concluded a joint randomized study on malignant gliomas that was in progress for the past five years. A total of 626 patients entered this protocol. Sixty-seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial. The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone. The four options were: (1) control radiation; 6000 rad/6-7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1-2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl-CCNU (125 mg/m2/day orally X 1 and repeat methyl-CCNU every 8 weeks), and DTIC (150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks). All pertinent patient characteristics were studied and several important prognostic factors have been identified. Notably, age, histologic type (Astrocytoma with anaplastic foci, versus glioblastoma multiforme), initial performance status, time since first symptoms and presence or absence of seizure. At this time, it appeared that there was no treatment option which was significantly better than the control. The study identified that age was the most important prognostic factor. Patients who were younger than age 40 years had an 18-month survival of 64%, patients who were age 40-60 years had an 18-month survival of 20%, and patients who were older than age 60 had an 18-month survival of 8%. The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40-60-year-old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups (P = 0.01, one-sided). Similarly, methyl-CCNU + DTIC was suggestively better than the control (P = 0.08, one-sided). The higher radiation dose, 7000 rad/8-9 weeks appeared to give no significantly better survival over the control dose option. Both BCNU and methyl-CCNU + DTIC produced some toxicity. The combination of methyl-CCNU + DTIC was more toxic than BCNU, producing severe or worse thrombocytopenia in 23% of the patients as compared to 6% on BCNU.

Adult↗

Identification of a key structural feature of cobalt(III)-bleomycins: an exogenous ligand (e.g. hydroperoxide) bound to cobalt.

A series of cobalt(III) complexes of the anticancer antibiotic bleomycin has been prepared. Mass spectrometry and enzymatic analysis show that the green cobalt-bleomycin complex contains a hydroperoxide (-OOH) group bound to cobalt with unusual stability. Under appropriate conditions, cobalt-bleomycins containing other monodentate ligands to cobalt can be formed; fast-atom bombardment mass spectra of such complexes show peaks for cobalt-bleomycin at the expected mass, and also peaks for the intact complexes at the required higher mass.

Bleomycin↗

Kinetic studies of adenosine kinase from L1210 cells: a model enzyme with a two-site ping-pong mechanism.

Purified adenosine kinase from L1210 cells displayed substrate inhibition by high concentrations of adenosine (Ado), ATP, and MgCl2. When incubated with ATP and MgCl2, the enzyme was phosphorylated, and the phosphorylated kinase transferred phosphate to adenosine in the absence of ATP and MgCl2. Substrate binding, isotope exchange, and kinetic studies suggested that the enzyme catalyzes the reaction by means of a two-site ping-pong mechanism with the phosphorylated enzyme as an obligatory intermediate. Among many possible pathways within this mechanism probably a random-bi ordered-bi route is the preferred sequence in which the two substrates, adenosine and MgATP, bind in a random order to form the ternary complex MgATP . E . Ado followed by the sequential dissociation of MgADP and AMP. Dissociation constants of various enzyme-substrate and enzyme-product complexes and the first-order rate constant of the rate-limiting step were estimated.

Adenosine↗

Effect of baclofen enantiomorphs on the spinal trigeminal nucleus and steric similarities of carbamazepine.

The seemingly structurally different drugs, baclofen and carbamazepine, have a similar neurophysiologic effect on the cat spinal trigeminal nucleus and a similar clinical effect in the amelioration of trigeminal neuralgia pain. In this investigation, we report on the enhancement of segmental inhibition by carbamazepine and l-baclofen; d-baclofen produced no effect on segmental inhibition. Doses of l-baclofen one fifth its equivalent racemic dosage produced a much greater enhancement of segmental inhibition. d-Baclofen, when given prior to l-baclofen, blocked the effect of l-baclofen on segmental inhibition and the unconditioned response at previously effective doses. Pretreatment with d-baclofen also blocked the effect of subsequent carbamazepine on segmental inhibition, but had no effect on the unconditioned response. Crystallographic evaluation of carbamazepine and the enantiomorphs of baclofen revealed a surprisingly good fit of baclofen isomers to moieties of the carbamazepine molecule. The results suggest that the baclofen enantiomorphs and carbamazepine have a common mechanism of action in the cat spinal trigeminal nucleus, and that d-baclofen, though inactive, is capable of interfering with the effect of l-baclofen and to a lesser extent with carbamazepine.

Animals↗

Physicochemical characterization of the androgen receptor in rat uterine cytosol.

In this manuscript a number of physicochemical and DNA-binding properties of the androgen receptor from rat uterus were characterized. The dissociation of [3H]testosterone from the receptor followed first order kinetics, with a half-time dissociation rate of approximately 48 h at 0 C. Maximum binding was maintained at pH 7. Ammonium sulfate precipitated the receptor at concentrations between 25-40% saturation. Gel filtration and sucrose gradient analysis revealed a 62 A, 6S binding component (mol wt, 167,000; frictional ratio, 1.71) in both the absence and presence of the protease inhibitor leupeptin. Isoelectric focusing revealed an isoelectric point of 5.9. The receptor bound to DEAE-agarose, heparin-Sepharose, and hydroxylapatite. Increased receptor binding to phosphocellulose and DNA-cellulose was observed after heat treatment at 24 C for 30 min. These results demonstrate that the uterine androgen receptor has many properties similar to those of androgen receptors in male target tissues.

Ammonium Sulfate↗

Unexplained severe pulmonary hypertension in the older age group.

Two cases of unexplained severe pulmonary hypertension were seen in the older age group. Although classified as primary pulmonary hypertension, the clinical course of these patients was very unusual because of their age and relatively long duration of diseases. The long period of follow-up allowed assessment of both the difficulties of making a definite diagnosis of primary pulmonary hypertension in the older age group and the noninvasive methods which were particularly helpful. Making the diagnosis of primary pulmonary hypertension in the older age group is important because there are now drugs which can ameliorate the severity of pulmonary hypertension.

Aged↗

Scanning and transmission electron microscopic studies on isolated ruptures of chordae tendineae.

Electron microscopic studies of chordae tendineae of the mitral valve were carried out in 17 patients who underwent mitral valve replacement due to a spontaneously isolated rupture of chordae tendineae. The normal chordae, used as the control group, were obtained at autopsy from 5 patients who died from extracardiac causes and were compared with the ruptured chordae. In all patients with chordal rupture, scanning electron microscopy showed perforations of the chordae tendineae, with extensive desquamation and disruption of the endothelial cells and wide-spread destruction of the collagen fiber bundles in the central collagenous core. These pathological findings were not observed in the normal chordae from the control group. Transmission electron microscopy showed that the ruptured chordae were characterized by heterogeneous collagen fibrils with intrinsic structural alterations and disorganization in fibril arrangement. There was a wide variation in the diameters of collagen fibrils which always showed abnormal morphology, with abnormally large, peculiarly shaped fibrils. Apparent loss and/or a disordered arrangement of the typical periodicity of the fibrils were frequently observed. In addition, various degrees of degenerative changes of collagen tissue were often present. These abnormalities were never seen in the fibrils of the normal chordae, and were observed consistently in both the fibrils of the ruptured chordae and in the macroscopically intact chordae in the group with spontaneous rupture of chordae tendineae. These results suggest that a defective organization of collagen into fibrils and fibers, associated with secondary degeneration of collagen within the central collagenous core of the chordae tendineae, are important pathogenetic mechanisms for spontaneously isolated ruptures of chordae tendineae.

Adolescent↗

The relationship of transmembrane potential to surface morphology of human atrial muscle and cardiac hemodynamics.

A correlative study of transmembrane potential characteristics, surface morphological features of human atrial muscle, and cardiac hemodynamics was carried out in 41 patients, who were divided into 2 groups based on the level of the mean maximum diastolic potentials (MDP). Group A consisted of 19 patients with MDP values ranging from -60.0 to -82.0 mV (mean +/- S.D. = -65.70 +/- 6.63 mV). Group B included 22 patients who had abnormally low MDP (range -36.0- -58.5 mV, mean +/- S.D. = -48.14 +/- 6.72 mV). The differences in electrophysiological data were statistically significant. However, there were no significant differences in the hemodynamic data between the 2 groups. Furthermore, there was poor correlation between the electrophysiological and hemodynamic data in both groups. In group A, scanning and transmission electron microscopy revealed either no changes or only mild alterations in the surface morphology of the atrial myocardium. Various degrees of surface morphological changes, including a focal loss of the endothelium which was always associated with endocardial fibrosis, irregular thickening and lamination of the glycocalyx, disruption of the sarcolemma and complete destruction of the surface membrane structures were more often observed in group B. These results provide valuable evidence that sarcolemmal changes may underlie the electrophysiological alterations in diseased human atria. We suggest that the principal pathogenetic mechanisms leading to the transmembrane potential changes are the altered surface morphology of atrial myocardial cells, resulting from underlying disease processes.

Adolescent↗