Biomedical subjects

C M Chang

Publications and source records attributed to C M Chang.

At least 55 records · Page 3Linked to original sources

PubMed1997

Sublethal gamma irradiation increases IL-1alpha, IL-6, and TNF-alpha mRNA levels in murine hematopoietic tissues.

The effects of sublethal (7.75 Gy) 60Co gamma radiation exposure on endogenous bone marrow and splenic interleukin-1alpha (IL-1alpha), IL-6, and tumor necrosis factor-alpha (TNF-alpha) mRNA and protein levels were assayed in B6D2F1 female mice. Bone marrow and spleen were harvested from normal and irradiated mice on days 2, 4, 7, 10, and 14 postexposure, and cytokine mRNA levels were determined by reverse transcription polymerase chain reaction (RT-PCR) and Southern blot analysis. IL-1alpha mRNA levels were significantly increased in bone marrow at days 2 and 4 postirradiation and at day 7 in spleen compared with controls. Postirradiation IL-6 mRNA levels showed a significant increase at day 2 in bone marrow and at days 7 and 10 in spleen. TNF-alpha mRNA levels exhibited a significant increase at day 2 postirradiation in bone marrow, but in spleen no difference between control and irradiated samples was observed on any day postirradiation. Interestingly, there were no significant differences in the cytokine protein levels in postirradiation bone marrow, spleen, or serum when compared with normal controls.

Animals↗

PubMed1997

Shelf life of unbuffered rapid urease test.

BACKGROUND: Unbuffered rapid urease test (RUT) is an accurate and inexpensive method to detect Helicobacter pylori. However, the test is not always readily available because the reagents must be mixed freshly or stored at -20 degrees C after mixing. From our experience, storage at 4 degrees C for less than 6 days seemed to have no effect on the test's accuracy. This prospective study was undertaken to evaluate the shelf life of our unbuffered RUT. MATERIAL AND METHODS: Forty-five patients were studied. From all patients, two sets of antral biopsy (X2) and body biopsy (X1) were taken. One set was subjected to histological examination; the other set was placed into a single capped Eppendorff tube for RUT. The tube was examined for any color change at 1 and 5 minutes. RESULTS: Twenty-six patients (58%) were infected as defined by histological examination. The reagent was classified according to the storage time (group 1, < or = 5 days; group 2, > 5 days). The mean storage times of group 1 (n = 24) and group 2 (n = 21) were 3.1 (1.7 SD) days and 7.7 (1.2 SD) days, respectively. At 1 and 5 minutes, the sensitivity of group 1 was consistently higher than that of group 2 (1 minute, 61% versus 38%; 5 minutes, 92% versus 62%), and no false-positive result was observed in either group. CONCLUSION: RUT remains highly sensitive and specific when it was stored at 4 degrees C for up to 5 days but should be discarded after that period.

Bacteriological Techniques↗

PubMed1996

Mass spectrometry and viral analysis.

BACKGROUND: Electrospray ionization (ESI) mass spectrometry is a powerful new approach for analyzing biomolecules and biomolecular complexes. Previous studies have provided evidence that non-covalent biomolecular complexes can be observed by ESI mass spectrometry; it is not clear, however, whether the native conformation of the biomolecules is maintained throughout the ionization and analysis process. We set out to address this question using live viruses. RESULTS: Viral ions have been generated in the gas phase using electrospray ionization mass spectrometry. These ions have been collected, following ion filtering through the mass analyzer, and then analyzed by transmission electron microscopy. Transmission electron microscopy revealed that rice yellow mottle virus and tobacco mosaic virus retained their respective spherical and rod-like ultrastructure. The viability of the isolated tobacco mosaic virus was confirmed by inoculation and infection of tobacco plants. CONCLUSIONS: These results demonstrate the utility of electrospray for supramolecular complexes with molecular weights of over 40 million Da and offer conclusive evidence that native biomolecular structures can be conserved through the electrospray process.

Mass Spectrometry↗

PubMed1995

Bone marrow and splenic granulocyte-macrophage colony-stimulating factor and transforming growth factor-beta mRNA levels in irradiated mice.

The effects of a myeloablative sublethal 775 cGy 60C gamma radiation exposure on endogenous bone marrow (BM) and splenic granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta (TGF-beta) mRNA levels were assayed in B6D2F1 female mice. BM and spleen were harvested from normal mice and irradiated mice on days 2, 4, 7, 10, and 14 after exposure. Cytokine mRNA levels were determined using reverse transcription-polymerase chain reaction. After irradiation, GM-CSF mRNA levels were significantly increased in the BM from days 2 to 10 and in the spleen from days 4 to 10. However, when BM and splenic GM-CSF protein levels were measured using Western dot blot, no increased protein levels were detected. Serum GM-CSF levels were likewise unchanged. Radiation exposure did not affect BM or splenic TGF-beta mRNA levels and this cytokine is known to be produced by cell populations similar to those that produce GM-CSF. These data suggest that radiation injury to hemopoietic tissues results in differential effects on GM-CSF and TGF-beta mRNA levels and that, in the case of GM-CSF, increased mRNA levels are not matched by increased protein production.

Agranulocytosis↗

PubMed1995

c-kit ligand gene expression in normal and sublethally irradiated mice.

The c-kit ligand (KL; Steel factor, mast cell growth factor, stem cell factor) is a hematopoietic factor that has been shown to act as a potent cofactor for hematopoietic growth and differentiation in vitro. The in vivo effects of KL, however, have been variable. To study the hematopoietic role of KL in vivo, we evaluated KL gene expression in both normal mice and mice recovering from myelosuppressive radiation exposure using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. In a single RNA sample, we found that the RT-PCR technique has high precision (co-efficient of variation, 15.7%). Amplifications of serial 1:2 dilutions of template RNA precisely correlated with starting RNA concentrations at 20 cycles or at 25 cycles, depending on the level of expression. Amplification of individual normal bone marrow and spleen cell RNA showed basal expression in all normal bone marrows but irregular expression in normal spleens. On day 2 after a sublethal 7.75-Gy (0.4 Gy/min) 60Co irradiation, splenic KL gene expression increased approximately 2.5-fold (P = .011), and bone marrow expression increased 15-fold (P = .004). During a 28-day postirradiation recovery period, KL expression increased in bone marrow on days 2 through 7. Splenic expression during the same period was more variable. In conclusion, the KL gene is invariably expressed in normal murine spleens. Postirradiation, recovering bone marrow and spleen both express increased levels of KL mRNA at day 2 and continue to express increased levels for several days postexposure. These data support a role for KL in the endogenous recovery of hematopoiesis after hypoplastic injury.

Animals↗

PubMed1995

Disease specificity of kinase domains: the src-encoded catalytic domain converts erbB into a sarcoma oncogene.

src and erbB are two tyrosine kinase-encoding oncogenes carried by retroviruses, which have distinct disease specificities. The former induces predominantly sarcomas, and the latter, leukemias. Src and ErbB have similar catalytic domains but have very different regulatory domains. A wealth of information exists concerning how different regulatory domains [Src homology 2 (SH2) and SH3 domains and autophosphorylation sites] control substrate and disease specificities. Whether the catalytic domain helps determine these specificities remains to be explored. Here we show that the Src catalytic domain is enzymatically active when substituted into the ErbB backbone and interacts with the ErbB regulatory domain. This ErbB/Src chimera displays autophosphorylation and substrate phosphorylation patterns different from those of both Src and ErbB. Neither SH2 and SH3 nor autophosphorylation sites are required for the Src catalytic domain to exert its fibroblast transforming ability. Most significantly, the catalytic domain can convert erbB from a leukemogenic oncogene into a sarcomagenic oncogene, suggesting that the leukemogenic determinants in part reside within the ErbB catalytic domain.

Animals↗

PubMed1995

A minor tyrosine phosphorylation site located within the CAIN domain plays a critical role in regulating tissue-specific transformation by erbB kinase.

Avian c-erbB encodes a protein that is homologous to the human epidermal growth factor receptor. Truncation of the amino-terminal, ligand-binding domain of this receptor results in an oncogene product which is a potent inducing agent for erythroleukemias but not fibrosarcomas in chickens. Here we show that mutation of a single tyrosine residue, p5, in the carboxyl terminus of the erbB oncogene product allows it to become sarcomagenic in vivo and to transform fibroblasts in vitro. Mutations of other autophosphorylation sites do not generate comparable effects. The increased transforming activity of the p5 mutant is accompanied by an elevated level of mitogen-activated protein kinase phosphorylation. By analogy to the human epidermal growth factor receptor, p5 is a minor autophosphorylation site and is located in a domain known to be involved in regulating calcium influx and receptor internalization (CAIN domain). This area of the erbB product has been found to be repeatedly deleted in various sarcomagenic avian erythroblastosis virus isolates. We precisely deleted the CAIN domain and also made point mutations of the acidic residues within the CAIN domain. In both cases, fibroblast-transforming potential is activated. We interpret these data to mean that p5 and its surrounding region negatively regulate fibroblast-transforming and sarcomagenic potential. To our knowledge, this represents the first point mutation of an autophosphorylation site that activates erbB oncogenicity.

Amino Acid Sequence↗

PubMed1995

DNA analysis of Huntington's disease in southern Chinese.

Allelic frequencies of RFLPs at loci closely linked to the HD gene, D4S95, D4S91, D4S141, and D4S90, were determined in 13 Huntington's disease (HD) patients from nine Chinese families and 129 normal subjects. These were similar for non-HD and HD chromosomes and the HD gene in Chinese is associated with multiple haplotypes. Hence the HD gene probably arose independently in the background haplotypes of the Chinese population. The heterozygosity rates for the two most useful RFLP sites are 0.659 for D4S95-AccI VNTR and 0.494 for D4S141-HindIII. (CAG)n repeat numbers ranged from 12 to 27 in 174 normal chromosomes. In 52 meiotic recombinations, the (CAG)n repeats were stably inherited in normal families. In HD families, 12 of 13 HD patients had expanded (CAG)n repeats of 40 to 58. Additionally, 10 asymptomatic family members had expanded (CAG)n repeats and the inheritance of the expanded repeat was unstable in these families.

Alleles↗

PubMed1995

Comparison of interleukin-1 alpha gene expression and protein levels in the murine spleen after lethal and sublethal total-body irradiation.

To understand the effects of ionizing radiation on the production of IL-1 alpha in vivo within a hematopoietic organ, we evaluated acute changes in splenic IL-1 alpha mRNA and IL-1 alpha protein after exposing B6D2F1 mice to lethal and sublethal 60Co radiation. Results suggest that in vivo, ionizing radiation induces a time- and dose-dependent accumulation of IL-1 alpha mRNA in the mouse spleen after exposure to gamma radiation. Time-dependent increases in the level of IL-1 alpha protein were also observed, although the magnitude of increased protein expression did not complement the magnitude of the accumulation of the message. Selective concentration of cells producing IL-1 alpha does not appear to account completely for the increase in splenic IL-1 alpha mRNA observed in this in vivo system.

Animals↗

PubMed1994

Modulation of erbB kinase activity and oncogenic potential by single point mutations in the glycine loop of the catalytic domain.

Avian c-erbB is activated to a leukemia oncogene following truncation of its amino-terminal ligand-binding domain by retroviral insertion. The insertionally activated transcripts encode protein products which have constitutive tyrosine kinase activity and can induce erythroleukemia but not sarcomas. We have previously found that a valine-to-isoleucine point mutation at position 157 (V157I mutant) within the tyrosine kinase domain of this truncated erbB can dramatically activate the sarcomagenic potential of the oncogene and increase the kinase activity of this oncoprotein. This mutation lies at position 157 of the insertionally activated c-erbB product, affecting a highly conserved valine residue of the glycine loop involved in ATP binding and phosphate transfer. To investigate the functional importance of this residue in the catalytic activity of kinases, we have introduced at this position, by site-directed mutagenesis, codons representing the remaining 18 amino acid residues. Most of the mutants have diminished activity, with six of them completely devoid of kinase activity, indicating the sensitivity of this region to conformational changes. Some of these mutants displayed increased kinase activity and greater transforming potential in comparison with IA c-erbB, but none had levels as high as those of the V157I mutant. In general, the sarcomagenic potential of the various erbB mutants correlated with their autophosphorylation state and their ability to cause phosphorylation of MAP kinase. However, there are important exceptions such as the V157G mutant, which lacks enhanced autophosphorylation but is highly sarcomagenic. Studies of this and other autophosphorylation site mutants point to the existence of an autophosphorylation-independent pathway in sarcomagenesis. The requirement for leukemogenic potential is much less stringent and correlates with positivity of kinase activity. When the valine-to-isoleucine substitution was put in context of the full-length erbB protein, the mutation relaxed the ligand dependence and had a positive effect on the transforming potential of the full-length c-erbB.

Animals↗

PubMed1994

Huntington's disease in Hong Kong Chinese: epidemiology and clinical picture.

In a territory-wide survey of Huntington's disease (HD) in the Chinese population of Hong Kong, 20 patients from 11 families were identified from 1984 to 1991, giving a low period prevalence of 3.7 per 10(6) population. Six patients had died by 1991, hence the point prevalence was even lower, being 2.5 per 10(6) population. The male to female ratio was 3:1. No paternal transmission effect on the age of onset was observed. Apart from these differences, the clinical and pathological features were similar to those seen in the West.

Adult↗

PubMed1994

Primary cerebral abscess due to Nocardia asteroides presenting as stroke.

Nocardial cerebral abscess, an uncommon condition, is usually secondary to a septic focus elsewhere in the body. We report a 44-year-old Chinese male patient who had primary nocardial cerebral abscesses due to Nocardia asteroides which presented with stroke-like episodes. He improved spontaneously between these episodes. The diagnosis was reached only after a contrast CT brain study and microbiological examination of specimens obtained during craniotomy. An early contrast CT study is important in avoiding any delay in diagnosis and treatment of this serious condition.

Abscess↗

PubMed1994

Cardiorespiratory response to lower body negative pressure.

The cardiovascular effects of supine lower body negative pressure (LBNP, 0 mm Hg, -8 mm Hg, -15 mm Hg, -25 mm Hg, -35 mm Hg, and -45 mm Hg) were studied in humans (n = 10). The LBNP's were applied in a random order (three per session) for 20 min, with 15 min between each LBNP. Leg blood flow, cardiac output (Q), stroke volume (SV) and estimated lung blood volume were significantly reduced at -15 mm Hg. Increasing LBNP to -35 mm Hg did not result in further changes. When the LBNP was increased to -45 mm Hg, Q and SV were lower than comparable values at -15 mm Hg. Heart rate was unchanged up to -25 mm Hg, after which it increased proportionally to the LBNP. Systolic blood pressure was maintained throughout. Diastolic blood pressure was unchanged below -45 mm Hg, but was significantly elevated at -45 mm Hg. Mean arterial pressure was maintained up to LBNP's of -35 mm Hg by increased vascular resistance, in spite of reduced thoracic blood volume, as indicated by reduced central venous pressure and Q. Greater levels of LBNP were outside the physiological adjustment range and blood pressure dropped progressively.

Adult↗

PubMed1993

Investigation of nimodipine pharmacokinetics in Chinese patients with acute subarachnoid haemorrhage.

Nimodipine pharmacokinetics was investigated in 12 Chinese patients with acute subarachnoid haemorrhage receiving an IV infusion of 1.6 or 2 mg/h (based on estimated body weight) for 10 days. Peripheral venous blood samples were collected for up to 4 days and plasma nimodipine was assayed by GC/ECD. The mean value was taken as the steady state concentration (Css) and Clearance (CL) (hourly dose/Css) was calculated. Eight survivors were given oral nimodipine (60 or 90 mg) every 6h (based on body weight), blood was sampled over 6 h and the plasma nimodipine level determined. The values for Css, CL and CL.kg-1 were 33.5 micrograms.l-1, 58 l.h-1 and 1.0 l.h-1 x kg-1 respectively; in survivors receiving the drug orally, bioavailability of the 30 mg tablet was 9%. In one very sick patient given crushed tablets by naso-gastric tube, the AUC was very low; in vitro studies indicated that adsorption of nimodipine by the tubing was unlikely to have been the cause. The pharmacokinetic findings in Chinese patients are comparable to previously reported values in Caucasians.

Acute Disease↗

PubMed1993

Differential responses in cyclic GMP formation induced by excitatory amino acids (EAA) and sodium nitroprusside (SNP) in various regions of the brain and of rats of varied age.

1. Sodium nitroprusside (SNP, 100 microM) caused a rapid and great increase of formation of cGMP in rat cerebellar slices. This effect was not blocked by L-NMMA (a NO synthetase inhibitor) or antagonists of the NMDA receptor complex (e.g. AP5 or MK 801). 2. Similarly, NMDA (100 microM) and glutamate (1 mM) caused a rapid but less significant increase of cGMP formation. This increase was blocked by NMDA receptor complex blockers (e.g. AP5, MK801 and kynurenate), and L-NMMA and L-nitroarginine. 3. In rats aged 12 days, both NMDA and kainate (at 100 microM) caused significantly increased levels of cGMP in the cerebellum, pons and medulla areas, whereas no significant alterations were found in the cerebral cortex, hippocampus or midbrain areas. 4. NMDA (100 microM) and SNP (300 microM) induced greater increases of cGMP in cerebellar slices in young (aged 13 days) animals than older ones of either sex. This effect decreased greatly after 35 days of age. In adult (2 months) animals the effect of NMDA had virtually disappeared whereas SNP was barely significantly present. 5. Our results suggest that brain region and age, but not sex, affected formation of cGMP induced by excitatory amino acids (EAA) and SNP. Furthermore, endogenous NO production is required by EAA, but not by SNP, in the formation of cGMP.

Aging↗

PubMed1993

N-hexane neuropathy in offset printers.

In an offset printing factory with 56 workers, 20 (36%) developed symptomatic peripheral neuropathy due to exposure to n-hexane. Another 26 workers (46%) were found to have subclinical neuropathy. The initial change in the nerve conduction study was reduced amplitude of the sensory action potentials, followed by reduced amplitude of the motor action potentials, reduction in motor conduction velocities and increase in distal latencies. These changes indicate primary axonal degeneration with secondary demyelination. Sural nerve biopsy in a severe case showed giant axonal swellings due to accumulation of 10nm neurofilaments, myelin sheath attenuation and widening of nodal gaps. The development of neuropathy bore no direct relationship to the duration of exposure, hence factors such as individual susceptibility may be important. Optic neuropathy and CNS involvement were uncommon and autonomic neuropathy was not encountered.

Adolescent↗

PubMed1993

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

BACKGROUND AND PURPOSE: This clinical trial investigates the effectiveness of intravenous glycerol therapy in patients with acute cortical infarction in whom intracerebral hemorrhage was rigorously excluded. METHODS: Within 48 hours of symptoms from their first ischemic stroke, 113 hospital inpatients were randomized into the trial, provided that hemorrhage was excluded by computed tomography and informed consent was obtained. Patients were stratified into alert, semicoma, and coma groups using the Glasgow Coma Scale. Treatment was allocated according to a double-blind, randomized protocol; 56 patients received 500 mL of 10% glycerol in saline over 4 hours on 6 consecutive days, and 57 patients received corresponding placebo treatment with saline. Using a variety of objective scoring systems, patient follow-up was up to 6 months. RESULTS: Corresponding measures of outcome in the glycerol and placebo groups were similar. At 6 months, respective mortality rates were 17 of 56 and 16 of 57, and mean +/- SD improvements in scores were 9.98 +/- 14.40 vs 10.51 +/- 12.68 (long-term), 1.12 +/- 7.20 vs 1.57 +/- 6.30 (prognostic), -1.94 +/- 5.53 vs -2.06 +/- 5.34 (Glasgow Coma Scale), and 21.72 +/- 23.40 vs 11.94 +/- 18.10 (Barthel Index rating in survivors). Hemolysis (generally subclinical) was the only adverse effect. CONCLUSIONS: There was no clinically or statistically significant difference in outcome between the groups; a trend toward greater functional recovery among survivors was evident after treatment with glycerol.

Acute Disease↗

PubMed1993

Basilar artery occlusion following yoga exercise: a case report.

Basilar artery occlusion developed in a 34 year old woman 2 months after adopting unusual neck postures during yoga practice. On angiography, her basilar artery was filled with intraluminal clot while the vertebral arteries were normal. We postulate that a severe reduction in blood flow and possibly an intimal tear triggered thrombosis of the vertebral artery and that the final stroke mechanism was artery-to-artery embolism.

Adult↗