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Biomedical subjects

C M Chang

Publications and source records attributed to C M Chang.

At least 19 recordsLinked to original sources
PubMed1992

Pseudomonas exotoxin A-epidermal growth factor (EGF) mutant chimeric protein as an indicator for identifying amino acid residues important in EGF-receptor interaction.

Epidermal growth factor (EGF) was fused to the carboxyl end of a modified pseudomonas exotoxin A that has its toxin binding domain deleted. This chimeric toxin designated as PE(delta Ia)-EGF kills A431 cells through the EGF receptor-mediated pathway. In this study, we used a random mutagenesis approach to make point mutations on EGF, followed by replacing the wild type EGF in PE(delta Ia)-EGF with these EGF mutants. We have constructed 14 different PE(delta Ia)-EGFmutants, and examined their EGF receptor binding activity as well as their cytotoxicity to A431 cells. Our results showed that individual mutations of Val19 to Glu and Val34 to Asp in the EGF domain of PE(delta Ia)-EGFmutants resulted in an increase in the binding affinity to EGF receptor and cytotoxicity to A431 cells. On the other hand, individual mutations of His16 to Asp and Gly18 to Ala in the EGF domain of PE(delta Ia)-EGFmutants lead to a decrease in the binding affinity to EGF receptor and cytotoxicity to A431 cells. In addition, mutations of any of the cysteine residues of EGF in PE(delta Ia)-EGFmutants resulted in the loss of their binding activity to EGF receptor and a corresponding loss of their cytotoxicity. This study indicates that the cytotoxicity of PE(delta Ia)-EGFmutant to EGF receptor-bearing cells may be used as an indicator to screen mutations of EGF important in EGF-receptor interactions.

ADP Ribose Transferases↗
PubMed1992

Treatment of idiopathic hemifacial spasm with botulinum toxin.

Twelve patients with idiopathic hemifacial spasm received treatment with botulinum toxin A over a period of 18 months. Of 76 treatments given, most (94.7%) led to successful relief of eyelid spasms and all treatments were successful for perioral and lower facial muscle spasms. An average dose of 9.3 units of toxin per session was given to produce a mean interval of relief of 10.8 weeks. Blepharoptosis was the only ocular side effect; it was mild, reversible and occurred in 2 patients. However, lower facial palsy was frequent (9 patients); it was mild to moderate in severity but only partially reversible in 8 patients. Dosage for lower facial muscles should therefore be reduced.

Adult↗
PubMed1992

Vascular pseudoparkinsonism.

Vascular pseudoparkinsonism may be confused with idiopathic Parkinson's disease. Patients may be unnecessarily treated with anti-parkinsonian drugs while their underlying vascular disease is ignored. We investigated 250 parkinsonian patients seen in our Movement Disorders Clinic for a possible vascular etiology. After excluding those with a known secondary cause such as drug-induced parkinsonism, progressive supranuclear palsy, multiple system atrophy and hyperparathyroidism, brain computed tomography and/or magnetic resonance imaging were performed on those who showed poor or no response to levodopa. In those with an ischemic lesion demonstrated on neuroimaging, anti-parkinsonian drugs were stopped and the patients were reassessed. Eleven patients (4.4%) had ischemic brain lesions accounting for their parkinsonism. All were initially diagnosed as Parkinson's disease because of the prominence of bradykinesia and rigidity. Gait disturbance was also common, but resting tremor was distinctly absent. Three anatomical patterns with different prognosis were identified. Three patients with basal ganglia lacunar infarct recovered spontaneously, three with frontal lobe infarcts remained static and five with periventricular and deep subcortical white matter lesions had progressive deterioration. Autopsy in one patient confirmed bilateral frontal lobe watershed infarcts and the absence of brain stem Lewy bodies. Parkinsonian patients with poor or no response to levodopa therapy should be investigated for a vascular etiology.

Aged↗
PubMed1992

Huntington's disease in Chinese: a hypothesis of its origin.

The period prevalence (1984-91) of Huntington's disease (HD) in Hong Kong Chinese was 3.7 per million population. HD patients in Mainland China and Hong Kong showed similar hereditary pattern, clinical and pathological features as in the West. Chinese HD patients were male predominant with a younger age of onset and death. Their ancestral origin could be traced mostly to the coastal provinces of China. It is proposed that Chinese HD patients may have a European origin and share the same gene pool as their white counterparts.

China↗
PubMed1992

Postinfectious myelitis, encephalitis and encephalomyelitis.

Six cases of post-infectious encephalomyelitis are described. A preceding non-specific viral-like illness occurred 4 to 20 days before the onset of the neurological deficits. The clinical syndromes included transverse myelitis, focal encephalitis and encephalomyelitis (each in one case) and diffuse encephalitis in 3. Magnetic resonance imaging appeared to be the investigation of choice. High dose corticosteroids were given to 4 patients who recovered partially or fully. The patient with focal encephalitis had a spontaneous and complete recovery. The remaining patient with diffuse encephalitis died 3 days after the onset; autopsy showed prominent lymphocytic perivascular cuffing in the white matter and lymphocytic infiltration of the meninges.

Adrenal Cortex Hormones↗
PubMed1979

Permeability factor contaminating hyaluronidase preparations.

Both crude and highly purified testicular hyaluronidase preparations have been shown to contain a component which increases the permeability of the microcirculation in rat skin. This permeability activity had an isoelectric point of 7.4 while hyaluronidase was 9.4. It also could be separated from hyaluronidase by acrylamide gel electrophoresis. The permeability factor was not inhibited by serum and may explain previous observations that hyaluronidase preparations decrease the ischemia and necrosis appropriate to experimental myocardial infarction in vivo.

Animals↗
PubMed1979

Macromolecular, anionic pulmonary permeability factor.

Aqueous extracts of fresh or acetone-powdered calf lung have been found to contain a factor which increases the permeability of the microcirculation when injected into the skin of rats. This permeability factor, which is not found in similar extracts of muscle or kidney, was concentrated by Amicon ultrafiltration at a molecular weight range of between 50,000 and 100,000 daltons and via isoelectric focusing at an IEP of pH 4.2. After preparative acrylamide gel electrophoresis, this permeability factor was homogeneous by electrophoretic criteria and in SDS acrylamide gel electrophoresis had a molecular weight of approximately 82,000 daltons. This apparently homogeneous permeability factor from lung was inhibited by pepstatin, and yet possessed no acid proteolytic activity against any substrate. Its activity was completely inhibited by pretreatment of the animals with antihistamines. This pepstatin-inhibitable permeability factor was found largely in the lysosomal fraction of fresh lung and could also be obtained by extraction of large amounts of alveolar "washout" macrophages. Since macrophages, during phagocytosis, are known to leak significant quantities of their lysosomal contents, the fact that one of these components is a material which could release histamine from mast cells and thereby increase locally the permeability of the microcirculation may be of importance in the defense system of the lung.

Animals↗
PubMed1979

Pulmonary macrophage growth factor.

Pulmonary macrophage growth factor (MCF) can be purified from the "used" serum-free medium of cultures of mouse lung cells by concentration and dialysis over a 30,000-dalton Amicon ultrafilter and subjecting the retentate to isoelectric focusing. This yields a protein fraction with an isolelectric point of pH 4.2, which contains all the MGF activity. Upon electrophoresis of this fraction in analytical gels, one large and four small bands could be visualized. All bands were biologically active. This same "heterogenous" fraction ran as one band (mol wt 68,000) in SDS analytical gel electrophoresis, suggesting the ordered aggregation of this monomer. This was confirmed by reelectrophoresis of the first (and largest) band demonstrating the same 5-banded pattern as the initial material.

Animals↗
PubMed1979

Normocholesterolemic dysbetalipoproteinemia with xanthomatosis.

A patient is described who has marked palmar xanthomatosis associated with a normal concentration of plasma cholesterol. Analysis of xanthomas revealed them to contain large quantities of cholesterol with both intra- and extracellular lipids. Examination of plasma lipoproteins showed them to be consistent with a pattern of dysbetalipoproteinemia (Type III hyperlipoproteinemia). VLDL had beta-mobility on electrophoresis, a high cholesterol/triglyceride ratio, and increased apoprotein B. However, arginine-rich apoprotein was not increased in VLDL, in contrast to hypercholesterolemic patients with the Type III pattern. Nevertheless, the E3 subfraction of the arginine-rich apoprotein was virtually absent, which is characteristic of dysbetalipoproteinemia. Cholesterol and bile acid synthesis were in the normal range. Thus, of particular interest was the development of severe xanthomatosis without hypercholesterolemia in this patient. Therefore, tissue accumulation of cholesterol was apparently the result of a qualitative abnormality in lipoproteins and not due to an excess of plasma cholesterol.

Adult↗
PubMed1978

Interactions of native and modified human low density lipoproteins with human skin fibroblasts.

125I-labeled low density lipoprotein (LDL) covalently bonded to Sepharose beads was not degraded by normal human fibroblasts nor did it trigger inhibition of sterol synthesis. The Sepharose beads loaded with LDL bound very tightly to the surface both of normal fibroblasts and fibroblasts from a subject with homozygous familial hypercholesterolemia; control Sepharose beads (activated sites covered with glycine) did not adhere to either cell type. LDL was extracted by a modification of the method of Gustafson (Gustafson, A. (1965) J. Lipid Res. 6, 512-517), so as to remove essentially all cholesterol, cholesterol ester and triglyceride. This modified LDL was bound, internalized and degraded as well as or better than native LDL. However, it failed to suppress sterol synthesis. These results provide additional evidence that the sterol moiety of the LDL is the key component affecting sterol synthesis. They also imply that the neutral lipids of LDL play a minor role in the binding of LDL to cell membranes and that the apoprotein rather than molecular size and shape is the critical factor.

Apolipoproteins↗
PubMed1978

The biochemistry of lymphocyte-derived mediators of immunological inflammation.

Evidence is presented to indicate that there exists in lymphoid tissue, as a result of transforming lymphocytes, a new lymphokine which is chemotactically specific for lymphocytes, called 'lymphotactin'. Lymphotactin has been purified to electrophoretic homogeneity; has a molecular weight of 10,500 D and an isoelectric point of 5.9. Its role in amplifying the immune defense system by recruitment of naive lymphocytes into propinquity with the challenging antigens is suggested. Purification of macrophage migration inhibitory factor from thymus extracts to electrophoretic homogeneity leads to a compound of molecular weight of 36,500 D and an IEP of 6.9. Chemically it contains sialic acid and o-methyl glucopyranoside as its only carbohydrates. Purified MIF activates the macrophage phagocytically. Skin reactive factor and lymph node permeability factor have been isolated and purified and are found to be inhibited by pepstatin and antihistamine and to have an isoelectric point of pH 4.2 and a molecular weight of 50,000--100,000 D. It is believed that this anionic permeability increasing agent actually arises from the lysosomes of macrophages and lymphoblasts (the normal small lymphocyte having essentially no lysosomal organelles). The mononuclear cell infiltration characteristic of crude SRF and LNPF may proceed from their being contaminated with lymphotactin.

Animals↗
PubMed1977

The purification and characterization of a lymphokine chemotactic for lymphocytes--lymphotactin.

Aqueous extracts of the thymus from vaccinated calves contain a protein specifically chemotactic for lymphocytes (lymphotactin). Lymphotactin has been isolated and purified by ethanol fractionation, ultrafiltration, isoelectric focusing, and preparative acrylamide gel electrophoresis. Its isoelectric point is 5.9, and the molecular weight by both SDS electrophoresis and exclusion chromatography is about 10,500. The purified sialoprotein is homogeneous at three different pH's in acrylamide gel electrophoresis. As little as 1 microgram of this material intraperitoneally wlll produce massive lymphocyte infiltration within 4 h in vivo.

Animals↗
PubMed1976

Relationship of structure to function in bacterial endotoxins: serologically cross-reactive components and their effect on protection of mice against some gram-negative infections.

Rabbit antisera were prepared against the heptoseless Re mutants, Salmonella minnesota R595 and S. typhimurium SLI102, as well as against purified R595 glycolipid coated on autologous erythrocytes. The antisera cross-reacted with the endotoxic glycolipids extracted from Re mutants of various bacterial strains, including S. minnesota R595, S. typhimurium SLI102, Escherichia coli D3Im4, E. coli D2If2 and E. coli F515, as shown by passive haemagglutination and gel diffusion tests. The anti-Re sera also cross-reacted with the RESI preparations (a purified 'lipid A' fraction) from the endotoxic lipopolysaccharides of various heterologous smooth Gram-negative bacteria including Serratia marcescens. Psuedomonas fluorescens and E. coli 0127. However, the same antisera failed to protect mice against infection by Gram-negative bacteria such as Klebsiella pneumoniae type II, S. typhi 0901, P. aeruginosa 119 and E. coli. The results suggest that although the lipid moieties of the lipopolysaccharides in the cell wall of Gram-negative bacteria share cross-reactive immunodeterminant groups, these groups may not be accessible to antibody against them.

Animals↗