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Biomedical subjects

L Zeng

Publications and source records attributed to L Zeng.

At least 127 records · Page 7Linked to original sources
PubMed1998

New bioactive triterpenoids from Melia volkensii.

Bioactivity-directed fractionation of the root bark of Melia volkensii resulted in the isolation of two new natural products, meliavolkinin (1) and melianin C (3), together with two known compounds, 1,3-diacetylvilasinin (2) and melianin B (4). Jones oxidation of 4 gave compounds 3, 23,24-diketomelianin B (5), and 16,23,24-triketomelianin B (6). The structures of the new compounds were elucidated by spectral and chemical data. Compounds 1-6 all showed marginal cytotoxicities against certain human tumor cell lines, while 5 showed selective cytotoxicities for the human prostate (PC-3) and pancreatic (PACA-2) cell lines with potencies comparable to those of adriamycin.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Two new mono-tetrahydrofuran ring acetogenins, annomuricin E and muricapentocin, from the leaves of Annona muricata.

Bioactivity-directed fractionation of the leaf extract of Annona muricata L. (Annonaceae) has resulted in the isolation of two new Annonaceous acetogenins, annomuricine (1) and muricapentocin (2). Compounds 1 and 2 are monotetrahydrofuran ring acetogenins bearing two flanking hydroxyl groups; however, each has three additional hydroxyl groups. Compound 1 has an erythro 1,2-diol, and 2 has a 1,5,9-triol moiety. Both 1 and 2 showed significant cytotoxicities against six types of human tumors, with selectivities to the pancreatic carcinoma (PACA-2) and colon adenocarcinoma (HT-29) cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Retrovirus-mediated DNA repair gene transfer into xeroderma pigmentosum cells: perspectives for a gene therapy.

The rare hereditary disease xeroderma pigmentosum (XP) is clinically characterized by extreme sun sensitivity and an increased predisposition for developing skin cancer. Cultured cells from XP patients exhibit hypersensitivity to ultraviolet (UV) radiation due to the defect in nucleotide excision repair (NER), and other cellular abnormalities. Seven genes identified in the classical XP forms, XPA to XPG, are involved in the NER pathway. In view of developing a strategy of gene therapy for XP, we devised recombinant retrovirus-carrying DNA repair genes for transfer and stable expression of these genes in cells from XP patients. Results showed that these retroviruses are efficient tools for transducing XP fibroblasts and correcting repair-defective cellular phenotypes by recovering normal UV survival, unscheduled DNA synthesis, and RNA synthesis after UV irradiation, and also other cellular abnormalities resulting from NER defects. These results imply that the first step of cellular gene therapy might be accomplished successfully.

Animals↗
PubMed1998

High-resolution detection of five frequencies in a single 3D spectrum: HNHCACO--a bidirectional coherence transfer experiment.

A new triple-resonance pulse sequence, 3D HNHCACO, is introduced and discussed, which identifies sequential correlations of the backbone nuclei (H alpha (i-1), C alpha (i-1), C(i-1), NH(i), N(i)) of doubly labeled proteins in H2O. The three-dimensional (3D) method utilizes a recording of 15N and 13C resonances in a single indirect time domain, the 13C' resonance in another indirect time domain, and detects both NH and H alpha protons. A bidirectional coherence transfer (NH(i) <--> N(i) <--> C(i-1) <--> C alpha (i-1) <--> H alpha (i-1)) is effectuated, resulting in a single high-resolution 3D spectrum that contains the frequencies of all five backbone nuclei. The experiment was applied to the 12.3 kDa ribonuclease from Bacillus intermedius (Binase).

Bacillus↗
PubMed1998

Helium-oxygen improves Clinical Asthma Scores in children with acute bronchiolitis.

OBJECTIVE: To determine the efficacy of a helium-oxygen mixture in children admitted to the pediatric intensive care unit with acute respiratory syncytial virus (RSV) bronchiolitis. DESIGN: Randomized, double-blind, controlled, crossover study and nonrandomized, prospective study. SETTING: A pediatric intensive care unit in a university hospital. PATIENTS: Nonintubated children with signs of acute lower respiratory tract infection and a positive rapid immunoassay for RSV admitted to the pediatric intensive care unit. INTERVENTIONS: Treatment with either helium-oxygen or air-oxygen was administered in random order for 20 mins. Nonrandomized patients received helium-oxygen as initial therapy. MEASUREMENTS AND MAIN RESULTS: Clinical Asthma Score, respiratory rate, heart rate, and pulse oximetry oxygen saturation values were recorded at baseline (before randomization) and at the end of each 20-min treatment period (helium-oxygen or air-oxygen). Nonrandomized patients were studied 20 mins into helium-oxygen delivery. Eighteen patients were studied, 13 of whom were randomized. Five children with severe bronchiolitis (Clinical Asthma Score of > or =6) were initially given helium-oxygen and scored at 20 mins. Mean Clinical Asthma Score was 3.04 (range 1 to 7.5) in the 13 randomized patients and 4.25 (range 1 to 9) in the 18 patients overall. Clinical Asthma Score decreased in the 13 randomized patients (mean 0.46, p < .05) and in the 18 patients overall (mean 1.23, p < .01) during helium-oxygen delivery. In randomized patients with Clinical Asthma Scores of <6 (n = 12), a positive correlation (rs = .72) was observed between the Clinical Asthma Score at baseline and the change in Clinical Asthma Score during helium-oxygen administration (p = .009). Respiratory rate and heart rate decreased during helium-oxygen treatment but were not statistically significant. No complications occurred during helium-oxygen delivery. CONCLUSIONS: Inhaled helium-oxygen improves the overall respiratory status of children with acute RSV lower respiratory tract infection. In patients with mild-to-moderate bronchiolitis (Clinical Asthma Scores of <6), the beneficial effects of helium-oxygen were most pronounced in children with the greatest degree of respiratory compromise.

Acute Disease↗
PubMed1998

Alpha-tubulin missense mutations correlate with antimicrotubule drug resistance in Eleusine indica.

Dinitroaniline herbicides are antimicrotubule drugs that bind to tubulins and inhibit polymerization. As a result of repeated application of dinitroaniline herbicides, highly resistant and intermediately resistant biotypes of goosegrass (Eleusine indica) developed in previously wild-type populations. Three alpha-tubulin cDNA classes (designated TUA1, TUA2, and TUA3) were isolated from each biotype. Nucleotide differences between the susceptible and the resistant (R) alpha-tubulins were identified in TUA1 and TUA2. The most significant differences were missense mutations that occurred in TUA1 of the R and intermediately resistant (I) biotypes. Such mutations convert Thr-239 to Ile in the R biotype and Met-268 to Thr in the I biotype. These amino acid substitutions alter hydrophobicity; therefore, they may alter the dinitroaniline binding property of the protein. These mutations were correlated with the dinitroaniline response phenotypes (Drp). Plants homozygous for susceptibility possessed the wild-type TUA1 allele; plants homozygous for resistance possessed the mutant tua1 allele; and plants heterozygous for susceptibility possessed both wild-type and mutant alleles. Thus, we conclude that TUA1 is at the Drp locus. Using polymerase chain reaction primer-introduced restriction analysis, we demonstrated that goosegrass genomic DNA can be diagnosed for Drp alleles. Although not direct proof, these results suggest that a mutation in an alpha-tubulin gene confers resistance to dinitroanilines in goosegrass.

Alleles↗
PubMed1998

Identification of specific nucleotide sequences within the conserved 3'-SL in the dengue type 2 virus genome required for replication.

The flavivirus genome is a positive-stranded approximately 11-kb RNA including 5' and 3' noncoding regions (NCR) of approximately 100 and 400 to 600 nucleotides (nt), respectively. The 3' NCR contains adjacent, thermodynamically stable, conserved short and long stem-and-loop structures (the 3'-SL), formed by the 3'-terminal approximately 100 nt. The nucleotide sequences within the 3'-SL are not well conserved among species. We examined the requirement for the 3'-SL in the context of dengue virus type 2 (DEN2) replication by mutagenesis of an infectious cDNA copy of a DEN2 genome. Genomic full-length RNA was transcribed in vitro and used to transfect monkey kidney cells. A substitution mutation, in which the 3'-terminal 93 nt constituting the wild-type (wt) DEN2 3'-SL sequence were replaced by the 96-nt sequence of the West Nile virus (WN) 3'-SL, was sublethal for virus replication. An analysis of the growth phenotypes of additional mutant viruses derived from RNAs containing DEN2-WN chimeric 3'-SL structures suggested that the wt DEN2 nucleotide sequence forming the bottom half of the long stem and loop in the 3'-SL was required for viability. One 7-bp substitution mutation in this domain resulted in a mutant virus that grew well in monkey kidney cells but was severely restricted in cultured mosquito cells. In contrast, transpositions of and/or substitutions in the wt DEN2 nucleotide sequence in the top half of the long stem and in the short stem and loop were relatively well tolerated, provided the stem-loop secondary structure was conserved.

Animals↗
PubMed1998

New developments in automated PrepLCMS extends the robustness and utility of the method for compound library analysis and purification.

New developments in the high throughput purification of combinatorial libraries by automated preparative LC-MS is presented. To facilitate high speed purifications at the multimilligram level, short columns operated at ultra high flow rates were incorporated. In order to match the linear velocity of the short analytical columns for high speed separations (operated at 4.0 mL/min), it was required to operate the preparative columns at flow rates in excess of 70 mL/min. For chromatographically well-behaved compounds, analytical LC-MS analyses and preparative LC-MS analyses could be achieved in as little as 5 min. For compounds exhibiting poor chromatographic peak shapes and/or for compound mixtures requiring higher resolution separations, slightly longer preparative LC-MS analysis times were required (8-10 min/sample).

Chemistry, Pharmaceutical↗
PubMed1998

[Alteration and clinical significance of plasma levels of tumor necrosis factor in chronic heart failure].

The plasma levels of tumor necrosis factor (TNF) were measured by enzyme-linked immunoabsorbent assay in 109 patients who were grouped as "non-heart failure" (n = 36), "heart failure" (n = 36) and "cachexia" (n = 37). The results showed that there was no obvious difference in caloric intake among the three groups. Mean plasma levels of TNF were increased in patients with heart failure (0.51 +/- 0.2 ng.ml-1, P < 0.05) and even higher in patients with cachexia (6.19 +/- 2.76 ng.ml-1, P < 0.01) than in patients with non-heart failure (0.085 +/- 0.025 ng.ml-1). In the group with enhanced plasma levels of TNF (TNF > 100 pg.ml-1), the incidence of cachexia (61.0%) was obviously greater than that in the group with normal levels of TNF (17.6%). These findings indicate that plasma levels of TNF are elevated in patients with heart failure; high levels of TNF may play an important role in the pathogenesis of cardiac cachexia.

Adult↗
PubMed1998

[Chemical constituents of Drosera peltata Smith var. lunata (Buch.-Ham.) C.B. clarke collected in Tibet].

OBJECTIVE: To investigate the chemical constituents of the whole plant of Drosera peltata var. lunata collected in Tibet. METHOD: Compounds were separated by means of pH gradient extraction and rechromatography on silica gel, and the structures were determined by spectral analysis and physicochemical evidence. RESULT: Five crystalline compounds were obtained and elucidated as plumbagin(1), droserone(2), hydroxydroserone(3), beta-sitosterol(4) and stigmasterol(5) respectively. CONCLUSION: Compound 3 and 5 were isolated from the plant for the first time.

Drosera↗
PubMed1998

[Thoracoscopic lung reduction surgery for emphysema].

OBJECTIVE: To study the surgical treatment of emphysema. METHOD: Five patients with severe diffused pulmonary emphysema underwent surgical bilateral lung volume reduction by video-assisted thoracoscopy. All patients were male and their age ranged from 60 to 71 years (mean 64.3 years). Before surgery, 5 patients required supplement oxygen with exertion and one oxygen supplement at rest. Preoperative and postoperative assessments included standard pulmonary function studies, chest CT scan and quantitative nuclear lung perfusion and ventilation scan. Wedge resection was performed were in 3 patients, simple plication in 1, and combined wedge resection and plication in 1. There were no early or late mortality and no requirement for immediate postoperative ventilatory assistance. RESULT: Follow-up ranged from 10 to 12 months. After surgery the mean forced expiratory volume in 1 second (FEV(1)) was significantly increased from 0.46 L to 1.13 L (P < 0.001) and the mean forced vital capacity (FVC) was markedly improved from 1.74 L to 2.93 L (P < 0.001). Pulmonary compliance was significantly improved and resistance of airway decreased (P < 0.001). The mean distance during 6-min walk test increased from 10 m to 400 m in 4 patients. CONCLUSION: Thoracoscopic bilateral lung volume reduction is an effective and safe technique for patients with severe emphysema. It can relieve dyspnea and improve in excise tolerance and quality of life.

Aged↗
PubMed1998

[Clinical application of 2 mm micro-thoracoscopic surgery].

OBJECTIVE: To determine the clinical safety and efficacy of micro-thoracoscopic surgery. METHOD: From July 1996 to July 1997, video-assisted thoracoscopic surgery was performed in 47 patients by using 2 mm microthoracoscope. There were 36 males and 11 females. Their age ranged from 40 to 75 years with a mean age of 56.7 years. Surgical procedures included bullectomy (16 patients), wedge resection (3), lung cancer staging (4), lobectomy (2), exploration (15), and resection of mediastinal tumor (2), esophagectomy (1) and repair of pneumothorax (4). Local anesthesia was employed in 18 patients and general anesthesia with double lumen endotracheal tube in 29. RESULT: There were no operative mortality and postoperative complications. CONCLUSION: 2 mm micro-thoracoscopic surgery could be used in the management of a variety of thoracic conditions. It may be of significant value for diagnostic and therapeutic purposes, but the further study for this new technique is required to determine its safety and efficacy.

Adult↗
PubMed1998

EP4/EP2 receptor-specific prostaglandin E2 regulation of interleukin-6 generation by human HSB.2 early T cells.

Human leukemic early T cells of the HSB.2 line coexpress the EP2, EP3 and EP4 subtypes of prostaglandin E2 (PGE2) receptors (Rs). EP3 Rs have previously been demonstrated to transduce PGE2 stimulation of secretion of matrix metalloproteinase (MMP)-9 by HSB.2 T cells through Ca++-dependent enhancement of MMP-9 mRNA transcription. We now show that PGE2 and the EP4/EP2/EP3 R-selective agonist misoprostol, but not the EP3 R-directed agonists sulprostone and M&B28767, induced increases in HSB.2 T cell interleukin-6 (IL-6) mRNA and secretion. Pharmacological agents that increase intracellular concentration of cyclic AMP ([cAMP]i) mimicked and synergistically enhanced induction of IL-6 secretion by PGE2, whereas inhibitors of protein kinase A (PKA) but not protein kinase C suppressed PGE2-evoked increases in IL-6 secretion, suggesting that cAMP and PKA are the intracellular messengers of the PGE2 effect. Exposure of HSB.2 T cells to the mitogenic lectin concanavalin A (Con A) increased basal IL-6 secretion, without a change in IL-6 mRNA level. Con A-stimulated HSB.2 T cells responded to PGE2 with greater increases in IL-6 mRNA and secretion of IL-6. Con A also down-regulated mRNA encoding both EP3 Rs and EP2 Rs, and concurrently up-regulated mRNA encoding EP4 Rs of HSB.2 T cells. Therefore, EP4 and EP2 Rs mediate PGE2-induced increases in IL-6 secretion by HSB.2 T cells through a transcriptional and cAMP dependent-mechanism. The increased ratio of EP4 Rs/EP3 Rs may contribute to Con A enhancement of PGE2-elicited increases in IL-6 secretion by HSB.2 T cells.

Animals↗
PubMed1997

Generation of a high-producing clone of a humanized anti-B-cell lymphoma monoclonal antibody (hLL2).

BACKGROUND: LL2 is a murine immunoglobulin (Ig)G2a-kappa anti-B-cell monoclonal antibody with proven targeting and therapeutic efficacy in the management of non-Hodgkin's lymphoma (NHL). The authors had previously generated a humanized LL2 (hLL2) that demonstrated binding properties identical to those of LL2. Nevertheless, the productivity of the cell line was insufficient for large-scale production of the antibody for clinical studies. Therefore, the authors chose an amplifiable system for the generation of hLL2. METHODS: The hLL2 sequences were ligated into the expression vector pdHL2, which has a dhfr amplifiable gene, and were incorporated into the SP2/0 cells by electroporation. A methotrexate (MTX) resistant clone producing hLL2 was identified. Stepwise increases in MTX concentrations, from 0.1 to 5 microM, and subcloning of the cells by limiting dilution were performed. RESULTS: By amplifying the dhfr and hLL2 genes with stepwise increases in the MTX concentration, the antibody production was enhanced from its original 1.4 to 70 +/- 5 mg per liter of culture media. Subsequent subcloning further improved the productivity. Immunoreactivity of the antibody was conserved, as proven by enzyme-linked immunosorbent assay and cell-binding assays. By isoelectrofocusing, the isoelectric point (pI) of the antibody was measured at approximately 9.6. The productivity of the clone was not affected by culture conditions or storage of the cells in liquid nitrogen. CONCLUSIONS: By means of gene amplification, the authors have generated a high-producing hLL2-IgG clone suitable for production of the quantity of antibody necessary for clinical diagnostic and therapeutic trials of NHL patients.

Antibodies, Monoclonal↗
PubMed1997

The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.

Mutations at the mouse Fused locus have pleiotropic developmental effects, including the formation of axial duplications in homozygous embryos. The product of the Fused locus, Axin, displays similarities to RGS (Regulators of G-Protein Signaling) and Dishevelled proteins. Mutant Fused alleles that cause axial duplications disrupt the major mRNA, suggesting that Axin negatively regulates the response to an axis-inducing signal. Injection of Axin mRNA into Xenopus embryos inhibits dorsal axis formation by interfering with signaling through the Wnt pathway. Furthermore, ventral injection of an Axin mRNA lacking the RGS domain induces an ectopic axis, apparently through a dominant-negative mechanism. Thus, Axin is a novel inhibitor of Wnt signaling and regulates an early step in embryonic axis formation in mammals and amphibians.

Amino Acid Sequence↗
PubMed1997

Beta-globin haplotypes from blood spots for follow-up of newborn hemoglobinopathy screening.

The inheritance of sickle-cell anemia upon the background of the major beta-globin gene cluster haplotypes has been associated with differing risks for major organ failure, and more recently with response to hydroxyurea treatment. Early identification of beta-globin haplotypes in individuals with sickle-cell anemia may be a clinically useful prognostic factor for severity of disease expression. This report describes the use of whole-blood spots on filter papers from newborn hemoglobinopathy screening for beta-globin gene cluster haplotyping by the polymerase chain reaction.

Filtration↗
PubMed1997

Retroviral-mediated correction of DNA repair defect in xeroderma pigmentosum cells is associated with recovery of catalase activity.

Xeroderma pigmentosum (XP) is a rare inherited disease associated with photosensitivity, a very high susceptibility to develop neoplasm on sun-exposed skin and neurological abnormalities for some patients. We previously reported that diploid cell lines established from XP skin biopsies present an abnormal low level of catalase activity, which is involved in the defense against oxygen free radicals. This biochemical dysfunction, probably involved in the skin cancer formation, has been difficult to be directly related to the nucleotide excision repair (NER) defect in XP. In this paper we report that the retroviral-mediated transduction of XP diploid cells by the XPC and XPD/ERCC2 cDNAs fully and stably corrects the NER defect in terms of survival and unscheduled DNA synthesis (UDS) after ultraviolet (UV) irradiation. The catalase activity in transduced cells was recovered up to normal levels only in cells transduced with repair genes correcting the repair defect. These results imply that: (i) the reduced catalase activity in XP, which might result from cellular depletion of its NADPH cofactor, is directly related to impaired DNA repair, and (ii) this depletion might be one of the multiple cellular consequences of XP inborn defect.

Catalase↗