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Biomedical subjects

M C Chung

Publications and source records attributed to M C Chung.

At least 91 records · Page 5Linked to original sources

Disposition of clozapine and desmethylclozapine in schizophrenic patients.

The disposition of the atypical clozapine and its desmethyl metabolite were evaluated in fourteen male chronic patients. A single 100 mg dose of clozapine was administered and blood sampling performed over the following 72 hours. The mean (SD) oral clearance and half-life of clozapine were 55.4 (29.7) L/hr and 13.7 (9.9) hours, respectively. The mean (SD) AUC for clozapine and desmethylclozapine was 2389.9 (1406) and 751.1 (622.9) ng.hr/mL, respectively. The elimination of the metabolite is rate limited by its formation from cloza-pine. A wide interpatient variability in clozapine and desmethylclozapine pharmacokinetics was observed.

Adult↗

Purification and properties of the L-amino acid oxidase from Malayan pit viper (Calloselasma rhodostoma) venom.

The L-amino acid oxidase of Malayan pit viper (Calloselasma rhodostoma) venom was purified to electrophoretic homogeneity. The molecular weight of the enzyme was 132,000 as determined by Sephadex G-200 gel filtration chromatography and 66,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is a glycoprotein, has an isoelectric point of 4.4, and contains 2 mol of flavin mononucleotide per mole of enzyme. The N-terminal amino acid sequence of the enzyme was A-D-D-R-N-P-L-A-E-E-F-Q-E-N-N-Y-E-E-F-L. Kinetic studies suggest the presence of a alkyl side-chain binding site in the enzyme and that the binding site comprises at least four hydrophobic subsites. The characteristics of the binding site differ slightly from those of cobra venom L-amino acid oxidases.

Amino Acid Oxidoreductases↗

Rapid purification of recombinant human tumor necrosis factor beta.

A rapid and improved method for the purification of recombinant human tumor necrosis factor beta (rhTNF-beta) from Escherichia coli HB 101 cells has been developed. The method utilized sequential steps of polyethylenimine (PEI) and ammonium sulfate precipitation to remove most of the extraneous proteins and nucleic acids from the cell extracts. The final step of purification consisted of DEAE-Sepharose chromatography at pH 7.5 in which rhTNF-beta was eluted with starting buffer. This procedure, when compared to the earlier methods of purification, is highly efficient since we could increase the overall yield of rhTNF-beta and reduce the purification time considerably. The final yield that we obtained from 1 liter of fermentation broth (containing approximately 80 g of wet cells) was 40-50 mg.

Amino Acid Sequence↗

The path to care in autism: is it better now?

Parents of children with autism often report problems associated with obtaining a diagnosis of their child's condition, family support, information, and appropriate services. To evaluate any changes in the situation over the last two decades, the families of all members of the West Midlands Autistic Society, age 19 years and below, were asked to fill in a questionnaire that covered aspects of detection, diagnosis, help and information received, and educational provision. Responses were obtained from 127 families, the children of whom formed an older group ages 10 years and above (n = 67) and a younger group ages 9 years and below (n = 61). Findings show that there have been improvements for the younger group in some areas, such as earlier referral, diagnosis, and statementing. However, the situation with respect to advice given by professionals and the support and provision available after referral is still much the same as that experienced by families of the older group of children. Many difficulties and hurdles remain which hinder parents and children on the path to care in autism.

Adolescent↗

A genomic region encoding stonefish (Synanceja horrida) stonustoxin beta-subunit contains an intron.

The polymerase chain reaction (PCR) has been used to amplify a 1899 base pair fragment from stonefish genomic DNA. A comparison of the translated nucleotide sequence of this product with the separately determined N-terminal amino acid sequence of the beta-subunit reveals the presence of a 416 bp intron at Gly 18. The nucleotide sequence following this intron encodes 476 amino acids whose sequence showed no homology to other known toxins. This region, however, contained amino acid sequences identical to internal peptide sequences determined separately from the toxin's beta-subunit.

Amino Acid Sequence↗

The amino acid sequences of two postsynaptic neurotoxins isolated from Malayan cobra (Naja naja sputatrix) venom.

The complete amino acid sequences of two postsynaptic neurotoxins (toxin-3 and toxin-5) isolated from Malayan cobra (Naja naja sputatrix) venom were determined by direct automated Edman degradation of peptides obtained from digests with various proteases. Toxin-3 and toxin-5 are both short-chain neurotoxins and their amino acid sequences are highly homologous to Naja naja atra and Naja naja philippinensis neurotoxin, respectively. Toxin-3 is unique in possessing aspartic acid (D) as the fifth residue, while all other homologous short-chain neurotoxins have asparagine (N) at the corresponding position.

Amino Acid Sequence↗

The influence of positivistic thought on nineteenth century asylum nursing.

The development of positivism, which had a considerable influence on the evolution of psychiatric thought and practice during the second half of the nineteenth century, is outlined. It was within this intellectual framework that figures such as Kraepelin, Bleuler and Schneider developed psychiatric nosologies and diagnostic criteria for certain mental illnesses. While there was little scientific evidence to support the claim that medical treatments had any beneficial effects on pyschiatric disorders, nevertheless psychiatric institutions were established in the mid-nineteenth century based on the medical model. Nurses were expected to observe, collect and report data on mental patients which were then presented to doctors for analysis. The intellectual climate of the asylums was such that nurses were not encouraged to question the scientific principles upon which the therapeutic regime was based, nor were they encouraged to seek a rationale for their daily observations and data collection. The specialized training for asylum nurses which was introduced towards the end of the nineteenth century did not give nurses their own professional identity, but rather reinforced the supremacy of medical knowledge in the care of the mentally ill. Trained nurses enhanced medical credibility, but did not progress care of the mentally ill because their training did not imply or encourage questioning of the positivistic basis of psychiatric treatment.

History, 19th Century↗

The Marchioness disaster: preliminary report on psychological effects.

The psychological after-effects on 27 survivors of the Marchioness riverboat disaster of 20 August 1989 are described. On measures of intrusive memories and psychological difficulties these subjects are significantly higher than population norms, and somewhat higher than psychiatric in-patient populations. Personality measures taken after the disaster show that neuroticism scores are very much higher than population norms, but personality measures were not correlated with distress.

Adult↗

Continuous epitopes of human lymphotoxin and their topographies.

Human lymphotoxin (hLT or TNF-beta) is a lymphokine that is structurally and functionally related to tumor necrosis factor alpha (TNF-alpha). The continuous epitopes of hLT were located by examining the cross-reaction between rabbit anti-hLT antibody and peptides derived from proteolytic digestion and chemical synthesis. Three antigenic sites, corresponding to residues 40-48, 83-94 and 139-147, of the protein sequence, were located by this approach. Since residues 49-57 also exhibited trace antigenicity, but residues 45-52 displayed no reaction, the whole peptide fragment consisting of residues 40-57 might be necessary for antigenicity. A comparison of the antigenic determinants with the loop structures obtained from X-ray crystallographic studies of hLT showed that all of the epitopes are found on or adjacent to functionally important domains.

Amino Acid Sequence↗

Isolation and characterization of pectin methylesterase from papaya.

Pectin methylesterase (PME) (EC 3.1.1.11) has been purified to apparent homogeneity from ripe papaya fruits. The purification protocol consisted of ammonium sulphate precipitation (60-80%) and cation exchange chromatography in CM Sepharose CL-6B and Mono S. Papaya PME consists of two components (PME 1 and PME 2), which have been shown to be isoenzymes by Ferguson plot analysis. The molecular weight of the enzyme is 27,000 while its isoelectric point is greater than pH 9.0. The N-terminal sequences of PME 1 and PME 2 are SVVTPNAVVADDGVFXFKTG. Both PME 1 and PME 2 showed optimum activities at pH 8.0 and 35 degrees C. The average Kms of PME 1 and PME 2 are 0.0071 and 0.0166 g/liter pectin respectively, while the corresponding average Vmaxs are 741 and 800 mumol methanol/min/mg protein, respectively. Papaya pectin methylesterase is activated by cations, but the effect is more pronounced for divalent than monovalent cations. Inhibition studies showed that sucrose is a noncompetitive inhibitor while p-chloromercuribenzoic acid has no significant effect on its activity.

Amino Acid Sequence↗

Pyridylethylation of cysteine residues in proteins.

A procedure is described for using an inert polyvinylidene difluoride type membrane (e.g., ProBlott) as a matrix for on-membrane gas-phase pyridylethylation and as a desalting (cleanup) support following the solution phase pyridylethylation of cysteine residues in proteins. As a desalting support for 200 pmol of cardiotoxin, the membrane-derived sample gave a better recovery of phenylthiohydantoin (PTH)-amino acids during N-terminal sequencing compared to the sample obtained by rpHPLC. Using on-membrane gas-phase pyridylethylation, followed by replacement of glass-fiber filter disc and membrane washing/drying in vacuo, it was possible to eliminate the broad background peak that coeluted with PTH-Ala in the HPLC chromatogram completely. Using this modified procedure, there was no evidence of N-terminal alkylation of the amino-termini of proteins.

Alkylation↗

Selective antiproliferative effects of thymidine.

A substance with antiproliferative bioactivity in an aqueous extract of Cordyline terminalis was purified and identified by mass spectrometry to be the natural nucleoside, thymidine. 10(-5) M Thymidine inhibited EL4 cell replication and decreased cell viability after 12-24 h. The effect was highly specific for this nucleoside. Treated cell cultures showed a significant increase in S phase cells and a corresponding decrease in G1 phase cells. Nitrobenzylthioinosine (which prevented facilitated entry of thymidine) protected cells from the antiproliferative action of thymidine. A human breast cancer cell line (MCF7) was also growth-inhibited by 10(-5) M thymidine but a murine lymphoma cell line (K36) was not. Thus, submillimolar thymidine has effects on cell proliferation which are selective both with respect to specificity for the compound and for different tumour cell lines.

Animals↗

Determination of clozapine and desmethylclozapine in human plasma by high-performance liquid chromatography with ultraviolet detection.

A method using reversed-phase high-performance liquid chromatography for the simultaneous determination of clozapine and its desmethyl metabolite in human plasma has been established. Clozapine and N-desmethylclozapine were extracted with n-hexane-isoamyl alcohol (98.5:1.5, v/v). Protriptyline served as the internal standard. The limits of detection for clozapine and desmethylclozapine are 2 and 1 ng/ml, respectively. The sensitivity and precision of this method can be utilized for pharmacokinetic studies and therapeutic drug monitoring regimens.

Adult↗

On describing the psychological struggle of child sexual abuse victims through Kierkegaard's concept of self.

The aim of this paper is to use Soren Kierkegaard's concept of self to demonstrate some psychological phenomena of child sexual abuse victims. Their self is to a large extent determined by extreme outer circumstances i.e. the abuse and the abusers. In order to cope with the consequent psychological pain, such children employ powerful defense mechanisms which consequently, however, means that they remain longer in the abuse. Psychotherapies are attempts to help them to create their own self and gradually come out of their abuse. However, such creation of oneself is only carried out within their concretely traumatized self.

Adaptation, Psychological↗

Isolation and characterization of a hemorrhagin from the venom of Calloselasma rhodostoma (Malayan pit viper).

The major hemorrhagin (termed rhodostoxin) of the venom of Calloselasma rhodostoma (Malayan pit viper) was purified to electrophoretic homogeneity by Sephadex G-200 gel filtration followed by high performance ion exchange chromatography. The purified hemorrhagin also yielded a single peak in reversed-phase HPLC. It had an isoelectric point of 5.3 and a mol. wt of 34,000. Rhodostoxin exhibited potent proteolytic, hemorrhagic and edema-inducing activities but was not lethal to mice at a dose of 6 microgram/g (i.v.). Treatment of rhodostoxin with EDTA eliminated both the proteolytic and hemorrhagic activities completely. The N-terminal sequence of rhodostoxin was determined to be NHEIKRHVDIVVVXDSRFCTK.

Amino Acid Sequence↗

Purification and partial characterization of two cytolysins from a tropical sea anemone, Heteractis magnifica.

Two cytolysins, designated as magnificalysins I and II, were purified from a tropical sea anemone, Heteractis magnifica (formerly Radianthus ritteri). The purification steps involved Sephadex G-50 and CM-Sepharose chromatography followed by Mono S and Phenyl-Superose Fast Protein Liquid Chromatography. The relative mol. wt of magnificalysins I and II, determined by SDS-PAGE, was approximately 19,000, while their isoelectric points, determined by isoelectric focusing in immobilized pH gradients, were 9.4 and 10.0, respectively. Those toxins were found to have haemolytic and lethal activities. The haemolytic activities of magnificalysins I and II were 3.6 x 10(4) HU/mg and 3.3 x 10(4) HU/mg, while their LD50 (i.v., mice) values were approximately 0.14 microgram/g and 0.32 microgram/g, respectively. The amino acid composition and N-terminal sequences of magnificalysins I and II were also obtained. They do not possess any cysteine or cystine residue, but are rich in basic and hydrophobic amino acids. The N-terminal amino acid sequences of magnificalysins I and II are ALAGTIIAGASLTFKILDEV and SAALAGTIIDGASLGFDILNKV, respectively. These are highly homologous to cytolysins from other sea anemones, particularly cytolysin III from Stichodactyla helianthus, a Caribbean anemone.

Amino Acid Sequence↗

Molecular cloning of a cardiotoxin structural gene from Malayan spitting cobra (Naja naja sputatrix).

The structural gene and cDNA encoding cardiotoxin in Naja naja sputatrix have been cloned and characterized with a view to study the gene protein relationships and also to produce pure protein in large amounts. Using the polymerase chain reaction on the total RNA isolated from the venom glands, the structural gene (180 bp) has been synthesized and expressed in Escherichia coli to produce a fusion protein with beta-galactosidase. Immunoblotting using polyclonal antibodies raised against the total venom in rabbits demonstrated the presence of cross-reacting proteins in plaques produced by recombinant lambda gt11 phages.

Amino Acid Sequence↗