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Biomedical subjects

R Chen

Publications and source records attributed to R Chen.

At least 469 records · Page 26Linked to original sources

[Total pelvic exenteration for local advanced rectal carcinoma: analysis of 20 patients].

20 patients of total pelvic extenteration (TPE) were performed from 1989 to 1995 for local advanced rectal carcinoma. The incidence of operative complications was 65% with a mortality of 5%. 19 patients were followed up for 3-42 months, 7 patients died with an average life-span of 14.1 months. It seemed to us that the results of conservative therapy was usually disappointing for local advanced rectal carcinoma and and TPE is the better management of choice for relieving patient's symptoms and improving their survival rates.

Adenocarcinoma↗

Fractal geometry study of DNA binding proteins.

The main aim of this paper is to search for three-dimensional structure homology between DNA-binding proteins. The run of a protein's main chain is depicted by a sequence, which is constituted by the fractal indices, where each index describes how twisted or extended a partial protein segment is. Two proteins are compared by constructing a dot matrix between two such sequences, and the matrix is searched for dot-concentrated rectangles which is an indication of tertiary homology. This new method is applied to DNA-binding proteins which are selected from Brookhaven Protein Data Bank, among which most contain a helix-turn-helix motif. The dot-matrix shows that there is tertiary homology between two motifs. Other interesting results are also presented in this paper.

Animals↗

Analysis of potential functional regions using local degeneracy: mutational hotspots in human factor IX are localized in high-degeneracy regions.

To study the relationship between the potential functional regions with the primary amino acid sequence, we introduced a new factor termed local degeneracy to analyze the degree of the degeneracy in a given segment of the protein. Using the defined local degeneracy, we have analyzed the human coagulation Factor IX (Christmas factor) which is an essential component of the clotting cascade. The mutational hotspots in Factor IX are primarily distributed in the high-degeneracy regions, suggesting a direct correlation of the functional regions with high degree of the degeneracy. This method may be useful to predict and to evaluate potential functional domains of a protein.

Animals↗

Binding of bromine-substituted analogs of methylphenidate to monoamine transporters.

We synthesized the o-, m- and p-bromo derivatives of dl-threo-methylphenidate from the corresponding bromophenylacetonitriles by modification of the literature synthesis of methylphenidate (Panizzon, Helv. Chim. Acta 1944, 27, 1748). In in vitro binding assays all three dl-threo bromo compounds had higher affinities than methylphenidate for dopamine transporter sites labeled with [3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]WIN 35,428; IC50 = 13, 4, 20 and 82 nM for o-, m-, and p-bromo compounds, and unsubstituted methylphenidate, respectively). They also bound more strongly than methylphenidate to norepinephrine reuptake sites labeled with [3H]nisoxetine (IC50 = 32, 20, 31 and 440 nM, respectively), but were weak ligands (IC50 > or = 1 microM) at the serotonin transporter labeled with [3H]paroxetine. In addition, the bromine substituted derivatives demonstrated similar activity to methylphenidate in vivo in rodents in terms of inhibition of heart uptake of [3H](-)-norepinephrine, elevation of striatal extracellular dopamine, and stimulation of locomotor activity.

Animals↗

Tradescantia stamen hair mutation bioassay.

The Tradescantia stamen hair mutation (Trad-SH) assay (clone 4430) was evaluated for its efficiency and reliability as a screen for mutagens in an IPCS collaborative study on plant systems. Four coded chemicals, i.e. azidoglycerol (AG, 3-azido-1,2-propanediol), N-methyl-N-nitrosourea (MNU), sodium azide (NaN3) and maleic hydrazide (MH) were distributed by the Radian Corporation to the five laboratories in five different countries for testing mutagenicity. Pink mutations were scored between the 7th and 14th day according to a standard protocol. Test results from the five individual laboratories were analyzed and compared after decoding. One out of the two laboratories that conducted tests on AG demonstrated that AG is a mutagen with genetically effective doses ranging from 50 to 100 micrograms/ml. MH yielded positive responses in all laboratories but no linear dose-response pattern was observed. The effective dose range for MH was between 1 and 45 micrograms/ml. The mutagenicity of MNU was reported by five laboratories in the dose range between 10 and 80 micrograms/ml. NaN3, which exhibited a relatively high degree of toxicity, elicited a positive mutagenic response in three of the five laboratories in which it was tested. As with MNU the effective dose for NaN3 ranged between 3 and 80 micrograms/ml. The results from the current study substantiate the Trad-SH assay as a reliable system for screening chemicals for their potential mutagenic effects. Although the study was carried out exclusively under laboratory conditions, a survey of the current literature would indicate that the Trad-SH assay could be an effective in situ monitor of gaseous, liquid, and radioactive pollutants as well.

Azides↗

Tradescantia micronucleus bioassay.

Four coded chemicals, azidoglycerol (AG), N-methyl-N-nitrosourea (MNU), sodium azide (NaN3), and maleic hydrazide (MH), were tested with the Tradescantia micronucleus (Trad-MCN) bioassay by five independent laboratories from five different countries. The purpose of this international collaborative study was to evaluate four plant bioassays, of which the Trad-MCN assay was one, for their sensitivity, efficiency and reliability. The study was carried out under the sponsorship of the International Programme on Chemical Safety. All laboratories adhered to a standard Trad-MCN protocol which suggested that three replicate tests be conducted with each chemical. The results reported by all laboratories, although not equal, showed good agreement among the laboratories. In fact, all five laboratories obtained positive results with MH and MNU, while four of the five laboratories achieved positive results with NaN3. AG was tested in only three laboratories. Two reported negative results, while one reported positive results but only at a single high dose. The data from this study suggest that under normal conditions, the Trad-MCN bioassay is an efficient and reliable short-term bioassay for clastogens. It is suitable for the rapid screening of chemicals, and also is specially qualified for in situ monitoring of ambient pollutants.

Azides↗

Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary.

Corticotropin-releasing factor (CRF) is a major hypophysiotropic peptide regulating pituitary-adrenal response to stress, and it is also widely expressed in the central nervous system. The recent cloning of cDNAs encoding the human and rat CRF receptors has enabled us to map the distribution of cells expressing CRF receptor mRNA in rat brain and pituitary by in situ hybridization. Receptor expression in the forebrain is dominated by widespread signal throughout all areas of the neo-, olfactory, and hippocampal cortices. Other prominent sites of CRF receptor mRNA expression include subcortical limbic structures in the septal region and amygdala. In the diencephalon, low levels of expression are seen in a few discrete ventral thalamic and medial hypothalamic nuclei. CRF receptor expression in hypothalamic neurosecretory structures, including the paraventricular nucleus and median eminence, is generally low. In the brainstem, certain relay nuclei associated with the somatic (including trigeminal), auditory, vestibular, and visceral sensory systems, constituted prominent sites of CRF receptor mRNA expression. In addition, high levels of this transcript are present in the cerebellar cortex and deep nuclei, along with many precerebellar nuclei. In the pituitary, moderate levels of CRF receptor mRNA expression were detected throughout the intermediate lobe and in a subset of cells in the anterior lobe identified as corticotropes by concurrent immunolabeling. Overall, the central distribution of CRF receptor mRNA expression is similar to, though more expansive than, that of regions reported to bind CRF, and it shows limited overlap with loci expressing CRF-binding protein. Interestingly, CRF receptor mRNA is low or undetectable in several cell groups implicated as central sites of CRF action.

Adrenocorticotropic Hormone↗

Cloning and functional expression of a Drosophila gamma-aminobutyric acid receptor.

A cDNA encoding a functional gamma-aminobutyric (GABA)-activated Cl- channel has been isolated from an adult Drosophila head cDNA library. When expressed in Xenopus laevis oocytes, the subunit functions efficiently, presumably as a homooligomeric complex and is activated by GABA or muscimol. GABA-evoked currents are highly sensitive to antagonism by picrotoxin but are insensitive to bicuculline, RU 5135, or zinc. Pentobarbitone greatly enhances GABA-evoked currents, whereas the neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one demonstrates a large reduction in both the potency and maximal effect when compared with its actions upon vertebrate GABA type A receptors. Although zinc-insensitive, the subunit is also insensitive to flunitrazepam. Hence, the GABA receptors formed by this subunit exhibit a unique pharmacology when compared with vertebrate GABA type A receptors or those composed of rho subunits. Because the receptor-channel complex functions as a homooligomer, this subunit may be of value in mutagenesis studies aiming to define drug-binding sites.

Amino Acid Sequence↗

Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes in the HLA class III region. Molecular cloning, exon-intron structure, composite retroposon, and breakpoint of gene duplication.

The correlation of many HLA-associated autoimmune and genetic diseases with the polymorphic complement C4 genes may be attributed to the presence of disease susceptibility genes in the close proximity of C4. We have cloned and characterized a pair of partially duplicated genes, RP1 and RP2, located 611 base pairs upstream of the human C4A and C4B genes, respectively. The putative RP protein, consisting of 364 amino acid residues, is basic and highly hydrophilic. There is a bipartite nuclear localization signal at residues 114-131 and therefore RP may be a nuclear protein. Northern blot analysis suggested that RP is ubiquitously expressed. The 5' region of the RP1 gene is CpG rich, which is a characteristic of housekeeping genes. The RP1 gene contains nine exons. Located in the fourth intron is a cluster of Alu elements, and a newly defined composite retroposon SVA with a SINE, multiple copies of GC-rich VNTRs and an Alu element altogether enclosed by direct terminal repeats. Members of SVA are also present in the complement C2 gene located about 20 kilobases upstream of RP1 in the HLA and in the cytochrome CYP1A1 gene. Determination of the DNA sequences for RP2 from two different HLA haplotypes revealed identical hybrid sequences which resulted from fusion of RP with the tenascin-like Gene X and truncation of the 5' regions of both genes. Cumulative data suggest that the four tandemly arranged genes RP, complement C4, steroid 21-hydroxylase (CYP21), and Gene X altogether form a modular structure, RCCX. The number of RCCX modules varies from one to three or more in the population. Absence of the truncated genes RP2 and Gene XA have been detected in genomes with single RCCX modules. Duplication of the RCCX modules probably occurred before the speciation of great apes and humans as they contain the same breakpoint region of RP and Gene X gene duplication.

Alleles↗

Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis.

The efficacy of ketoprofen in the treatment of acute clinical mastitis was evaluated in a clinical trial comprising a non-blind controlled study and a blind, placebo-controlled study. All the cows were treated with 20 g sulphadiazine and 4 g trimethoprim intramuscularly upon diagnosis, and half the dosage was given once daily thereafter. In addition, the ketoprofen treatment groups received 2 g ketoprofen intramuscularly once daily for the duration of the antimicrobial therapy. Recovery rates for the non-blind contemporary controls and the blind placebo-controls were 83.7 per cent and 70.7 per cent, respectively. In the non-blind controlled ketoprofen and the placebo-controlled ketoprofen treatment groups, recovery rates were 94.7 per cent and 92.3 per cent, respectively. The odds ratio (OR) of recovery was significantly (P < or = 0.01) high in the placebo-controlled study (OR = 6.75, confidence interval [CI] = 1.45 to 31.4), and high but not significant in the non-blind controlled study (OR = 2.64, CI = 0.53 to 13.10). It was concluded that ketoprofen significantly improved recovery in clinical mastitis in dairy cows.

Animals↗

Retroperitoneal hemorrhage from a ruptured renal artery aneurysm with spontaneous resolution.

Rupture of a renal artery aneurysm is an acute surgical event with a high associated mortality rate. We report an unusual case of acute retroperitoneal hemorrhage from a ruptured renal artery aneurysm that resolved spontaneously with resultant pseudoaneurysm formation. Elective surgical management was performed with a simplified technique involving ligation of the neck of the renal artery aneurysm.

Aneurysm, Ruptured↗

Isolation and structure elucidation of new taxoids from Taxus brevifolia.

An investigation of Taxus brevifolia extracts afforded two taxoids characterized by the A-nortaxol ring system. These were identified as 7,13-dideacetyl-9,10- debenzoyltaxchinin C [1] and 9-deacetyl-9-benzoyl-10-debenzoylbrevifoliol [4]. Structures were elucidated by spectroscopic methods, and in particular by comparison of nmr data with those of taxchinin C and brevifoliol.

Acetylation↗

Characterization of a soybean beta-conglycinin-degrading protease cleavage site.

Protease C1, an enzyme from soybean (Glycine max [L.] Merrill cv Amsoy 71) seedling cotyledons, was previously determined to be the enzyme responsible for the initial degradation of the alpha' and alpha subunits, but not the beta subunit, of beta-conglycinin storage protein. The sizes of the proteolytic products generated by the action of protease C1 suggest that the cleavage sites on the alpha' and alpha subunits of beta-conglycinin may be located in their N-terminal domain, which is not found in the beta subunit of beta-conglycinin. To check this hypothesis, storage proteins from other plant species that are homologous to either the alpha'/alpha or the beta subunit of beta-conglycinin were tested as substrates. As expected, the convicilin from pea (Pisum sativum), a protein homologous to the alpha' and alpha subunits of beta-conglycinin, was digested by protease C1. The vicilins from pea as well as vicilins from adzuki bean (Vigna angularis), garden bean (Phaseolus vulgaris), black-eyed pea (Vigna unguiculata), and mung bean (Vigna radiata), storage proteins that are homologous to the beta subunit of soybean beta-conglycinin, were not degraded by protease C1. Degradation of soybean beta-conglycinin involves a sequential attack of the alpha subunit at multiple sites, culminating in the formation of a stable intermediate of 53.5 kD and a final product of 48.0 kD. The cleavage sites resulting in this formation of the intermediates and final product were determined by N-terminal analysis. These were compared to the known amino acid sequences of the three beta-conglycinin subunits. Results showed these two polypeptides to be generated by proteolysis of the alpha subunit at regions bearing long strings of acidic amino acid residues.

Amino Acid Sequence↗