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Biomedical subjects

C H Chang

Publications and source records attributed to C H Chang.

At least 451 records · Page 25Linked to original sources

Caged ATP potentiates guanylate cyclase activity stimulated by atrial natriuretic factor in rat lung membranes.

ATP increases both basal and atrial natriuretic factor (ANF)-stimulated guanylate cyclase activities. The present studies were designed to compare the effect of adenosine-5'-triphosphate, P3-1-(2-nitrophenyl)-ethyl ester (caged ATP), a photolabile derivative of ATP, with ATP. Caged ATP increases both basal and ANF-stimulated enzyme activities in a concentration-dependent manner, but is more potent than ATP. The effect of caged ATP significantly decreases after it is photo-converted to ATP by UV irradiation. These observations suggest that the caged group introduces a hydrophobic interaction thereby facilitating guanylate cyclase activation.

Adenosine Triphosphate↗

Malignant astrocytic gliomas in children.

Between 1957 and 1980, 54 children less than 20 years of age with a diagnosis of glioblastoma multiforme or malignant astrocytoma were treated. All patients had a minimum follow-up period of 5 years. Twenty-seven patients had glioblastoma multiforme and 27 had malignant astrocytoma. The median age was 8 years for glioblastoma multiforme patients and 10 years for malignant astrocytoma patients. All patients received radiation therapy, but two died of postoperative complications and did not complete the treatment. The Kernohan Grading System was more useful in distinguishing glioblastoma multiforme and malignant astrocytoma in terms of prognosis than was the Nelson criterion of tumor necrosis. Glioblastoma multiforme (IV) patients had survivals of 44% at 1 year, 26% at 2 years, 4% at 5 years, and 0% at 10 years. Malignant astrocytoma (III) patients had 74% survival at 1 year, 56% at 2 years, 36% at 5 years, and 32% at 10 years, (all P less than 0.05). The tumor dose and tumor location affected survival significantly. Patients with hemispheric malignant astrocytoma who received 54-60 Gy had a 60% 5-year survival rate compared to 14% for doses of 35-50 Gy. Glioblastoma multiforme patients with noncentral tumors had a 9% 5- year survival with 54-60 Gy versus 0% with 35-50 Gy. Cerebral and cerebellar hemispheric tumors did better than central tumors. There were no 5-year survivors among patients with central tumors. Noncentral tumors, on the other hand, resulted in a 44% 5-year survival for malignant astrocytoma and 5% for glioblastoma multiforme. Radiation therapy was well tolerated during the acute period. Only one patient developed a late neurologic deficit attributable to therapy. The patient had hearing loss after two courses of 50 Gy each to a temporal lobe tumor. However, six of the 11 patients who survived for 5 years or longer had intellectual, emotional, or endocrine dysfunction.

Antineoplastic Combined Chemotherapy Protocols↗

Characterization of ATP-stimulated guanylate cyclase activation in rat lung membranes.

Many of the effects of ANP are mediated through the elevation of cellular cGMP levels by the activation of particulate guanylate cyclase. While the stimulation of this enzyme is receptor-mediated, the molecular mechanism of activation remains unknown. In this study we present evidence that ATP as well as its analogues adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S) and adenylylimidophosphate (AMPPNP) activates guanylate cyclase from rat lung membranes and markedly potentiates the effect of ANP on the enzyme. The order of potency is ATP gamma S greater than ATP greater than AMPPNP. The enzyme activation by adenine nucleotide and ANP together is much more than the sum of the individual activations, suggesting that ATP may be the physiological component essential for the ANP-stimulated guanylate cyclase activation. The ATP gamma S-stimulated guanylate cyclase activity diminishes in the presence of various kinds of detergents, suggesting either that the conformation of an ATP binding site in guanylate cyclase is altered by detergents or that protein-protein interaction may be involved in the activation of guanylate cyclase by ATP. Guanylate cyclase from rat lung membranes is poorly activated by ANP and/or ATP gamma S after removing the cytosolic and weakly membrane-associated proteins or factors by centrifugation. Pre-incubation of the membranes with ATP gamma S retains enzyme activation after membrane washing. These results suggest either that ATP gamma S stabilizes the conformation of nucleotide binding site in guanylate cyclase from denaturation by membrane washing, or that the stimulatory effect of ATP on guanylate cyclase activity may be mediated by accessory proteins or non-protein cofactors which are lost during membrane washing, but remain bound to membranes by ATP gamma S pretreatment.

Adenosine Triphosphate↗

Mechanism of cyclic GMP inhibition of inositol phosphate formation in rat aorta segments and cultured bovine aortic smooth muscle cells.

In order to clarify the mechanism(s) by which cyclic GMP inhibits the generation of inositol phosphates in rat aorta segments and cultured bovine aortic smooth muscle cells, we studied phosphoinositide hydrolysis and GTPase activity in homogenates and membrane preparations of cultured bovine aortic smooth muscle cells. Pretreatment of homogenate preparations with cyclic GMP plus ATP did not inhibit [8-arginine, 3H] vasopressin (AVP) binding, but resulted in a total suppression of the AVP-induced GTPase activation. The pretreatment with cyclic GMP and ATP also inhibited the formation of inositol phosphates induced by AVP in the presence of low concentrations of guanosine 5'-(gamma-thio)triphosphate (GTP gamma S), or by high concentrations of GTP gamma S alone. However, the formation of inositol phosphates by high concentrations of Ca2+ alone was not blocked. These results suggest that the ability of cyclic GMP to inhibit phosphoinositide hydrolysis results from an inhibition of a guanine nucleotide regulatory protein activation, and the interaction between guanine nucleotide regulatory protein and phospholipase C. While the precise site of this inhibition is not presently known, the inhibition by cyclic GMP is dependent upon the addition of ATP and probably entails a phosphorylation event since adenylylimidodiphosphate can not substitute for the ATP requirement.

Adenosine Triphosphate↗

Surgical cure of automatic atrial tachycardia by partial left atrial isolation.

Partial left atrial isolation was performed in a 16-year-old girl with persistent atrial tachycardia refractory to antiarrhythmic agents for 3 years. Intraoperative atrial epicardial and endocardial mapping showed that the earliest atrial activation occurred in an area lateral to the junction of the right superior pulmonary vein and the left atrium. An incision isolating the right half of the left atrial body containing the area of the earliest atrial activation and both right pulmonary veins from the remainder of the left atrium was made. The incision was then reapproximated. An excision encircling the interatrial septum containing the upper anterior portion of the septum with early activation was also made, and the atrial septal defect was repaired with a pericardial patch. The patient has been in sinus rhythm and free of arrhythmia for a follow-up period of 12 months.

Adolescent↗

Revised amino acid sequences of the three major phospholipases A2 from Bungarus fasciatus (banded krait) venom.

The structures of three cardiotoxin-like proteins obtained from the venom of Bungarus fasciatus (banded krait) were elucidated previously (Lu and Lo, 1980, 1981). Since their molecular sizes are similar to that of phospholipase A2 and since they show weak phospholipase A2 activities (Chang et al., 1983), a further study of their primary structures was carried out. Fractions Va, Vb-2 and VI, corresponding to the former V-2, V-3 and VI were determined to be typical phospholipases A2. Among 118 amino acid residues, they all have in common a Pro29 between Gly28 and Gly30, the latter two residues being implicated in Ca2+ binding together with Tyr26 and Asp47.

Amino Acid Sequence↗

Accelerated fractionation radiation therapy for liver metastases: selection of an optimal patient population for the evaluation of late hepatic injury in RTOG studies.

The palliation of hepatic metastases represents a major therapeutic problem in oncology. The generally unfavorable prognosis of patients with liver metastasis may complicate the evaluation of the efficacy and toxicity of various therapeutic modalities. The Radiation Therapy Oncology Group (RTOG) is evaluating new accelerated fractionation schemes for hepatic irradiation. In designing this study it became necessary to identify a favorable subpopulation of patients with an expected median survival of 6 months in whom the late effects of treatment could be evaluated. Data from two RTOG liver metastases studies (7605 and 8003) were analyzed using multi-variate techniques. Cases with a serum bilirubin level of greater than 1.5 mg%, performance score of less than 50, and gastric or pancreatic primary carcinomas were initially excluded because of the adverse influence of these factors on survival. One hundred and ninety cases met the criteria for inclusion in this analysis. A loglinear model was used to identify the patient characteristics associated with a favorable prognosis for survival. These included a performance score of 80-100, colorectal carcinoma primary, and no extrahepatic metastases. A logistic regression equation was derived and confirmed that the probability of surviving at least 6 months depended on the effects of performance score, primary site and the presence or absence of extra-hepatic metastases. Patients with all three favorable factors constituted 30% of the evaluable study population and had a predicted survival of 50% at 6 months. A patient population with these characteristics will be used to study the late effects of accelerated fractionated radiation therapy on the liver.

Breast Neoplasms↗

Developmental sequelae of fixed-rate ventricular pacing in the immature canine heart: an electrophysiologic, hemodynamic, and histopathologic evaluation.

Permanent, fixed-rate ventricular pacing (VVI) is associated with hemodynamic deterioration in the adult with compromised myocardial function. The effects of this pacing mode on the intact, immature heart, however, are largely unknown. Twelve beagle puppies (age 3 to 4 months) were equally divided into paced and age-matched control groups. All underwent identical hemodynamic and electrophysiologic evaluations. Transepicardial atrioventricular block and pacemaker insertion were additionally carried out in the paced group. After 4 months of observation, repeat hemodynamic and electrophysiologic measurements followed by histopathologic examinations were done in all puppies. The paced group exhibited significant (p less than 0.05) elevations of right atrial and pulmonary artery pressures, alterations in sinus node function, and prolongation of ventricular refractory periods compared with the control group. Initiation of dysrhythmias by programmed electrical stimulation was observed only among the paced group of puppies. Histologic examination demonstrated myofibrillar cellular disarray, dystrophic calcifications, prominent subendocardial Purkinje cells, and an increase in variable-sized, disorganized mitochondria only in the paced specimens. These findings indicate that permanent, apically-initiated VVI pacing ultimately predisposes to adverse cellular changes associated with hemodynamic and electrophysiologic deterioration in the intact, developing immature canine heart.

Animals↗

Proximal tubular epithelial cells possess a novel 42-kilodalton guanine nucleotide-binding regulatory protein.

The proximal tubule of the kidney represents an important location where adenylate cyclase regulates salt and water transport; yet a detailed characterization of the distribution and classification of guanine nucleotide-binding protein (G protein) and adenylate cyclase is lacking. We used purified brush border (20-fold) and basolateral membranes (14-fold) to characterize parathyroid hormone- and G protein-regulated adenylate cyclase and G-protein distribution. Adenylate cyclase was predominantly localized to basolateral membranes, while the 46-kDa alpha subunit of the stimulatory G protein (Gs) was 2-fold higher in brush border membranes than in basolateral membranes. The alpha subunit of the inhibitory G protein (Gi; 41 kDa) was equally distributed on immunoblotting but was 2-fold higher in brush border membranes than in basolateral membranes on radiolabeling with pertussis toxin. A 42-kDa cholera toxin substrate that cross-reacted with antisera to the common alpha subunit of G proteins and to Gs on immunoblotting and that was not immunoprecipitated with two Gi antisera was the most abundant alpha subunit and comprised approximately 1% of the total membrane proteins. These observations suggest that G proteins are important regulators of proximal tubular transport independent of adenylate cyclase.

Adenosine Diphosphate Ribose↗

Testing the procedure of simulated annealing by refining homologous immunoglobulin light-chain dimers.

The refinement of antigen-binding fragment structures by the method of simulated annealing was tested. Using the program X-PLOR, we refined the structure of one immunoglobulin light-chain dimer against 2.8 A diffraction data collected for a homologous light-chain dimer. The refinement proceeded smoothly; alpha-carbons of the conserved segments of the domain moved to the positions in the reference structure solved independently. An average movement of approximately 1.5 A for atoms in the variable domains (half of the molecule) was observed. Though the final R-factors and energy terms of the reference and test structures were very similar, some of the chain segments of the hypervariable loops (HVR3s) and the ends of some side chains did not converge to the positions in the reference structure. Therefore, although globally the refinement worked very well, positions of the loops and the side chains that are critical for immunoglobulin function have to be carefully examined by difference Fourier techniques.

Computer Simulation↗

Microvascular free muscle flaps for chronic empyema with bronchopleural fistula when the major local muscles have been divided--one-stage operation with primary wound closure.

It should be emphasized that most cases of chest empyema can be successfully treated with conventional thoracic surgery procedures. For chronic empyema with a bronchopleural fistula complicated by previous division of major local muscles following repeated thoracotomies, free muscle flaps are employed. Five such cases treated with this method resulted in successful closure of the airway fistula, as well as complete obliteration of the empyema cavity in a single operation. This method is very effective in eradicating infection and achieves prompt wound healing, decreased morbidity, and gradual improvement of pulmonary function after surgery. Analysis of roentgen ray and computed tomographic scans before and after surgery shows lung expansion when the transferred muscles atrophy. The results are satisfactory. The method described here is not the only solution to this problem, but it is a new approach that has advantages not seen in conventional methods. It is indicated only in patients who have been operated on many times and who have no remaining available local muscles.

Adult↗

Adenomatous polyp in a four-year-old child.

A 4-year-old white boy presented with rectal bleeding. An isolated polyp was removed and on histology was found to be adenomatous in nature. Family history was remarkable for polyposis with combined adenomatous and juvenile features. Variable expression of the syndrome was seen in various family members.

Adenoma↗

Efficient transformation of chicken embryo fibroblasts by c-Jun requires structural modification in coding and noncoding sequences.

To assess the transforming capability of the c-Jun protein, we introduced the chicken c-jun proto-oncogene into a replication competent avian retroviral expression vector (RCAS). Viral Jun efficiently transformed chicken embryo fibroblasts (CEFs) when expressed from this vector. Overexpression of c-Jun leads to transformation of CEFs with an efficiency that is 15- to 25-fold less than that seen for v-Jun, suggesting that v-Jun contains structural features that increase its oncogenic potential relative to c-Jun. There are four structural differences between v-Jun and c-Jun. To determine the relative contribution that each of these structural differences between v-Jun and c-Jun has on oncogenic activity, several deletion and substitution mutants were constructed. Each of these mutants was expressed in CEF and assayed for transformation by focus formation. Analysis of the results reveals that deletion of a region of 27 amino acids near the amino terminus of c-Jun and deletion of 3'-untranslated sequences are critical in activating the full oncogenic potential of Jun.

Amino Acid Sequence↗

Detection and identification of Mycobacterium tuberculosis by DNA amplification.

The polymerase chain reaction (PCR) was used to identify mycobacterial DNA sequences in uncultured clinical specimens. Two oligonucleotide primers derived from the sequence of a gene that codes for the 65-kilodalton antigen of Mycobacterium tuberculosis amplified DNA from all 11 species of mycobacteria tested. Amplified DNAs of nontuberculosis mycobacteria were found to be approximately 20 to 40 bases shorter than those from M. tuberculosis and Mycobacterium bovis BCG. DNA equivalent to that present in as few as 40 M. tuberculosis cells either alone or in the presence of DNA equivalent to that in 10(6) human cells could be detected. Results from analysis of cultured bacteria and clinical specimens showed PCR was sensitive and specific both in detecting mycobacteria and in differentiating M. tuberculosis and BCG from other species of mycobacteria. The PCR method with the primers reported here may become a useful tool in the early and rapid detection of mycobacterial infections in uncultured clinical specimens.

Base Sequence↗

The pharmacological and pathological studies on Taiwan folk medicine (IV): The effects of echinops grijisii and e. Latifolius.

The protective effect of "San-fang-feng" derived from the root of Echinops grijsii Hance on CCl4-induced hepatotoxicity has been studied. This crude drug was found to possess a marked hepatoprotective effect. A comparison of the protective effect with "Lou-lu" derived from the root of E. latifolius Tausch and "Pei-chai-hu" original Bupleurum chinense showed that E. grijisii and E. latifolius were more effective than B. chinense as reported previously. The results suggested that both E. grijisii and E. latifolius could correct the hepatocyte necrosis and functional disorder induced by the CCl4 treatment.

Alanine Transaminase↗

Figure-eight kinking of the aorta (pseudocoarctation) coexistent with coarctation.

An asymptomatic young man presented with a cardiac murmur and hypertension only in the right arm. Angiograms showed kinking of the aortic arch with a figure-eight appearance consistent with pseudocoarctation. Before the kinked segment, also demonstrated were a stenotic lesion in the aortic arch proximal to the left carotid artery and profound collateral circulations in the right thorax. These findings strongly suggested a rare combination of pseudocoarctation and true coarctation. His hypertension was corrected following surgery with a bypass graft between the ascending aorta and the abdominal aorta.

Adult↗