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Biomedical subjects

C H Chang

Publications and source records attributed to C H Chang.

At least 577 records · Page 32Linked to original sources

Quantitative evaluation of the extent of hepatic enzyme changes in Reye syndrome compared with normal liver or with non-Reye liver disorders: objective criteria for animal models.

Five enzymes were measured in 50 liver specimens (18 normal liver, 20 Reye liver, 12 diverse liver disorders other than Reye syndrome). The enzymes were: glutamic dehydrogenase (E.C. 1.4.1.3), monoamine oxidase (E.C. 1.4.3.4), lactate dehydrogenase (E.C. 1.1.1.27), D-glucose-6-phosphate dehydrogenase (E.C. 1.1.1.49), catalase (E.C. 1.11.1.6). The Reye syndrome group showed significant decreases in glutamic dehydrogenase (56%) and monoamine oxidase (70%) compared to normal control tissue and these changes were not characteristic of the non-Reye liver disorder group as a whole. Neither catalase nor lactate dehydrogenase appeared to be altered significantly in the Reye or in the abnormal control group compared with normal controls. Thus, only the prominent decreases in the mitochondrial enzyme activities appeared to be highly characteristic of Reye syndrome. Paradoxically, the means of the five hepatic enzymes and the admission levels of two serum enzymes indicative of liver damage (alanine and aspartate aminotransferase) were remarkably similar for both survivors and nonsurvivors of Reye syndrome.

Adolescent↗

Pulmonary function and ventilatory response to chemical stimuli in familial myopathy.

We studied the pulmonary function and ventilatory response to carbon dioxide and hypoxia in three sisters aged 16, 13, and 10 years who presented with droopy eyelids, external ophthalmoplegia, hearing loss, speech difficulty, and truncal muscular weakness. Pulmonary function test results showed decreased maximum static pressure, reduced vital capacity and total lung capacity, normal functional residual capacity, elevated residual volume, and reduced dynamic pulmonary volumes. The degree of functional abnormality paralleled the severity of clinical manifestations. The characteristic picture of pulmonary functional abnormality was distinct from either restrictive disorders of pulmonary origin or obstructive pulmonary diseases. The ventilatory response to hypoxia was markedly diminished and hypercapnic response was moderately diminished in all three patients.

Adolescent↗

Effects of adenosine on transmembrane potential and sarcolemmal Na+-K+ ATPase activity of human atrial myocardium.

Adenosine effects on the transmembrane potential characteristics and the sarcolemmal Na+-K+ ATPase activity of human atrial myocardium were studied in tissue from 20 patients who were divided into 2 groups based on the maximum diastolic potentials (MDP) greater than or less than -60 mV. Group A consisted of 10 patients with MDP of 70.84 +/- 4.20 mV and Na+-K+ ATPase activity of 15.37 +/- 0.46 mumole Pi/mg/hr. Ten patients with MDP of 44.54 +/- 6.24 mV and Na+-K+ ATPase activity of 12.55 +/- 0.42 mumole Pi/mg/hr were included in group B. Adenosine had no effects on the electrophysiological properties and the sarcolemmal Na+-K+ ATPase activity of atrial myocardium at concentrations below 1 X 10(-5) M in either group. Adenosine resulted in mildly altered atrial transmembranes potentials without significant effect on Na+-K+ ATPase activity at concentrations between 1 X 10(-5) M and 5 X 10(-4) M. However, a significant reduction of transmembrane potentials and an apparent inhibition of Na+-K+ ATPase activity were observed only in tissue from group B. These results suggest that: 1) adenosine has no effect on the electrophysiological properties and the sarcolemmal Na+-K+ ATPase activity of human atrial myocardium at physiological concentrations; 2) adenosine induced inhibition of the sarcolemmal Na+-K+ ATPase activity in slow channel-dependent atrial tissues may be a mechanism responsible for the alterations of transmembrane potentials under unphysiological conditions; and 3) adenosine contributes to the genesis of cardiac arrhythmias during acute myocardial ischemia, which can reduce transmembrane potentials of the myocardial cells and may increase the myocardial adenosine level above its effective concentration.

Action Potentials↗

Morphologic grading of hepatic mitochondrial alteration in Reye's syndrome: potential prognostic implication.

Mitochondrial alterations are known to be constantly associated with Reye's syndrome. Fifty-eight liver specimens from 50 patients who fulfilled the clinical and pathologic criteria were examined by electron microscopy. The degree of mitochondrial injury was graded I, II, and III according to the severity of the alteration of mitochondrial matrix. The results correlated well with clinical parameters--specifically initial clinical stage, peak clinical stage, and clinical outcome. Electron microscopic examination of hepatic mitochondria is therefore potentially useful in evaluating Reye's syndrome patients.

Biopsy↗

Necrotizing lymphoid vasculitis in X-linked lymphoproliferative syndrome.

An 8-year-old maternally related relative of three boys who had developed agammaglobulinemia associated with Epstein-Barr virus (EBV)-induced infectious mononucleosis was studied for X-linked lymphoproliferative syndrome (XLP) in 1979. At that time, he demonstrated no striking immunologic aberrations and was seronegative for EBV. Subsequently, immunologic abnormalities including failure to switch from IgM to IgG antibody synthesis after secondary immunization with bacteriophage phi X174 were detected. In 1983, he experienced episodic intracerebral hemorrhages, with the second being fatal. At autopsy, necrotizing vasculitis and aneurysms involving arteries of the central nervous system were observed. Studies of blood obtained immediately before and after death failed to show antibodies to EBV. However, EBV genome was demonstrated in tissues obtained at autopsy by DNA hybridization studies. Fatal lymphoid vasculitis in this patient is unique among boys with XLP in the registry. These findings probably extend the phenotypic expressions of XLP.

Antibodies, Viral↗

Multiple primary tumors in association with prostatic cancer.

One hundred forty-six patients with clinically nonmetastatic carcinoma of the prostate were treated at Columbia-Presbyterian Medical Center from 1964 through 1976. Of these 146 patients, 24 (16.4%) had developed at least one additional primary cancer. This review contrasts the 122 patients who had a single primary prostate cancer only with the 24 patients who had additional primary carcinomas with respect to age, racial distribution, clinical stage, and prostate cancer histology including Gleason's score, patterns of failure of prostate cancer, and survival data. Local failure and distant failure were less in the multiple primary group. Patients with high Gleason's scores appear to be at greater risk for second primaries. Five-year observed survival (by actuarial life table method) for the single prostate primary group was 76.5%, and 5-year observed survival of the prostate multiple primary group where prostate cancer appeared first was 71%.

Adult↗

Affinity labeling of the androgen receptor in rat prostate cytosol with 17 beta-[(bromoacetyl)oxy]-5 alpha-androstan-3-one.

An androgen affinity label, 17 beta-[(bromoacetyl)-oxy]-5 alpha-androstan-3-one, has been synthesized in both radioactive and nonradioactive forms. The affinity label (170 Ci/mmol) was characterized and found to have a high degree of purity. Affinity labeling of the androgen receptor from rat ventral prostate was androgen specific and appeared to be directed at the steroid binding site of the protein. Covalent binding was achieved at 0 degrees C; however, heat treatment at 23 degrees C for 30 min enhanced covalent binding by 31%. The covalently bound steroid was resistant to extraction with organic solvents and precipitation with trichloracetate. The Stokes radius (4.2 nm) and sedimentation coefficient (4.5 S) were identical with those found for receptor bound noncovalently to dihydrotestosterone. Gel electrophoresis of the affinity-labeled receptor under denaturing conditions revealed a molecular weight of 86000. The same molecular weight was observed for the receptor from rat seminal vesicle. This affinity label will be useful in future studies on the structure and function of androgen receptors.

Affinity Labels↗

Cloning and delimiting one chloroplast DNA replicative origin of Chlamydomonas.

The EcoR1 restriction fragments containing D-loops which marked the replication origin of chloroplast DNA were identified in two different species of Chlamydomonas. Each fragment was cloned in the E. coli plasmid pBR325. The cloned fragments were compared by restriction endonuclease analyses and by heteroduplex analyses in the electron microscope. The relative position of the D-loop regions and the homologous regions between the 2 fragments was determined. The D-loops were located within one short homologous region of 0. 42kb in length between the 2 cloned restriction fragments. The homologous region was subcloned in pBR322. Closed circular plasmid DNAs containing the short homologous region showed preferred denaturation in the D-loop region under physiological salt concentration which suggested that D-loop region was AT rich. Sequence divergence was detected at both ends of the D-loop region. Southern blot analyses indicated the presence of species-specific repetitive sequences within the divergent regions.

Base Sequence↗

Cobalt-bleomycins and deoxyribonucleic acid: sequence-dependent interactions, action spectrum for nicking, and indifference to oxygen.

Light-induced strand scission of DNA by cobalt-bleomycins is more likely to occur at certain base sequences than others. By use of 32P-end-labeled DNA restriction fragments as the substrates for cleavage, products have been analyzed on high-resolution polyacrylamide gels and compared to those produced by iron-bleomycin. The results indicate that the sites of damage to DNA are similar in both cases: pyrimidine residues located at the 3' side of a guanine are preferentially attacked. Consistent with the observed nicking specificity, interactions between cobalt-bleomycin and guanine residues in the trinucleotide sequence GGT are revealed in a dimethyl sulfate methylation experiment. The action spectrum for the light-induced DNA cleavage reaction correlates with the absorption spectrum of cobalt-bleomycin in the wavelength range between 330 and 450 nm. In contrast to iron-bleomycin, the extent of DNA degradation by light-activated cobalt-bleomycins appears to be indifferent to the concentration of dissolved oxygen in the reaction medium, and little or no base propenal is produced. Bases (e.g., thymine) are released by both agents. Fluorescence quenching experiments show that apparent binding constants of cobalt-bleomycin complexes with DNA are in the 10(7) M-1 range in 25 mM tris(hydroxymethyl)aminomethane, pH 8, 1 mM NaCl, and 1 mM ethylenediaminetetraacetic acid at 25 degrees C.

Animals↗

A family study of renal dysplasia.

A family study was undertaken to investigate genetic involvement in renal dysplasia, which is defined as abnormal metanephric differentiation. Probands were ascertained through the retrospective examination of necropsy records and the reevaluation of available material, which included microscopic examinations of the kidneys, gross descriptions of organs, and gross photographs. We obtained family histories and performed physical examinations and renal ultrasonography on parents and sibs of the 21 probands. In only one family a sibling with renal dysplasia was discovered; both the proband and the previous stillborn sib had renal dysplasia in association with posterior urethral values. Renal dysplasia could have resulted from urinary tract obstruction secondary to the urethral valves, with inheritance of the valves as the primary abnormality. However, we cannot exclude primary inheritance of the renal abnormality, perhaps with multifactorial determination with a threshold. The empiric recurrence risk of 2.1%, calculated from this family study, was statistically not significantly different from zero. We can assume, therefore, that the multicystic and aplastic types of renal dysplasia, which predominated in this study, are sporadic or rarely familial, but certain other types of renal dysplasia, identified in the literature as familial, probably carry a higher recurrence risk.

Abnormalities, Multiple↗

Physicochemical characterization of the androgen receptor from hyperplastic human prostate.

In this manuscript we have characterized the androgen receptor from human benign prostatic hypertrophied (BPH) tissue. BPH tissue was obtained fresh from surgery, ground, and frozen in liquid nitrogen. Tissue was homogenized in 10 mM Tes buffer (pH 7.4 at 25 degrees C) containing 0.25 M sucrose, 20 mM Na2MoO4, 12 mM monothioglycerol, and 1.5 mM EDTA. Cytosol was labeled with (3H)-R1881 (0.5-10 nM) +/- a 100-fold excess of R1881 and a 500-fold excess of triamcinolone acetonide to identify specific androgen receptor sites. An exchange assay was developed, whereby maximum binding was achieved by raising the temperature to 30 degrees C for 15 min. A high-affinity binding protein was detected (Kd = 1.3 +/- 0.8 nM) which had a binding capacity of 15 +/- 7 fmol/mg protein. Binding was specific for androgens with the following Ki (nM) values: R1881 (0.09), dihydrotestosterone (6), testosterone (50), progesterone (92), estradiol (100), epitestosterone (860), and cortisol (greater than 1,000). Under high ionic conditions the sedimentation coefficient of the receptor was 4.1 S. Higher S values were not observed in the presence of the following protein inhibitors: leupeptin (20 or 150 microM), iodoacetamide (10 mM), DFP (5 mM), PMSF (1 mM), bacitracin (0.1 mM), antipain (0.1 mM), aprotinin (1 TIU/ml). Gel filtration analysis revealed a Stokes radius of 6.5 nm. These data indicate a Mr of 120,000 and a f/fo of 2.01. The receptor eluted from a chromatofocusing column at a pH of 6.8. The receptor bound to phosphocellulose and DNA cellulose after being heat-treated for 15 min at 30 degrees C. These results suggest that BPH tissue contains an androgen receptor which is similar to receptors in other androgen-responsive tissues.

Binding, Competitive↗

Neuropathologic findings in thanatophoric dysplasia.

Neuropathologic study of eight cases of thanatophoric dysplasia (dwarfism) reveals developmental abnormalities including hypoplasia of posterior fossa, megalencephaly, cerebral gyral disorganization, hippocampal malformation, neuronal heterotopia, nuclear dysplasia, and abnormal axonal bundles. There are no noticeable differences in CNS abnormalities between thanatophoric dysplasia with and without cloverleaf skull (Kleeblattschädel). The CNS abnormalities, likely the result of abnormal neuronal migration and cytoarchitectonic disarrangement, are apparently not caused by skeletal abnormalities. The observation suggests that CNS abnormalities represent a characteristic and distinct manifestation of thanatophoric dysplasia.

Basal Ganglia↗

Exchange assay for androgen receptors in the presence of molybdate.

Several reports have shown that sodium molybdate stabilizes steroid hormone receptors. We have utilized these observations to develop an exchange assay for the androgen receptor at elevated temperatures. Exchange was found to be complete after 30 min at 30 degrees C. Receptor degradation was negligible during this treatment. Scatchard analysis indicated that the dissociation constant of the androgen receptor was similar both in the absence (Kd = 3.9 nM) and presence (Kd = 2.9 nM) of molybdate. Steroid specificity of the androgen receptor was unaltered by this treatment. The exchange procedure was reproducible, with an interassay variation of 2.45% and intraassay variation less than 10.0%. Using this assay, highest concentrations of androgen binding were measured in androgen target tissues of the rat (Dunning R3327 tumor, prostate and seminal vesicle; 23.37, 20.20 and 19.84 fmol/mg protein respectively). Lower concentrations were observed in other tissues (lung, brain, heart, spleen, liver and kidney; 9.06, 5.63, 3.50, 2.42, 2.33 and 1.36 fmol/mg protein respectively). These results demonstrate that molybdate stabilization of the androgen receptor allows efficient steroid exchange without significant alteration of the receptor's steroid binding properties. Furthermore, this exchange assay can be used to obtain a reasonable measurement of receptor concentrations in different androgen target tissues.

Animals↗