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Biomedical subjects

Y Peng

Publications and source records attributed to Y Peng.

At least 145 records · Page 8Linked to original sources

Localization of BRCA1 and a splice variant identifies the nuclear localization signal.

Inherited mutations in BRCA1 confer susceptibility to breast and ovarian neoplasms. However, the function of BRCA1 and the role of BRCA1 in noninherited cancer remain unknown. Characterization of alternately spliced forms of BRCA1 may identify functional regions; thus, we constructed expression vectors of BRCA1 and a splice variant lacking exon 11, designated BRCA1 delta 672-4095. Immunofluorescence studies indicate nuclear localization of BRCA1 but cytoplasmic localization of BRCA1 delta 672-4095. Two putative nuclear localization signals (designated NLS1 and NLS2) were identified in exon 11; immunofluorescence studies indicate that only NLS1 is required for nuclear localization. RNA analysis indicates the expression of multiple, tissue-specific forms of BRCA1 RNAs; protein analysis with multiple antibodies suggests that at least three BRCA1 isoforms are expressed, including those lacking exon 11. The results suggest that BRCA1 is a nuclear protein and raise the possibility that splicing is one form of regulation of BRCA1 function by alteration of the subcellular localization of expressed proteins.

3T3 Cells↗

HRS/SRp40-mediated inclusion of the fibronectin EIIIB exon, a possible cause of increased EIIIB expression in proliferating liver.

Serine-arginine (SR)-rich proteins are believed to be important in mediating alternative pre-mRNA splicing. HRS/SRp40 expression is elevated in liver cell proliferation during development, regeneration, and oncogenesis. We tested whether HRS expression correlates with the appearance of alternatively spliced fibronectin transcripts during liver growth. HRS was highly expressed during the proliferative phase of liver development, correlating with expression of the fibronectin EIIIB alternative exon. In regenerating liver, HRS protein was induced in a time course consistent with the observed increase in fibronectin transcripts containing the EIIIB exon, particularly in nonparenchymal liver cells. Furthermore, in an in vivo assay, HRS, and not other SR proteins, directly mediated EIIIB exon inclusion in the fibronectin transcript. This alternative splicing was dependent on a purine-rich region within the EIIIB exon to which HRS specifically bound. We have established that HRS has the potential to contribute to the regulation of fibronectin pre-mRNA splicing during liver growth. Changes in fibronectin forms may be important in modifying liver architecture during the proliferative response, thus providing a potential mechanism by which SR proteins may participate in cellular growth control.

Alternative Splicing↗

Biotransformation of compactin to pravastatin by Actinomadura sp. 2966.

Actinomadura sp. strain 2966 can effectively convert compactin to pravastatin. The degree of conversion observed was 65% to 78% of compactin added and 65% to 88% of compactin taken up, depending on the concentration of compactin and duration of the experiment. Increasing the compactin concentration resulted in a higher final pravastatin concentration especially when compactin was added intermittently. Higher glucose concentrations had no effect on the bioconversion although uptake of compactin was inhibited. The conversion was linear over 16 hours. The system requires no induction and thus appears to be different from previously studied hydroxylases from actinomycetes.

Actinomycetaceae↗

[Evaluating clinical significance of tumor necrosis factor-alpha and hydroxyproline in blood of patients with active pulmonary tuberculosis].

OBJECTIVE: To evaluate the clinical significance of tumor necrosis factor-alpha (TNF-alpha) and hydroxyproline (HYP) in blood of patients with active pulmonary tuberculosis (APT). METHOD: Contents of TNF-alpha and HYP in blood of 28 patients with APT and 17 normal subjects were determined with enzyme-linked immunosorbent assay and ultraviolet spectrophotometer respectively. RESULT: It was found that the concentrations of TNF-alpha and HYP in patients with APT before antituberculosis treatment were obviously higher than those of the normal subjects (192.85 +/- 37.14 ng/L vs 89.36 +/- 23.18 ng/L and 4.96 +/- 1.13 mg/L vs 1.64 +/- 0.33 mg/L respectively, all P < 0.001) and those who received 3- month anti-tuberculosis treatment (192.65 +/- 37.14 ng/L vs 112.50 +/- 44.93 ng/L and 4.96 +/- 1.13 mg/L vs 2.17 +/- 0.39 mg/L respectively, all P < 0.001). TNF-alpha level was significantly correlated with HYP (r = 0.5132, P < 0.001). CONCLUSION: The results indicate that TNF-alpha might play an important role in inducing pulmonary tissue damage of APT, and the lowering of HYP content in blood might indicate that pulmonary tuberculosis is recovering from active stage.

Adolescent↗

[Effects of the double chamber intra-aortic balloon pumping on the renal circulation].

The effects of the double chamber intra-aortic balloon (DIAB) and the single chamber intra-aortic balloon (SIAB) on the hemodynamic parameters in the kidney were studied. No negative effect of both cases was observed. Before and after removing the renal nerve system, the DIAB was used and the results had been compared. The pulse produced by pumping activized the renal nerve system and reduced the renal vascular resistance. Therefore the reduction of the renal vascular resistance is an important reason for increasing the renal blood flow during intra-aortic balloon pumping.

Animals↗

[Analysis of chromosome karyotype of Lycium chinense Mill].

The chromosome karyotypes of wild Lycium chinese and its cultivated breeds for vegetable have been studied. The Chromosome 12 of both has a satellite. The former, with 24 chromosomes and 1B karyotype, is a diploid and its karyotype formula is 2n = 2x = 24 = 18m + 6sm. The chromosome number of the latter is 48. As a tetrploid, it has 2B karyotype and a karyotype formula 2n = 4x = 48 = 36m + 12sm.

Chromosomes↗

Early versus deferred zidovudine monotherapy: impact on AIDS-free time and survival in the multicenter AIDS cohort study.

The objective of this study was to compare the time to AIDS and to death between men receiving zidovudine therapy before or not before the diagnosis of AIDS. For the time to AIDS comparison, 821 men receiving zidovudine therapy before the diagnosis of AIDS were pair matched with men who did not receive zidovudine therapy until after diagnosis on their CD4 cell count (+/- 75 cells/mm3), haemoglobin level (+/- 0.75 g/dl), number of clinical symptoms and study visit at the time of initiation of zidovudine therapy and were monitored for a median of 2.08 years. For the time to death comparison, 186 men who received zidovudine therapy prior to AIDS diagnosis were pair matched on the same variables to men who received zidovudine therapy only after the AIDS diagnosis, and were monitored for a median of 2.88 years. Only men with < 350 CD4 cells/mm3 who received zidovudine therapy prior to AIDS diagnosis remained AIDS free significantly longer than their pair match who did not (P < 0.0001). The median extension of time to AIDS was 0.61 years for men with < 200 CD4 cells/mm3 and 1.13 years for men with 200-349 CD4 cells/mm3. Cox regression analysis showed a significantly increased time to AIDS for the men with < 350 CD4 cells/mm3, both before and after adjustment for the use of prophylactic drugs against Pneumocystis carinii pneumonia. No difference was seen in the time to death between men receiving zidovudine therapy before or only after AIDS diagnosis. Zidovudine treatment of asymptomatic HIV-1-infected men provides significant benefit to men with < 350 CD4 cells/mm3 by extending AIDS-free time, but does not extend survival. The analytical technique used is applicable to other observational studies of treatment.

Acquired Immunodeficiency Syndrome↗

[Human lens epithelial cells culture in vitro].

PURPOSE: To provide a simple and rapid procedure to culture human len epithelial cells in vitro. METHODS: Specimens of capsule lentils were isolated from lens by microscissors. They were cut into small segments and then directly implanted into basks(culture bottles). The tissue pieces were cultured in a incubation at 37 degrees C with PR1640 until attached cells reached confluence. The len epithelium were passaged by tropism. RESULTS: Len epithelial cells usually appeared after 4 days in incubation. The cells growed rapidly in a way of attachments. CONCLUSION: Len epithelial cells were easily cultured with our method. The procedure is simple, rapid and highly successful.

Cell Culture Techniques↗

Optical resolution of DL-alanine by using immobilized Aspergillus oryzae cells.

Mycelium pellets with diameters of 1-2 mm and containing abundant aminoacylase were obtained by the liquid fermentation of Aspergillus oryzae 3042. By the cross-linking method with reagents of gelatin and formaldehyde, the immobilized A. oryzae cells (IAC) were prepared with much higher activity and reactive properties. The effects of factors on enzymatic activity of IAC were investigated. When substrate concentration was less than 0.15 mol/L, the Michaelis-Menten mechanism was suitable for this reaction.

Alanine↗

Cyclopia in one of discordant twins: a case report.

Cyclopia is an uncommon congenital anomaly resulting from arrest of the development of the anterior end of the neural plate. It is always associated with abnormalities of the brain. Cyclopia has never been reported in one twin only. In this report, we describe a case of cyclopia in a female infant with normal karyotype who was one of discordant twins. The infant died perinatally. The parents were healthy and not sanguineously related. Prenatal imaging studies revealed cyclopia, holoprosencephaly and hypognathia. Postmortem examinations revealed one orbit, one eyeball and absence of the nose. The central nervous system included rudimentary cerebral hemispheres with fusion of the two lateral ventricles and the third ventricle forming a single large cavity. The superior aspect of each cerebral hemisphere consisted of only a transparent membrane. The olfactory bulb nad tract was absent. The optic nerves were not identified.

Adult↗

Detection of minimal residual disease in leukemia using polymerase chain reaction and restriction analysis.

OBJECTIVE: To investigate the relationship between the clinical outcome of childhood acute lymphoblastic leukemia and the status of minimal residual disease after termination of therapy. METHODS: A total of 18 children with acute lymphoblastic leukemia were studied. Eleven cases were treated with chemotherapy, the other 7 with autologous peripheral blood stem cell transplantation (ABSCT) or autologous bone marrow transplantation (ABMT). The outcome of the 18 patients was obtained by clinical follow-up. Minimal residual disease was detected by means of the polymerase chain reaction (PCR) and restriction analysis. RESULTS: Minimal residual disease was detected in 9 patients after completion of therapy. Three out of the 9 patients relapsed within 3 to 6 months. Among the other 9 patients with no detectable minimal residual disease, no one relapsed. CONCLUSIONS: PCR detection of minimal residual disease after termination of therapy can identify patients at risk for relapse in future. Minimal residual disease that cannot be detected after termination of therapy may be one of the important factors for long-term disease-free survival.

Adolescent↗

Ryanodine-sensitive component of calcium transients evoked by nerve firing at presynaptic nerve terminals.

Whether Ca2+ released from stores within the presynaptic nerve terminals also contributes to the Ca2+ elevation evoked by action potentials was tested in intact bullfrog sympathetic ganglia. Intraterminal Ca2+ transients (Delta[Ca2+]i) were evoked by electrical shocks to the presynaptic nerves at 20 Hz and were monitored by fura-2 fluorimetry. Ca2+ released through intraterminal ryanodine-sensitive channels accounted for 46% of the peak Ca2+ elevation. Moreover, in half of the terminals when intraterminal release was blocked by ryanodine, Delta[Ca2+]i reached a plateau at 200 +/- 24 nM. Because 20 Hz is a frequency favorable for the release of a neuropeptide, luteinizing hormone releasing hormone (LHRH) from these presynaptic nerve terminals, and because the threshold level for LHRH release is 186 nM, intraterminal Ca2+ release during nerve firing is likely to play a major role in regulating LHRH release. The intraterminal ryanodine channels were facilitated by caffeine as in other tissue. The releasable ryanodine-sensitive store could elevate the intraterminal [Ca2+] by an amount as high as 1.6 microM at a rate as fast as 250 nM/sec. The store could be refilled within 100 sec after a maximal discharge of its content by 20 Hz firing. Oscillation of [Ca2+]i evoked by 20 Hz nerve firing occurred in normal Ringer solution, in ryanodine, and in caffeine with a periodicity of approximately 10 sec. Besides the facilitatory effects on the ryanodine-sensitive channels, caffeine also had inhibitory effects on Delta[Ca2+]i via its action on a different process.

Animals↗

Longitudinal relation between smoking and white blood cells.

Higher white blood cell counts in smokers compared with nonsmokers have been well documented, but the longitudinal relation between changes in smoking and changes in white blood cells has not been well described. Since 1984, data have been collected semiannually by the Multicenter AIDS Cohort Study (MACS), a four-center prospective cohort study of acquired immunodeficiency syndrome (AIDS) in homosexual men. The study population includes 2,435 participants who were human immunodeficiency virus (HIV) seronegative as of September 1994 and who contributed 20,918 person-visits for this analysis. For individuals who modified their smoking behavior, changes in white blood cell counts occurred primarily during the first 6 months following changes in the amount of cigarettes smoked. Among former smokers who resumed smoking, the extent of the increase in white blood cell count depended on the number of cigarettes smoked. Specifically, increases of 241, 340, and 740 cells/microliter were observed for smokers who resumed smoking < 1, 1 to < 2, and > or = 2 packs/day, respectively. Conversely, smokers who quit smoking had a decrease of white blood cell count: -32, -629, and -1,122 cells/microliter for men who previously smoked < 1, 1 to < 2, and > or = 2 packs/day, respectively. Long-term ex-smokers, however, still had higher white blood cell counts than did never smokers. There was a high within-individual correlation of white blood cell count in persons who reported a consistent level of smoking (i.e., average correlations between two white blood cell counts 6 years apart were 0.51 for never smokers, 0.48 for ex-smokers, 0.56 for men who smoked < 1 pack/day, and 0.43 for men who smoked > or = 1 pack/day). These analyses indicate an acute effect of changes in smoking on changes in white blood cell count, a residual effect of having been a smoker, and high long-term tracking for white blood cell count.

Adult↗

Generation of an integrated transcription map of the BRCA2 region on chromosome 13q12-q13.

An integrated approach involving physical mapping, identification of transcribed sequences, and computational analysis of genomic sequence was used to generate a detailed transcription map of the 1. 0-Mb region containing the breast cancer susceptibility locus BRCA2 on chromosome 13q12-q13. This region is included in the genetic interval bounded by D13S1444 and D13S310. Retrieved sequences from exon amplification or hybrid selection procedures were grouped into physical intervals and subsequently grouped into transcription units by clone overlap. Overlap was established by direct hybridization, cDNA library screening, PCR cDNA linking (island hopping), and/or sequence alignment. Extensive genomic sequencing was performed in an effort to understand transcription unit organization. In total, approximately 500 kb of genomic sequence was completed. The transcription units were further characterized by hybridization to RNA from a series of human tissues. Evidence for seven genes, two putative pseudogenes, and nine additional putative transcription units was obtained. One of the transcription units was recently identified as BRCA2 but all others are novel genes of unknown function as only limited alignment to sequences in public databases was observed. One large gene with a transcript size of 10.7 kb showed significant similarity to a gene predicted by the Caenorhabditis elegans genome and the Saccharomyces cerevisiae genome sequencing efforts, while another contained a motif sequence similar to the human 2',3' cyclic nucleotide 3' phosphodiesterase gene. Several retrieved transcribed sequences were not aligned into transcription units because no corresponding cDNAs were obtained when screening libraries or because of a lack of definitive evidence for splicing signals or putative coding sequence based on computational analysis. However, the presence of additional genes in the BRCA2 interval is suggested as groups of putative exons and hybrid selected clones that were transcribed in consistent orientations could be localized to common physical intervals.

BRCA2 Protein↗

Projecting disease when death is likely.

Projection disease incidence, prevalence, and net morbidity is often needed when individuals are likely to die, either disease free or after the disease has developed. Examples of this include remission of cancer or heart disease in elderly people who can die from these or other causes and occurrence of a particular acquired immune deficiency syndrome illness in human immunodeficiency virus type 1 (HIV-1) disease. Death is not an ancillary event but, rather, indicates either and end to disease morbidity or an end to risk to ever develop the disease. Thus, time to disease survival analyses that censor disease-free individuals at death can produce misleading results. The paper describes several useful quantifications of disease and death for this setting. A paradigm that utilizes Kaplan-Meier functions to estimate these quantities is introduced. The approach anchors on a four-stage disease/death model: stage A, living without disease; stage B, dead without ever developing disease; stage C, developed the disease and living; and stage D, dead after developing the disease. An application is made to projecting cytomegalovirus disease in a cohort of HIV-1-infected users of zidovudine and Pneumocystis prophylaxis from the Multicenter AIDS Cohort Study (MACS) during 1989-1993. At 3 years after a CD4+ count below 100/microliters, a man had an 18.7%, 46.3%, 5.3% or 29.9% chance, respectively, to be in stage A, B, C, or D. This man, on average, had 0.28 years of cytomegalovirus morbidity during these 3 years.

AIDS-Related Opportunistic Infections↗

Survival from early, intermediate, and late stages of HIV infection.

OBJECTIVE: To estimate expected survival time among homosexual men infected with the human immunodeficiency virus type 1 (HIV-1) by (1) the calendar period before (1985-1988) and after (1989-1993) the widespread availability of acquired immunodeficiency syndrome (AIDS) treatments with antiretroviral and prophylactic interventions, and (2) stage of HIV disease. DESIGN: A prospective cohort study. A group of HIV-1-infected homosexual men were followed from July 1985 through June 1993 and evaluated every 6 months for the presence of clinical symptoms and measurement of the CD4 cell count. To measure the effectiveness of AIDS therapies in this nonrandomized study, we used 2 calendar periods as proxy measures of relative intensity of exposure to antiretroviral therapy. Stage of infection was defined by CD4 cell count and presence of HIV-related clinical symptoms or AIDS. SETTING AND STUDY PARTICIPANTS: Homosexual men infected with HIV-1 from the Multicenter AIDS Cohort Study. MAIN OUTCOME MEASURE: Survival time based on stage of HIV infection. RESULTS: The percentage of HIV-1-infected individuals free of AIDS and clinical symptoms at baseline who survived 2.5 years according to baseline CD4 cell counts of 0 to 0.100, 0.101 to 0.200, and 0.201 to 0.350 x 10(9)/L was 22%, 53%, and 83%, respectively, for the 1985-1988 calendar period, compared with 54%, 71%, and 91%, respectively, for men in the 1989-1993 calendar period. Among men free of AIDS with CD4 cell counts of greater than 0.350 x 10(9)/L, the relative hazard of mortality was 1.6 to 2.3 times higher for those with clinical symptoms compared with those free of clinical symptoms. CONCLUSIONS: Survival of AIDS-free HIV-1-infected individuals with CD4 cell counts of less than 0.350 x 10(9)/L has improved since antiretroviral and HIV prophylactic treatments have become available, but the long-term prognosis remains poor.

Antiviral Agents↗

Endothelin(B) receptor activates NHE-3 by a Ca2+-dependent pathway in OKP cells.

To examine the mechanisms by which endothelin (ET) regulates the Na/H antiporter isoform, NHE-3, OKP cells were stably transfected with ET(A) and ET(B) receptor cDNA. In cells overexpressing ET(B), but not ET(A) receptors, ET-1 increased Na/H antiporter activity (JNa/H). This effect was inhibited by a nonselective endothelin receptor blocker and by a selective ET(B) receptor blocker but was not inhibited by an ET(A) selective receptor blocker. In ET(B)-overexpressing cells, 10(-8) M ET-1 inhibited adenylyl cyclase, but protein kinase A inhibition and pertussis toxin pretreatment did not affect Na/H antiporter activation by ET-1. ET-1 caused a transient increase in cell [Ca2+], followed by a sustained increase. Increases in cell [Ca2+] were partially inhibited by pertussis toxin. ET-1-induced increases in J(Na/H) were 50% inhibited by clamping cell [Ca2+] low with BAPTA, and by KN62, a Ca-calmodulin kinase inhibitor. Inhibitors of protein kinase C, cyclooxygenase, lipoxygenase, and cytochrome P450 and cyclic GMP were without effect. In ET(A)-overexpressing cells, ET-1 increased cell [Ca2+] but did not increase JNa/H. In summary, binding of ET-1 to ET(B) receptors increases Na/H antiporter activity in OKP cells, an effect mediated in part by increases in cell [Ca2+] and Ca-calmodulin kinase. Increases in cell [Ca2+] are not sufficient for Na/H antiporter activation.

Animals↗