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Biomedical subjects

M C Chung

Publications and source records attributed to M C Chung.

At least 55 records · Page 3Linked to original sources
PubMed1997

Proteolytic specificity of rhodostoxin, the major hemorrhagin of Calloselasma rhodostoma (Malayan pit viper) venom.

The proteolytic specificity of rhodostoxin, the major hemorrhagin from Calloselasma rhodostoma (Malayan pit viper) venom was investigated using oxidized B-chain of bovine insulin as substrate. Six peptide bonds were cleaved: Ser9-Hist10, His10-Leu11, Ala14-Leu15, Tyr16-Leu17, Gly20-Glu21 and Phe24-Phe25. Deglycosylated rhodostoxin, however, cleaved primarily at Arg22-Gly23.

Amino Acid Sequence↗
PubMed1997

Synthesis and in vitro evaluation of potential antichagasic dipeptide prodrugs of primaquine.

American trypanosomiasis (Chagas' disease) is an endemic parasitic disease afflicting more than 20 million people in Latin America. Currently, therapy is unsatisfactory and only two drugs are available. Primaquine, an antimalarial drug, has trypanocidal activity. Dipeptide derivatives of primaquine, Phe-Arg-PQ, Lys-Arg-PQ, and Phe-Ala-PQ, were synthesized. The choice of the peptides was based on the primary specificity of cruzipain, the major cysteine proteinase from T cruzi. The prodrugs obtained were tested on the LLC-MK2 cell culture infected with trypomastigotes forms of T. cruzi. Phe-Arg-PQ, Lys-Arg-PQ, and Phe-Ala-PQ were active in all stages.

Animals↗
PubMed1997

Adrenergic and nitrergic responses of the rat isolated anococcygeus muscle to a new toxin (makatoxin I) from the venom of the scorpion Buthus martensi Karsch.

1. Makatoxin I (MkTx I) is a new toxin purified from the venom of the scorpion Buthus martensi Karsch. Contractile (excitatory, adrenergic) and relaxant (inhibitory, nitrergic) responses of the rat isolated anococcygeus muscle (Acm) to MkTx I were investigated. 2. MkTx I (0.28 microM) produced a rapid and very marked rise in the tone of the Acm which then gradually wanted to the control baseline. Phentolamine (5 microM), guanethidine (5 microM), tetrodotoxin (2 microM) and reserpine pretreatment in vivo (5 mg kg-1 s.c. at 24 hr and 5 mg kg-1 i.p. at 3 h) completely blocked the contractile responses of the Acm to MkTx I. The responses to noradrenaline (NA) were blocked by phentolamine, but were potentiated by guanethidine. 3. MkTx I (0.28 microM) also marked and rapidly relaxed the tone of the carbachol (CCh; 3 microM), precontracted Acm. The addition of sodium nitroprusside (SNP; 1 microM) also produced a marked and rapid relaxation of the Acm. TTx (2 microM) or NG-nitro-L-arginine methylester (L-NAME, 50 microM) markedly inhibited the relaxant responses of the Acm to field stimulation (FS) as well as to MkTx I, but not the responses to SNP. 4. Therefore, the contractile responses of the rat anococcygeus muscle to MkTx I can be attributed to the release of transmitter NA on postjunctional alpha-adrenoceptors, whereas the relaxant responses of the Acm to MkTx I involve the release of nitric oxide as the neurotransmitter which, presumably, results in the activation of the enzyme guanylate cyclase leading to relaxation of the muscle.

Amino Acid Sequence↗
PubMed1997

A critique of the concept of quality of life.

Taking a philosophical approach, ancient Greek philosophers and Christians began to investigate the concept of quality of life. Later, such philisophical pursuit was replaced by the school of positivism, which indicated that science was and still is the only valid form of enquiry. Through such positivistic science, the metaphysical nature of the concept of quality of life is thought to be uncovered. However, the later Wittgensteinian philosophical thoughts demonstrated that there is no metaphysical understanding of any concepts but there is only knowledge of playing language games. In the light of this philosophy, prior to any scientific investigations, researchers have already understood and agreed on the concept of quality of life by playing language games. From the above philosophical analyses, outlines some implications for health care research.

Health Services Research↗
PubMed1997

Recent service evaluation research on people with learning difficulties.

Substantial research on the evaluation of residential services for people with learning difficulties emerged over the last ten years in the UK. Reviews some of the major findings (N = 14). Their measures on the effectiveness of services were based on three components: the reduction of clients' challenging behaviour; the level of engagement between staff and clients; and clients' community involvement. An overall impression showed inconsistency and controversy in the first two components but a negative trend in the third. Discusses some methodological issues and suggests other components for service evaluation research.

Community-Institutional Relations↗
PubMed1997

Assessing the need for challenging behaviour services in an English health district.

The aim of the present study was to assess the health care needs for people with learning difficulties who display challenging behaviour in a newly established health district. Ninety-eight clients were studied, using Disability Assessment Schedule (DAS), Aberrant Behaviour Checklist (ABC) and The Psychopathology Inventory for Mentally Retarded Adults (PIMRA). The results showed that a large proportion of them were mobile, continent and able to feed themselves. Almost half had no problems in communication but less than half were sociable. On the whole, they did not have adequate skills. A large proportion of them did not present severe challenging behaviour and did not suffer from psychiatric illnesses, apart from inappropriate adjustment disorder. Correlation coefficients showed that there were relationships between challenging behaviours and some of clients' disabilities and inappropriate adjustment disorder.

Adolescent↗
PubMed1997

MR566A and MR566B, new melanin synthesis inhibitors produced by Trichoderma harzianum. I. Taxonomy, fermentation, isolation and biological activities.

New melanin synthesis inhibitors (MR566A and B) and six related known isocyanocyclopentenes were isolated from the fermentation broth of Trichoderma harzianum. The IC50 values of MR566A and B against mushroom tyrosinase were 1.72 and 47 microM, respectively. They inhibited melanin biosynthesis in B16 melanoma cells with MIC values of 0.1 and 2.2 microM, respectively. Also isolated from the same culture extract of T. harzianum was a new oxazole (MR93B), which showed no inhibitory activity against mushroom tyrosinase at a concentration of 1,000 microg/ml.

Animals↗
PubMed1997

MR566A and MR566B, new melanin synthesis inhibitors produced by Trichoderma harzianum. II. Physico-chemical properties and structural elucidation.

New melanin synthesis inhibitors (MR566A and B) and six related known isocyanocyclopentenes were isolated from the fermentation broth of Trichoderma harzianum, and their structures were elucidated by spectroscopic methods. The structures of novel isocyanides, MR566A (1) and B (2), were elucidated as 1-(3-chloro-1,2-dihydroxy-4-isocyano-4-cyclopenten-1-yl)etha nol, 1-(1,2,3-trihydroxy-3-isocyano-4-cyclopenten-1-yl)ethanol, respectively. The structure of novel oxazole, MR93B (9), was elucidated as 4-[(1Z)-3-hydroxy-2-hydroxymethyl-1-propen-1-yl]oxazole.

Cyclopentanes↗
PubMed1996

Improvements on the purification of mannan-binding lectin and demonstration of its Ca(2+)-independent association with a C1s-like serine protease.

Mannan-binding lectin (MBL), previously called 'mannan-binding protein' or MBP, is a plasma C-type lectin which, upon binding to carbohydrate structures on micro-organisms, activates the classical pathway of complement. Purification of MBL relies on its Ca(2+)-dependent affinity for carbohydrate, but existing methods are susceptible to contamination by anti-carbohydrate antibodies. In the present study a sequential-sugar-elution method has been developed which can achieve a preparation of virtually pure MBL and its associated serine protease (MBL-associated serine protease, MASP) by two steps of affinity chromatography. In further separation of MASP from MBL, it was found that activated MASP was associated with MBL independent of Ca2+. Since MBL was found to bind to underivatized Sepharose 4B, the MBL-MASP complex was purified using Sepharose 4B and protease inhibitors were included to purify the complex with MASP in its proenzyme form. Analysis of thus-purified MBL-MASP complex by gel filtration on a Sephacryl S-300 column at pH 7.8 showed that the proenzyme MASP was also associated with MBL independently of Ca2+, but that the complex could be disrupted at a low pH (5.0). Therefore the mechanism of MBL-MASP-mediated complement activation appears to be significantly different from the C1-mediated classical pathway.

Calcium↗
PubMed1996

Stonustoxin is a novel lethal factor from stonefish (Synanceja horrida) venom. cDNA cloning and characterization.

Stonustoxin (SNTX) is a multifunctional lethal protein isolated from venom elaborated by the stonefish, Synanceja horrida. It comprises two subunits, termed alpha and beta, which have respective molecular masses of 71 and 79 kDa. SNTX elicits an array of biological responses both in vitro and in vivo, particularly a potent hypotension that appears to be mediated by the nitric oxide pathway. As a prelude to structure-function studies, we have isolated and sequenced cDNA clones encoding the alpha- and beta-subunits of SNTX from a venom gland cDNA library. The deduced amino acid sequence of neither subunit shows significant homology with any known protein. Protein sequence alignment does, however, show the subunits to be 50% homologous to each other and implies that they may have arisen from a common ancestor. The subunits of this novel toxin lack typical N-terminal signal sequences commonly found in proteins that are secreted via the endoplasmic reticulum-Golgi apparatus pathway, indicating the possibility of its being secreted by a non-classical pathway, which is not clearly understood. The SNTX subunits have been expressed in Escherichia coli as cleavable fusion proteins that cross-react with antibodies raised against the native toxin. To the best of our knowledge, this is the first complete sequence of a fish-derived protein toxin to be reported.

Amino Acid Sequence↗
PubMed1996

The complete sequence of a Singapore isolate of odontoglossum ringspot virus and comparison with other tobamoviruses.

The complete sequence of a Singapore isolate of odontoglossum ringspot virus (ORSV-S1) comprises 6609 nucleotides (nt) and four open reading frames (ORFs 1 to 4). The 126/183-kDa RNA-dependent RNA polymerase (RdRp), 33-kDa movement protein (MP) and 18-kDa coat protein (CP) cistrons are located at nt 63-3401/4901, 4807-5718, and 5721-6197 on the genome, respectively. The 5' UTR contains three copies of an 8-base direct repeat and (CAA)n motifs. Characteristic tRNA-like structure and three consecutive homologous regions were present in the 3' UTR. The genomic RNA and MP of ORSV-S1 are one of the longest among all members of the TOV group. Phylogenetic analysis of all four genes indicates evolutionary divergence, but within each gene there are some degrees of evolutionary convergence. The conserved amino acid sequences in the MP can be used for the classification of tobamoviruses.

Amino Acid Sequence↗
PubMed1996

The structure and expression of an hsc70 gene from Lycopersicon esculentum.

A tomato hsc70 genomic clone (Lehsc70-3; Lycopersicon esculentum heat-shock cognate 70-3) was obtained by screening a genomic library with the tomato Lehsc70-2 cDNA. Two restriction fragments of 2.6 and 5 kb, which compose the Lehsc70-3 gene, were subcloned into pBluescriptIIKS+ and analyzed. Transcript mapping reveals that the mature Lehsc70-3 mRNA contains a 122-nt 5' untranslated region (UTR), a coding region of 1956 nt corresponding to a polypeptide of 651 amino acids, an intron of 717 nt and a 3' UTR. Analysis of genomic DNA indicates that Lehsc70-3 is present as a low-copy-number gene. We note that the sequence upstream from the coding region of Lehsc70-3 shares common features with a number of hsc/hsp genes. High-temperature treatment (37 degrees C) caused a twofold increase in the level of the Lehsc70-3 mRNA. However, Lehsc70-3 has also been expressed at substantial levels in tomato vegetative tissues, suggesting a general function of this hsc70 gene in L. esculentum.

Amino Acid Sequence↗
PubMed1996

Structural studies of a major hemorrhagin (rhodostoxin) from the venom of Calloselasma rhodostoma (Malayan pit viper).

The complete amino acid sequence, disulfide linkages, glycosylation sites, and carbohydrate structure of rhodostoxin, the major hemorrhagin from Calloselasma rhodostoma (Malayan pit viper), have been determined. This sequence confirmed the deduced amino acid sequence of the putative hemorrhagic protein encoded by the prorhodostomin cDNA of C. Rhodostoma. Rhodostoxin contained four disulfide bonds that link Cys19-Cys60, Cys117-Cys198, Cys157-Cys182, and Cys159-Cys165. It is the first four-disulfide proteinase reported among all known venom metalloproteinases, which are either of the two-disulfide or three-disulfide type. Peptide-mapping and dot-blotting experiments showed the presence of two glycopeptides. Subsequent sequencing of these peptides established that the N-glycosylation sites are located at residues 91 and 181 of the amino acid sequence of the matured protein. Mass spectrometric analyses of these glycopeptides showed that they contain an oligosaccharide structure consisting of 4 units of N-acetylglucosamine, 5 units of hexose, 1 unit of fucose, and 2 units of neuraminic acids. The complete carbohydrate structure was then established by 2-D mapping analysis of the pyridylamino-oligosaccharides after hydrazinolysis and pyridylamination of the glycan chains.

Amino Acid Sequence↗
PubMed1996

Maladaptive behaviour in Prader-Willi syndrome in adult life.

Thirty adults with Prader-Willi syndrome (PWS) were compared with 30 adults with non-specific learning disability matched for age, sex and severity of mental retardation. Maladaptive behaviour was assessed with the Aberrant Behavior Checklist (ABC), a 58-item structured interview which rates behaviours from 0 (not a problem) to 3 (severe problem) and which yields five factors (I) irritability, agitation; (II) lethargy, withdrawal; (III) stereotypic behavior; (IV) hyperactivity, non-compliance; and (V) inappropriate speech). The PWS sample had significantly higher factor I (P < 0.001) and factor V (P < 0.05) scores. The PWS sample had mean scores above 1 for 17 ABC items; the contrast subjects had no mean scores above 1. The factor I scores for the PWS sample were similar to those of inpatients in hospital facilities for adults with mental retardation and mental illness or severely challenging behaviour. The results support previous work, and extend it by suggesting that temper tantrums, self-injury, impulsiveness, lability of mood, inactivity and repetitive speech are characteristic behaviours in PWS in adult life. Studies of the reasons for heterogeneity in behaviour are now needed.

Activities of Daily Living↗
PubMed1996

Responses and needs in a changing situation: staff who work with people with learning disability.

Questionnaires were sent to residential care staff working with people with learning disability both in hospital and community settings, to explore any changes resulting from implementation of the policy of care in the community. Information was obtained on the current job situation of staff, their opinions on the effect of the policy of care in the community, their training needs, and perceived job prospects for the future. Findings for staff working in a hospital setting are compared with those of staff working in the community and discussed in the context of changing demands and conditions.

Adult↗
PubMed1996

Linear epitopes of sperm whale myoglobin identified by polyclonal antibody screening of random peptide library.

Distinct enhancement of antibody-specific clones was apparent during the screening against random peptide libraries with antigen-specific polyclonal antibodies. Several sequence motifs obtained from these screenings were homologous with the primary sequence of myoglobin. Two of these motifs have been confirmed as antigenic determinants by competitive inhibition tests using eight-branched synthetic peptides. One of the peptides has a sequence that corresponds to amino acid residues 42-50, KFDRFKHLK, of the myoglobin sequence. This is a new epitope of myoglobin that is reported for the first time. The epitope is located precisely in the "turn' or "loop' region between helices C and D of the crystal structure of myoglobin. The second antibody binding site has a sequence of DIAAKYKELGYQG, and this is located between residues 141-153, which is the C-terminus of myoglobin. This epitope encompassed two linear epitopes of myoglobin, amino acid residues 145-151 and 147-153, that have been reported earlier based on immunochemical characterisation of cleavage fragments of the protein. These results clearly indicate that epitope mapping using polyclonal antibodies against random peptide libraries can identify new epitopes precisely, as well as confirm epitopes of myoglobin obtained earlier using established methodologies.

Animals↗
PubMed1996

Cloning of the aldehyde reductase gene from a red yeast, Sporobolomyces salmonicolor, and characterization of the gene and its product.

An NADPH-dependent aldehyde reductase (ALR) isolated from a red yeast, Sporobolomyces salmonicolor, catalyzes the reduction of a variety of carbonyl compounds. To investigate its primary structure, we cloned and sequenced the cDNA coding for ALR. The aldehyde reductase gene (ALR) comprises 969 bp and encodes a polypeptide of 35,232 Da. The deduced amino acid sequence showed a high degree of similarity to other members of the aldo-keto reductase superfamily. Analysis of the genomic DNA sequence indicated that the ALR gene was interrupted by six introns (two in the 5' noncoding region and four in the coding region). Southern hybridization analysis of the genomic DNA from S. salmonicolor indicated that there was one copy of the gene. The ALR gene was expressed in Escherichia coli under the control of the tac promoter. The enzyme expressed in E. coli was purified to homogeneity and showed the same catalytic properties as did the enzyme from S. salmonicolor.

Alcohol Oxidoreductases↗