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Biomedical subjects

C M Chang

Publications and source records attributed to C M Chang.

At least 73 records · Page 4Linked to original sources

Prognostic significance of human papillomavirus detected with polymerase chain reaction in cervical cancer.

In order to investigate the prognostic factors of cervical cancer and its association with human papillomavirus (HPV), we analyzed 50 specimens of cervical cancer with a DNA polymerase chain reaction (PCR) mainly to detect HPV types 16 (HPV 16) and 18 (HPV 18). The result showed that at least 74% (37/50) of the specimens had HPV DNA. Among them, 54% (20/37) of the cases were HPV 16 and 32% (12/37) were HPV 18. These HPV DNA positive patients had poorer differentiation in histology than the HPV DNA negative patients. We draw no conclusion about the prognostic significance of HPV DNA in cervical cancer. Perhaps more cases should be analyzed.

Adult↗

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↗

Hepatitis B virus replication in well differentiated mouse hepatocyte cell lines immortalized by plasmid DNA.

The primary hepatocytes cultured from adult BALB/c mice were readily transfected by plasmid DNA and could be immortalized at a frequency of approximately 0.1 to 0.6 x 10(-7) cells/micrograms of the transfected DNA. There was no detectable plasmid DNA at the tenth cell passages. A total of five mouse hepatocyte cell lines were established. Most of them were tumorigenic. Three of the established mouse hepatocyte cell lines were well differentiated, since they expressed liver-specific genes. Further transfection of these three well differentiated mouse hepatocyte cell lines with hepatitis B virus (HBV) DNA showed that the HBV-transfected cells had integrated HBV genomes, HBV-specific mRNA transcripts, and expression of hepatitis B surface and hepatitis B core antigens. One of the lines, ML-3Neo (HBV), even secreted HBV-like particles. Furthermore, circulating hepatitis B surface antigens were detected in the sera of BALB/c mice bearing ML-3Neo (HBV) tumors. These cell lines provide a convenient model for future studies on the host immune reaction against HBV and on the transformation of hepatocytes by HBV and other cellular oncogenes and the determination of their effects on hepatocellular differentiation.

Animals↗

Characterization of a cis element required for packaging and replication of the human hepatitis B virus.

The hepatitis B virus (HBV) is a DNA virus; however, it replicates through a pregenomic RNA intermediate. Several HBV-specific mRNAs are transcribed, but only the pregenomic RNA transcript is encapsidated. The encapsidation of the HBV genome, therefore, is a highly specific and selective process. Using mutational analyses and complementation tests, we have defined a 99-nucleotide cis element located at the pre-C/C region of the HBV genome which is essential for encapsidation and the replication. Furthermore, HBV genome truncated down to 1.5 kb and HBV mutants carrying foreign DNA inserts could still replicate in our complementation system.

Base Sequence↗

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↗

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↗

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↗

Treatment of acute cerebral hemorrhage with intravenous glycerol. A double-blind, placebo-controlled, randomized trial.

BACKGROUND AND PURPOSE: Hitherto, treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers. METHODS: We undertook a double-blind, stratified and randomized, placebo-controlled clinical trial. Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited, provided computed tomography confirmed hemorrhage and informed consent was obtained. After stratification into alert, semicoma, and coma subgroups using the Glasgow Coma Scale, 107 patients received active treatment (500 ml of 10% glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days) and 109 were given corresponding saline treatment. Using a variety of objective scoring systems, patients were followed up for up to 6 months. RESULTS: At follow-up, all measures of outcome in the treated and control groups were very similar. At 6 months, respective mortality rates were 37 of 107 and 33 of 109. Corresponding mean +/- SD improvements in Scandinavian Stroke Study Group scores were 8.35 +/- 16.9 versus 11.55 +/- 15.6 (long-term) and 0.64 +/- 7.3 versus 2.40 +/- 6.9 (prognostic), and improvements in the Barthel Index ratings were 10.72 +/- 24.7 versus 13.95 +/- 23.3, respectively. Glasgow Coma Scale score improvements in the survivors were 0.81 +/- 1.5 and 1.16 +/- 1.7 in the treated and control groups, respectively. Hemolysis (generally subclinical) was the only adverse effect of glycerol noted. CONCLUSIONS: In the absence of any clinically or statistically significant difference in outcome between the treated and control groups, this trial provides no justification for glycerol therapy following acute cerebral hemorrhage.

Acute Disease↗

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↗

Overexpression of epidermal growth factor and insulin-like growth factor-I receptors and autocrine stimulation in human esophageal carcinoma cells.

The growth-stimulatory effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and insulin-like growth factor-I (IGF-I) on the human esophageal carcinoma cell line CE48T/VGH were evaluated. Under serum-free conditions, EGF, TGF-alpha, and IGF-I promoted 3.6- to 4.1-fold increased cell proliferation. Scatchard analyses and Northern blot hybridization revealed that both the EGF/TGF-alpha receptor and the IGF-I receptor were overexpressed in CE48T/VGH cells. Furthermore, ligand-dependent autophosphorylation of the EGF receptor and the IGF-I receptor was clearly detected using antireceptor and antiphosphotyrosine antibodies. Autocrine regulation was strongly indicated by the following evidence: (a) CE48T/VGH cells were found to express TGF-alpha and IGF-I genes, (b) serum-free conditioned medium promoted the growth of CE48T/VGH cells and stimulated the autophosphorylation of the EGF/TGF-alpha receptor and the IGF-I receptor, and (c) the addition of IGF-I receptor antibodies significantly suppressed CE48T/VGH cell growth under serum-free conditions. Our studies suggest that the overexpression of EGF and IGF-I receptors and autocrine growth regulation may concertedly control the proliferation of esophageal carcinoma cells.

Animals↗

Immunological and ultrastructural studies of the nuclear coiled body with autoimmune antibodies.

Studies with human autoimmune sera identified auto-antibodies reacting with a novel antigen of 80 kDa. In interphase mammalian cells, the 80-kDa antigen was enriched in nuclear coiled bodies and was used as a marker for this nuclear structure. This antigen was subsequently named p80-coilin. By light and electron microscopic immunocytochemistry, a number of other antigens were also localized to the coiled body, including components of small nuclear ribonucleoproteins which are involved in the processing of nucleolar and extranucleolar RNA. Although the function of the coiled body is unknown, the presence of these subcellular particles might indicate an involvement in RNA metabolism. The identification of a protein highly enriched in this structure and the availability of specific antibodies might help in its isolation and the study of its function.

Animals↗

Herpes zoster associated encephalitis in dialysis patients.

Two patients on dialysis because of chronic renal failure who developed herpes zoster associated encephalitis are reported. Both developed overt encephalopathy despite treatment with oral acyclovir for the preceding herpes zoster eruption. The encephalopathy responded rapidly to intravenous acyclovir.

Acyclovir↗

Cerebral haemorrhage in anticoagulated patients with non-septic mechanical valvular prosthesis.

Cerebral haemorrhage in anticoagulated patients with mechanical valvular prosthesis poses an uncommon but difficult management problem. Four such patients are presented: one patient had delayed haemorrhagic transformation of a preexisting cerebral infarct, one probably had de novo haemorrhage complicating hypertension and in two patients cerebral haemorrhage was associated with excessive anticoagulation. Conservative management including the use of fresh frozen plasma, delayed heparinisation and warfarinisation was used. Both patients with anticoagulant overdose died as a result of extensive haemorrhage despite the drainage of cerebellar haematoma in one patient. The remaining two patients survived with minimal neurological deficits. Diagnosis of the underlying cause of cerebral haemorrhage, and the timing of heparinisation and anticoagulation are discussed.

Adult↗

Beta-adrenergic blockade in the prevention of myocardial infarction: a new theory.

Beta-adrenergic blockers have a protective effect in reducing mortality in survivors of myocardial infarction. It is proposed that, in addition to their effects in reducing heart rate, blood pressure, myocardial contractility and ventricular ectopy, beta-blockers may prevent or attenuate the fracture of vulnerable atherosclerotic plaques and thereby reduce coronary thrombosis, myocardial infarction and sudden cardiac death.

Adrenergic beta-Antagonists↗

A multimodal neurophysiological assessment in terminal renal failure.

A prospective multimodal neurophysiological study was conducted on 36 patients with end-stage renal failure, 16 of whom subsequently underwent renal transplantation (TR). Nerve conduction study and somatosensory evoked potentials revealed that peripheral conduction deficit, often subclinical, was the commonest abnormality, and TR resulted in substantial improvement. Visual evoked potentials demonstrated subclinical impairment, which did not improve after TR. The brainstem auditory evoked potentials were essentially normal and unaffected by TR.

Brain Stem↗