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Biomedical subjects

R Chen

Publications and source records attributed to R Chen.

At least 487 records · Page 27Linked to original sources

Initial enlargement of the opposite pupil as a false localising sign in intraparenchymal frontal haemorrhage.

Ipsilateral third nerve palsy with early pupillary enlargement is an important sign of transtentorial herniation from a supratentorial mass lesion. A case of frontal, intraparenchymal haemorrhage is reported in which the first ocular manifestation of transtentorial herniation was enlargement of the contralateral pupil. The ipsilateral pupil dilated only after complete oculomotor palsy of the contralateral eye. After partial frontal lobectomy and removal of blood clot, the ipsilateral third nerve recovered before the contralateral third nerve. Clinical findings localised the contralateral third nerve lesion to an extra-axial site. The possible mechanisms of contralateral third nerve compression are discussed. This seems to be the first example of pupillary enlargement as a false localising sign from a contralateral, supratentorial, intraparenchymal mass lesion.

Adult↗

Combination of hematopoietic growth factors containing IL-3 induce acute myeloid leukemia cell sensitization to cycle specific and cycle non-specific drugs.

Laboratory studies have suggested that hematopoietic growth factors (GF), combined with cytosine-arabinoside (Ara-C) can enhance cytotoxic effects of this agent against acute myeloid leukemia (AML) cells. While clinical trials based on this growth factor/chemotherapy combination (GF/CT) are progressing with discordant results, further information regarding the underlying mechanisms have been reported supporting this rationale and requiring additional investigation. To assess the role of cytokinetic changes in the GF/CT strategy and to evaluate if chemotherapeutic agents regimens other than Ara-C, when combined with GF, can enhance their cytotoxic effects, we have primed AML blasts with two cytokine combinations and then exposed these cells to the S-phase specific agent Ara-C as well as to the phase non-specific drug daunorubicin (DNR) and to the alkylating agent 4-hydroperoxycyclophosphamide (4-HC). The two cytokine combinations used for priming AML blasts were: (i) interleukin-3 (IL-3) + granulocyte-macrophage colony-stimulating factor (GM-CSF) + granulocyte colony-stimulating factor (G-CSF); and (ii) GM + G-CSF. Cytokinetic analysis in ten AML samples and clonogenic growth of leukemic colonies (CFU-L) in methylcellulose were used to detect proliferative and cytotoxic effects on AML samples. We report that in AML clonogenic cell growth can be stimulated by cytokines in 50% of the samples (4/8), and that Ara-C sensitization clearly occurs in two out of these four samples. Among the different cytokine combinations tested, the one containing IL-3 was the most effective through a cytokinetic mechanism consistent with recruitment (averaged G0 decrease p = 0.04; S-phase increase p = 0.005). Furthermore we observed increased cytotoxicity also to the phase non-specific drugs DNR and 4-HC, which may be mediated by other mechanisms recently described. We conclude that GF/CT combinations may also be beneficial in regimens containing drugs other than Ara-C, used for AML treatment, including bone marrow transplantation conditioning regimens.

Antineoplastic Agents↗

Detection of keratinocyte growth factor (KGF) transcripts from normal human and archival canine benign prostatic hyperplastic tissues.

This study examined the expression of keratinocyte growth factor (KGF) gene in human and canine prostatic tissues. KGF transcript was detected in normal human prostatic tissues by reverse transcription and polymerase chain reactions (RT-PCR). PCR-generated human KGF complementary DNA (cDNA) clone was confirmed by restriction enzyme digestion analysis and partial DNA sequencing. Expression of KGF in archival canine benign prostatic hyperplastic tissues was also examined. In a pilot experiment, RNAs isolated from formalin-fixed (FF) and formalin-fixed and paraffin-embedded (FFPE) canine prostatic tissues were shown to be of sufficient quality to permit amplification of KGF mRNA by RT-PCR. The transcript of a housekeeping gene, glucose-6-phosphate dehydrogenase (G6PD), was detected by RT-PCR indicating the quality of RNAs to be more than adequate for RNA expression analysis. Later, total RNA from two archival canine FF prostate tissue types, benign prostatic hyperplasis and mild glandular hyperplasia, were used to amplify canine KGF transcripts. Southern hybridization analysis using rat and human KGF cDNAs as probes confirmed the fidelity of the amplified PCR product and it was indeed canine KGF.

Animals↗

[Effect of some drugs on electroacupuncture analgesia and cytosolic free Ca2+ concentration of mice brain].

In this paper, the effects of some analgesic drugs such as corydalis yanhusuo, Angelica dahurica and Analginum on electroacupuncture analgesic function were studied. In the meantime, the concentrations of cytosolic free Ca2+ ([Ca2+]i) in mice hypothalamus (HT) and periaqueductual grey (PAG) were determined by use of the fluorescence dye Fura-2/AM and AR-CM cation measurement system. The results showed that Corydalis yanhusuo obviously strengthened the analgesic function produced by electroacupuncture. Besides, the [Ca2+]i in the two brain regions of mice in these analgesic experiments with electroacupuncture and Corydalis yanhusuo were all decreased (compared with saline control group, P < 0.01), In the same experimental condition, the [Ca2+]i in Angelica dahurica group and Analginum group has no significant difference compared with the control group, the analgesic mechanisms may be different from that of electroacupuncture and Corydalis yanhusuo.

Acupuncture Analgesia↗

[Study on polymorphism of ribosomal RNA gene in Chinese Hans and Yis].

In the secondary constriction region of the short arm of human group D and group G acrocentric chromosomes there are tandemly repeated sequences of transcriptable segments and non-transcriptable spacers of rRNA genes. In the non-transcriptable spacer segments there is a polymorphic region with length variation. This paper reports the results obtained when the BamHI digested products of genomic DNA from 36 cases of Han nationality and those from 40 cases of Yi nationality were probed with a cDNA subprobe, pA(BE), which corresponds to the downstream one third of the 28S rRNA gene and is 1.6kb long with BamHI and EcoRI restriction sites at its two terminal respectively, using Southern blotting and molecular hybridization techniques. A total of 10 different restriction fragments were detected. Four fragments (7.9, 4.9, 4.0 and 1.2 kb) were seen in all subjects tested and the frequencies of six other polymorphic fragments in Hans and Yis (10.0, 9.4, 8.5, 6.7 6.0 and 3.0 kb) showed no significant difference when compared to each other. From the 10 different patterns of combination of restriction fragments four of them (1HY, 2HY, 3HY and 4HY) were detected in both Hans and Yis with no significant difference between their respective frequencies. Four other patterns (5H, 6H, 7H and 8H) were only seen in Hans with individual frequencies not high enough to be statistically significant. However, the statistical test for the combined frequencies of these four patterns showed highly significant difference between Hans and Yis (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

China↗

Expression cloning of a human corticotropin-releasing-factor receptor.

Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. We report here the cloning of a cDNA coding for a CRF receptor from a human corticotropic tumor library. The cloned cDNA encodes a 415-amino acid protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive intestinal peptide/growth hormone-releasing hormone subfamily of G protein-coupled receptors. The receptor expressed in COS cells binds rat/human CRF with high affinity (Kd = 3.3 +/- 0.45 nM) and specificity and is functionally coupled to adenylate cyclase. The CRF antagonist alpha-helCRF-(9-41) inhibits the CRF-stimulated increase in intracellular cAMP. Northern blot analysis reveals that the CRF receptor is expressed in the rat pituitary and brain as well as in the mouse AtT20 corticotropic cells. We also describe an alternatively spliced form of the receptor which includes an insert of 29 amino acids in the first intracellular loop.

1-Methyl-3-isobutylxanthine↗

The ATP4- receptor-operated channel (P2Z class) of human lymphocytes allows Ba2+ and ethidium+ uptake: inhibition of fluxes by suramin.

It is now recognized that extracellular ATP can open a receptor-operated ion channel in a variety of cell types. In human lymphocytes this P2Z purinergic channel conducts Na+, K+, Rb+, Li+, and Ca2+ but its permeability to larger cations is not known. Fluorometric measurements were used to show that ATP4- induced the entry of Sr2+ (87 Da) and Ba2+ (137 Da) into human lymphocytes loaded with fura-2. Flow cytometry was used to show that ATP4- induced the entry of ethidium+ (314 Da) but that the larger propidium2+ cation (414 Da) was excluded. ATP(4-)-induced entry of both Ba2+ and ethidium+ showed features previously demonstrated for smaller cation permeants: (i) inhibition by amiloride analogs, (ii) sigmoid dependence of flux on ATP concentrations, and (iii) inhibition by extracellular Na+ ions. Specific inhibitors of L-type voltage-gated Ca2+ channels (nisoldipine and diltiazem) had no effect on ATP(4-)-induced Ba2+ influx. Suramin and reactive blue 2, which are recognized antagonists of ATP-operated purinergic receptors in other tissues, inhibited ATP-induced uptake of ethidium+ in lymphocytes with K1/2 of 61 and 69 microM, respectively. However, hexamethylene amiloride was a more potent inhibitor of ATP-induced ethidium+ uptake with a K1/2 of 13 microM. These data show that the ATP4- receptor-operated channel of human lymphocytes allows influx of cations as large as Ba2+ or ethidium+ and that this influx is inhibited by suramin and reactive blue 2.

Adenosine Triphosphate↗

Nuclear matrix proteins in normal and breast cancer cells.

The progression from normal breast epithelium to a malignant phenotype may depend on changes in genetic events as well as failure of host mechanisms. Intermediate biomarkers are needed to more effectively identify malignant progression as well as to develop the potential for more specific treatments and prevention strategies. The nuclear matrix is the RNA-protein network which forms the skeleton of the nucleus and participates in DNA organization as well as multiple cellular functions. Nuclear matrix proteins have been demonstrated to be tissue and cell type specific as well as to reflect the state of cell differentiation and/or transformation. We prepared nuclear matrices from normal and cancer breast tissue from 10 patients with infiltrating ductal carcinoma of the breast as well as the MCF-10 mortal, immortal, and transfected breast cell lines. Nuclear matrices derived from normal human breast tissue and tumor tissue share common nuclear matrix proteins as well as demonstrate specific changes which appear to occur with the acquisition of the cancer phenotype. The MCF-10 cell lines demonstrate a phenotype that is intermediate between the normal and cancer tissue. These data suggest that the nuclear matrix may be an important biomarker in the pathogenesis of breast cancer.

Aged↗

Enantioselective detoxication of optical isomers of glycidyl ethers.

The detoxication of the enantiomers of glycidyl 4-nitrophenyl ether (GNPE), (-)-(R)- and (+)-(S)-GNPE, and glycidyl 1-naphthyl ether (GNE), (-)-(R)- and (+)-(S)-GNE, by rat liver glutathione transferase and epoxide hydrolase was studied. Enantioselectivity was observed with both enzymes favoring the (R)-isomers as determined by the formation of conjugate, diol, and remaining substrate measured by HPLC. Enantiomers of GNE were detoxified by cytosolic epoxide hydrolase but those of GNPE were not. Substantial nonenzymatically formed conjugates of enantiomers of GNPE were detected showing (S)-GNPE the more reactive of the pair.

Animals↗

Analysing post-alarm data in a monitoring system in order to accept or reject the alarm.

In a disease monitoring system embracing several diseases and communities, alarms indicating a significant increase in disease incidence will frequently occur even though the false alarm rate has been set quite low. An approach is presented by which an alarm is determined as either confirmed or rejected according to data observed subsequent to the alarm. The suggested procedure is expected to weed out a substantial proportion (say about 75 per cent) of the false alarms at the expense of some delay in detecting a true alarm.

Cluster Analysis↗

Coincident indices of exons and introns.

In this paper, the coincident index, proposed by W. F. Friedman in cryptology, is made use of in DNA sequence analysis and exon prediction. The coincident index of exons exceeds that of introns by many times, and is mainly affected by window length, which is correlated negatively with the coincident index. An optimal exon prediction scheme was obtained by experimental analysis with an orthogonal table. Besides exons, many other special sites such as tandem repeats can be identified by using the coincident index approach. The application of this approach to the ARV-2 (AIDS associated retrovirus 2) genome found three new possible coding regions and some unusual base composition regions which are probably related to definite biological functions.

Base Composition↗

The genotoxicity of enantiomeric aliphatic epoxides.

The (R)- and (S)-optical isomers of 9 epoxides, benzyloxymethyloxirane, epichlorohydrin, glycidol, glycidyl 3-nitrobenzenesulfonate, glycidyl 4-nitrobenzoate, glycidyl tosylate, styrene oxide, glycidyl 1-naphthyl ether and glycidyl 4-nitrophenyl ether, have been compared for their in vivo and in vitro genotoxicity. The in vitro short-term test employed was the Ames mutagenicity assay with Salmonella strain TA100. The in vivo tests were chromosomal aberrations (CA) as well as sister-chromatid exchange (SCE) in bone-marrow cells of mice following intraperitoneal administration of these epoxides. Differences in mutagenicity between isomers were established with TA100 for all the compounds. While 13 of the isomers were genotoxic compared to a negative control by CA measurements, only in the case of glycidyl 4-nitrobenzoate could a significant difference be found between isomers by this test. However, with SCE evaluations, differences were detected between the (R)- and (S)-isomers for all the pairs of compounds with the exception of those for benzyloxymethyloxirane and glycidyl 4-nitrophenyl ether. At least in part, differences in the patterns of genotoxicity among compounds can be related to their differences in reaction pathways.

Animals↗

Reflex responses in upper limb muscles to cutaneous stimuli.

Cutaneous reflexes in the upper limb were elicited by stimulating digital nerves and recorded by averaging rectified EMG from proximal and distal upper limb muscles during voluntary contraction. Distal muscles often showed a triphasic response: an inhibition with onset about 50 ms (I1) followed by a facilitation with onset about 60 ms (E2) followed by another inhibition with onset about 80 ms (I2). Proximal muscles generally showed biphasic responses beginning with facilitation or inhibition with onset at about 40 ms. Normal ranges for the amplitude of these components were established from recordings on 22 arms of 11 healthy subjects. An attempt was made to determine the afferent fibers responsible for the various components by varying the stimulus intensity, by causing ischemic block of larger fibers and by estimating the afferent conduction velocities. The central pathways mediating these reflexes were examined by estimating central delays and by studying patients with focal lesions.

Adult↗

A tissue-specific enhancer confers Pit-1-dependent morphogen inducibility and autoregulation on the pit-1 gene.

Pit-1 is a tissue-specific POU domain factor obligatory for the appearance of three cell phenotypes in the anterior pituitary gland. Expression of the pit-1 gene requires the actions of a cell-specific 390-bp enhancer, located 10 kb 5' of the pit-1 transcription initiation site, within sequence that proves essential for effective pituitary targeting of transgene expression during murine development. The enhancer requires the concerted actions of a cell-specific cis-active element, Pit-1 autoregulatory sites, and atypical morphogen response elements. Pituitary ontogeny in the Pit-1-defective Snell dwarf mouse reveals that pit-1 autoregulation is not required for initial activation or continued expression during critical phases of Pit-1 target gene activation but, subsequently, is necessary for maintenance of pit-1 gene expression following birth. A potent 1,25-dihydroxyvitamin D3-responsive enhancer element defines a physiological site in which a single nucleotide alteration in the sequence of core binding motifs modulates the spacing rules for nuclear receptor response elements. Unexpectedly, the major retinoic acid response element is absolutely dependent on Pit-1 for retinoic acid receptor function. On this DNA element, Pit-1 appears to function as a coregulator of the retinoic acid receptor, suggesting an intriguing linkage between a cell-specific transcription factor and the actions of morphogen receptors that is likely to be prototypic of mechanisms by which other cell-specific transcription factors might confer morphogen receptor responsivity during mammalian organogenesis.

Animals↗