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Biomedical subjects

H Peng

Publications and source records attributed to H Peng.

At least 73 records · Page 4Linked to original sources

BCL10 gene mutation in lymphoma.

BCL10 is directly involved in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. Wild-type BCL10 promoted apoptosis and suppressed malignant transformation in vitro, whereas truncated mutants lost the pro-apoptotic activity and exhibited gain of function enhancement of transformation. We studied 220 lymphomas for genomic BCL10 mutation by polymerase chain reaction-single-strand conformational polymorphism and DNA sequencing. Nineteen mutations were found in 13 lymphoma specimens, as follows: 8 of 120 (6.7%) mucosa-associated lymphoid tissue (MALT) lymphomas, 4 of 42 (9.5%) follicular lymphomas, and 1 of 23 (4.3%) diffuse large B-cell lymphomas. No mutations were found in 14 mantle cell lymphomas or 21 T-cell lymphomas. High-grade MALT lymphoma tended to show a slightly higher mutation frequency (2 of 25, 8%) than low-grade MALT tumor (6 of 95, 6.3%). Among low-grade gastric MALT lymphoma, mutations were found in 3 of 11 tumors that did not respond to Helicobacter pylori eradication therapy, but none were found in 22 tumors that regressed completely after H pylori eradication. All 14 potentially pathogenic mutations were distributed in the carboxyl terminal domain of BCL10. Deletion accounted for 10 of these mutations; 10 of 14 mutations caused truncated forms of BCL10. Western blot analysis of a mutant case confirmed the presence of truncated BCL10 products of anticipated size. Our results suggest that BCL10 mutation may play a pathogenic role in B-cell lymphoma development, particularly in aggressive and antibiotic unresponsive MALT lymphomas, and may further implicate the biologic importance of the carboxyl terminal of the molecule. (Blood. 2000;95:3885-3890)

Adaptor Proteins, Signal Transducing↗

ARHI is the center of allelic deletion on chromosome 1p31 in ovarian and breast cancers.

In our previous work, we had characterized ARHI as an imprinted putative tumor-suppressor gene in ovarian and breast cancers. ARHI is expressed in primary breast and ovarian cell lines but largely absent from the corresponding malignant tumors. Moreover, the non-imprinted functional allele is typically deleted in malignant cells. Since ARHI had been mapped to 1p31, a common deletion site in breast and ovarian cancer and male germ-cell tumors, in this study, we set out to define precisely the physical location of ARHI at 1p31 and to determine if this location lies within the smallest common region of deletion in breast and ovarian cancers. To this end, we first carried out radiation hybrid mapping of ARHI and surrounding markers, followed by a high-resolution study of loss of heterozygosity at 1p31 in 49 ovarian and breast cancers. Combining a radiation hybrid map and a physical map of the region encompassing ARHI, 3 discrete regions of minimal deletion were found at 1p31 in breast and ovarian cancers. ARHI is the most common deletion region at 1p31. Two other less common regions of deletion were found centromeric to this gene. One of them centered on D1S207 and the other one included and was proximal to D1S488. We also confirmed the preferential loss of non-imprinted functional allele in 7 of 9 tumor specimens. These data support the possibility that ARHI is a tumor-suppressor gene and suggest that additional tumor-suppressor genes may lie proximal to ARHI at 1p31. The data obtained from our study should aid in the identification and characterization of genes in this novel imprinted region.

Breast Neoplasms↗

Expression of alpha-calcitonin gene-related peptide in the enteric nervous system of rat small intestine.

We first detected alpha-calcitonin gene-related peptide (alpha-CGRP) precursor mRNA in the enteric nervous system (ENS) of rat small intestine by reverse transcriptase polymerase chain reaction (RT-PCR). The nucleotide sequence of the RT-PCR product was completely identical to that found in other organs. By in situ hybridization using digoxygenin-labeled alpha-CGRP precursor cRNA probe, we found that antisense probes detected a signal on nerve cell bodies of both submucosal and myenteric plexuses. Our findings indicate that the rat ENS participates in synthesis of alpha-CGRP precursor.

Animals↗

Mutational analysis of Escherichia coli topoisomerase IV. I. Selection of dominant-negative parE alleles.

In order to define regions of ParE, one of the two subunits of topoisomerase IV, that are involved in catalysis during topoisomerization, we developed a selection procedure to isolate dominant-negative parE alleles. Both wild-type parC and mutagenized parE were expressed from a tightly-regulated lac promoter on a moderate-copy plasmid. Mutated parE alleles were rescued from those plasmids that caused IPTG-dependent cell death. The mutant ParE proteins could be divided into two groups when reconstituted with ParC to form topoisomerase IV, those that elicited hyper-DNA cleavage and those that affected covalent complex formation.

Alleles↗

Reconstitution of the KRAB-KAP-1 repressor complex: a model system for defining the molecular anatomy of RING-B box-coiled-coil domain-mediated protein-protein interactions.

The KRAB domain is a 75 amino acid residue transcriptional repression module commonly found in eukaryotic zinc-finger proteins. KRAB-mediated gene silencing requires binding to the corepressor KAP-1. The KRAB:KAP-1 interaction requires the RING-B box-coiled coil (RBCC) domain of KAP-1, which is a widely distributed motif, hypothesized to be a protein-protein interface. Little is known about RBCC-mediated ligand binding and the role of the individual sub-domains in recognition and specificity. We have addressed these issues by reconstituting and characterizing the KRAB:KAP-1-RBCC interaction using purified components. Our results show that KRAB binding to KAP-1 is direct and specific, as the related RBCC domains from TIF1alpha and MID1 do not bind the KRAB domain. A combination of gel filtration, analytical ultracentrifugation, chemical cross-linking, non-denaturing gel electrophoresis, and site-directed mutagenesis techniques has revealed that the KAP-1-RBCC must oligomerize likely as a homo-trimer in order to bind the KRAB domain. The RING finger, B2 box, and coiled-coil region are required for oligomerization of KAP-1-RBCC and KRAB binding, as mutations in these domains concomitantly abolished these functions. KRAB domain binding stabilized the homo-oligomeric state of the KAP-1-RBCC as detected by chemical cross-linking and velocity sedimentation studies. Mutant KAP-1-RBCC molecules hetero-oligomerize with the wild-type KAP-1, but these complexes were inactive for KRAB binding, suggesting a potential dominant negative activity. Substitution of the coiled-coil region with heterologous dimerization, trimerization, or tetramerization domains failed to recapitulate KRAB domain binding. Chimeric KAP-1-RBCC proteins containing either the RING, RING-B box, or coiled-coil regions from MID1 also failed to bind the KRAB domain. The KAP-1-RBCC mediates a highly specific, direct interaction with the KRAB domain, and it appears to function as an integrated, possibly cooperative structural unit wherein each sub-domain contributes to oligomerization and/or ligand recognition. These observations provide the first principles for RBCC domain-mediated protein-protein interaction and have implications for identifying new ligands for RBCC domain proteins.

Amino Acid Motifs↗

Clenbuterol reduces degeneration of exercised or aged dystrophic (mdx) muscle.

Evidence of dystrophic muscle degeneration in the hind limb muscles of young (20-week-old) treadmill-exercised or aged (87-week-old) sedentary mdx mice was greatly reduced by treatment with clenbuterol, a beta(2)-adrenoceptor agonist. Daily treadmill exercise for 10 weeks increased the size of regions within the mdx plantaris but not the soleus or gastrocnemius muscles, in which necrotic muscle fibers or the absence of fibers was observed. Clenbuterol reduced the size of these abnormal regions from 21% of total muscle cross-sectional area to levels (4%) found in sedentary mdx mice. In addition, the muscles obtained from aged clenbuterol-treated mdx or wild-type mice did not display the extensive fibrosis or fiber loss observed in untreated mdx mice. These observations are consistent with a mechanism of dystrophic muscle degeneration caused by work load-induced injury that is cumulative with aging and is opposed by beta(2)-adrenoceptor activation. Optimization of beta(2)-agonist treatment of muscular dystrophy in mdx mice may lead to a useful therapeutic modality for human forms of the disease.

Adrenergic beta-Agonists↗

Clonality analysis of defined cell populations in paraffin-embedded tissue sections by RT-PCR amplification of X-linked G6PD gene.

This paper establishes a method of clonality analysis using the reverse transcription-polymerase chain reaction (RT-PCR) to amplify X-linked G6PD transcripts on defined cell populations microdissected from archival, paraffin-embedded tissue sections. Four known monoclonal low-grade B-cell lymphomas from females who were heterozygous (informative) at the 1131 exonic polymorphic locus of the G6PD gene were used to validate the method. Lymphoma and reactive lesions in each case were separated by microdissection. In order to preserve the intact RNA species in the lesion, sections were digested on the slides before microdissection. A one-step RT-PCR was performed with a single pair of primers, one of which contained a mismatched base adjacent to the polymorphic site, to generate a PvuI cutting site. Successful amplification and allele identification by PvuI digestion were achieved from all RNA samples studied. Three of four samples from non-neoplastic reactive lesions showed two bands with equal intensity, representing transcription of the two alleles of the G6PD gene, while the corresponding tumour samples demonstrated a biased intensity in one allele, indicating monoclonality. To assess the method further, the clonal nature of in situ and invasive breast cancers was examined, along with adjacent normal breast tissue and hyperplastic lesions from three informative females from our archives. Apart from the clusters of normal terminal duct-lobular units, all lesions were monoclonal. This result is in agreement with data derived from other X-linked gene studies and loss of heterozygosity (LOH) analyses of pre-invasive breast disease. The results suggest that the clonality analysis method presented here is simple and reliable, and is therefore potentially applicable in a wide range of pathological conditions.

Breast↗

Significantly different bcl-2 expression profiles in gastric and non-gastric primary extranodal high-grade B-cell lymphomas.

Fifty-five cases of primary extranodal high-grade B-cell non-Hodgkin's lymphoma were investigated for bcl-2 and p53 protein expression as well as for t(14;18) translocations and p53 mutations. Phenotypic and genotypic profiles were compared between tumours of gastric (27 cases) and non-gastric (28 cases) origin. bcl-2 protein expression was significantly lower in gastric (11/27) than in non-gastric (28/28) lymphomas (p<0.0001), while nuclear p53 protein expression did not differ significantly between these two groups. In the stomach, there were no significant differences in either bcl-2 or p53 expression profiles between high-grade lymphomas with (n=14) and without (n=13) evidence of a low-grade component of MALT type. However, secondary high-grade lymphomas showed a significant down-regulation of bcl-2 protein (p<0.0001) and, conversely, an up-regulation of p53 protein (p<0.0001) as compared with their low-grade tumour components. In extranodal high-grade B-cell lymphomas, bcl-2 protein expression was not associated with t(14;18) translocation. Only one gastric lymphoma had a p53 point mutation with potential alteration of the amino acid sequence. These findings indicate that primary gastric high-grade B-cell lymphomas are immunohistologically distinct from primary extranodal high-grade B-cell lymphomas of an origin other than in the stomach.

Biomarkers, Tumor↗

Study on the relationship between plasma homocysteine and acute cerebral vascular disease.

The levels of plasma homocysteine were determined by using high-performance liquid chromatographic method. It was found that plasma homocysteine levels were significantly higher in the patients with stroke than that in the controls. There was no correlation between plasma homocysteine levels and hypertension, smoking, concentrations of blood glucose or hypertriglyceridesemia. It was suggested that hyperhomocysteinemia may be an independent risk factor for acute cerebral vascular disease.

Cerebral Hemorrhage↗

Bulk acoustic wave sensor for herbicide assay based on molecularly imprinted polymer.

A novel molecularly imprinted polymer (MIP) coated bulk acoustic wave (BAW) sensor was fabricated for liquid phases. It can be used as a sensitive portable implement for the assay of 2,4-dichlorophenoxyacetic acid. A logarithmic response relationship between 2.0 x 10(-7) M and 5.0 x 10(-4)M was found. The detection limit was 1.0 x 10(-7) M. Recoveries were 93.2-108.7%. Influencing factors were investigated in detail and optimized.

2,4-Dichlorophenoxyacetic Acid↗

Rapid detection of low levels of Listeria in foods and next-day confirmation of L. monocytogenes.

Outbreaks of foodborne listeriosis caused by Listeria monocytogenes in recent years, and the high mortality rate associated with listeriosis, have raised the need for reliable and rapid detection of the pathogen. A simple, automated method was developed for the detection of Listeria organisms in foods. It consists of a 6-h pre-enrichment step followed by overnight incubation in selective broth at 35 degrees C. Changes in light transmittance in the selective broth are registered continuously by an optical sensor of the BioSys instrument (MicroSys, Ann Arbor, MI), and recorded in the computer. Esculin hydrolysis by listeriae results in black coloration of the media that causes a sharp drop in light transmittance, whereas negative samples remain colorless. Confirmation of L. monocytogenes is carried out only on esculin-positive samples and is completed within 6 h. Detection of 10-50 cells of Listeria inoculated into 25 g of food was confirmed in shell eggs, milk and ground beef. Naturally contaminated raw and ready-to-eat foods were further screened to validate the procedure.

Animals↗

3Beta-hydroxy-6-aza-cholestane and related analogues as phosphatidylinositol specific phospholipase C (PI-PLC) inhibitors with antitumor activity.

6-Aza steroid analogues were synthesized as PI-PLC inhibitors. The most active compound, 3beta-hydroxy-6-aza-cholestane (1) showed potent PI-PLC inhibition (IC50 = 1.8 microM), similar to that of the commercially available steroid analogue U73122 (IC50 = 1-2.1 microM). Compound 1 exhibited significant growth inhibition effects (IC50 = 1.3 microM in each case) against MCF-7 and HT-29 cancer cells in in vitro cell culture. Compound 1 also inhibited the in vitro adhesion and transmigration of HT-1080 fibrosarcoma cells at 2.5 and 5.0 microM, respectively. In vivo, compound 1, at 1 mg/kg/day, reduced the volume of MCF-7 tumors in xenograft models, without weight loss in mice. Structure activity relationships of this series of compounds revealed that a hydrophobic cholesteryl side chain, 3beta-hydroxy group and a C-6 nitrogen containing a hydrogen atom at position-6 are crucial for activity. N-Maleic amidoacid derivative 11 also exhibited weak inhibition (IC50 = 16.2 microM).

Animals↗

Steroidal derived acids as inhibitors of human Cdc25A protein phosphatase.

A group of steroidal derived acids were synthesized and found to be human Cdc25A inhibitors. Their potency ranged from 1.1 to > 100 microM; the best ones compare very favorably with that of the novel cyano-containing 5,6-seco-cholesteryl acid 1 (IC50=2.2microM) reported by us recently (Peng, H.; Zalkow, L. H.; Abraham, R. T.; Powis, G. J. Med. Chem. 1998, 41, 4677). Structure-activity relationships of these compounds revealed that a hydrophobic cholesteryl side chain and a free carboxyl group are crucial for activity. The distance between these two pharmacophores is also important for the potency of these compounds. Several of the compounds showed selective growth inhibition effects in the NCI in vitro cancer cell line panel.

Acids↗

A semi-parametric hybrid neural model for nonlinear blind signal separation.

Nonlinear blind signal separation is an important but rather difficult problem. Any general nonlinear independent component analysis algorithm for such a problem should specify which solution it tries to find. Several recent neural networks for separating the post nonlinear blind mixtures are limited to the diagonal nonlinearity, where there is no cross-channel nonlinearity. In this paper, a new semi-parametric hybrid neural network is proposed to separate the post nonlinearly mixed blind signals where cross-channel disturbance is included. This hybrid network consists of two cascading modules, which are a neural nonlinear module for approximating the post nonlinearity and a linear module for separating the predicted linear blind mixtures. The nonlinear module is a semi-parametric expansion made up of two sub-networks, one of which is a linear model and the other of which is a three-layer perceptron. These two sub-networks together produce a "weak" nonlinear operator and can approach relatively strong nonlinearity by tuning parameters. A batch learning algorithm based on the entropy maximization and the gradient descent method is deduced. This model is successfully applied to a blind signal separation problem with two sources. Our simulation results indicate that this hybrid model can effectively approach the cross-channel post nonlinearity and achieve a good visual quality as well as a high signal-to-noise ratio in some cases.

Algorithms↗

Comparison of two group counseling approaches to enhancing confidence in planning careers by undecided Taiwanese college women.

This is a report of research comparing two approaches to enhance the career confidence of undecided female college students. 30 women who requested enrollment in career counseling were assigned to two counseling groups (a cognitive reconstructing intervention group and a career decision-making skills training group) and one no-treatment control group based on time of request. After participating in the two career counseling groups for eight sessions in a month, the female college students rated their mean confidence as increased over that of the no-treatment group. Analysis indicated that the indecisive female college students benefitted from career group counseling with an emphasis on self-efficacy and that the cognitive reconstructing intervention was more effective.

Adult↗

Evaluation of a distance education course in students' decision-making and beliefs about careers.

To assess the influence of a distance course on careers in students' career decision-making and beliefs, 178 distance education college students in the Open University in Taiwan completed the Career Decision Scale, the Career Beliefs Checklist, and a demographic sheet. Unlike most prior research, the course was not associated with career decision-making and beliefs of the students, but students mentioned that career beliefs influenced their decision-making. Three-way multivariate analysis of covariance showed a main effect for age groups on career indecision. On a follow-up questionnaire to which 143 of the same subjects responded, the students indicated their concern about specific factors in career decision-making. The research findings have important implications for the redesign of the career education course for adults and for research.

Adult↗

[Influence of genetic background of photoperiodic response on expression of short photoperiod sensitive male sterility in rice].

The photoperiodic response of F1 and its parents was analyzed, and the photoperiodic response and short photoperiod sensitive male sterility of F2 progenies were studied in this paper. The results showed that the strong response was dominant over the weak response to photoperiod. The photoperiodic response of plants with short photoperiod sensitive male sterility in F2 was above medial degree(the rate of heading acceleration > 15%). Photoperiodic response showed a positive correlation with short photoperiod sensitive male sterility. The main sterility genes of Yid1s and Yid2s were allelism. It can be inferred that the short photoperiod sensitive male sterile gene might be expressed upon the presence of the photoperiodic response genes, and that the short photoperiod sensitive male sterility of plants with the same genes could differ in their reproductive expressions, not because of the changes of the genes, but the difference in genetic backgrounds of photoperiodic response.

Fertility↗