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Biomedical subjects

H Zheng

Publications and source records attributed to H Zheng.

At least 361 records · Page 20Linked to original sources
PubMed1994

[Nasal NK-cell lymphoma].

A 75-year-old man was admitted to our hospital on June 1st, 1993, because of nasal obstruction, epistaxis, fever, night sweats and weight loss. Examination disclosed a 2-cm white necrotic mass in the nasal septum, and a biopsy disclosed non-Hodgkin's lymphoma, diffuse, mixed-type. Imprint smears showed cytoplasmic azurophilic granules in the tumor cells. Dense granules were demonstrated by electron microscopy. The tumor cells were CD1-2+3-4-7+8-16+56+57-, and T cell receptor genes were in germline configuration. NK activity against K562 was strongly positive. Based on morphologic, phenotypic, immunogenotypic, and cytotoxic findings, the tumor cells seemed to be derived from activated NK cells. Because the tumor cells were positive for the EB virus and CD21 antigen, EB virus seemed to have infected CD21-positive NK cells and transformed them. MDR P-glycoprotein was also positive. This finding may explain why nasal lymphomas are resistant to chemotherapy and have a poor prognosis.

Cell Transformation, Viral↗
PubMed1993

Hoxb-4 (Hox-2.6) mutant mice show homeotic transformation of a cervical vertebra and defects in the closure of the sternal rudiments.

Two Hoxb-4 (Hox-2.6) mutations were introduced into the mouse germline. The overt phenotype caused by one of the mutations was assayed on two different genetic backgrounds, an inbred 129SvEv and a hybrid 129SvEv-C57BL/6J. The allele hoxb-4' is a disruption of the first exon and causes two obvious skeletal changes: a partial homeotic transformation of the second cervical vertebra from axis to atlas and a defective morphogenesis of the sternum. Both phenotypes have incomplete penetrance and variable expressivity when assayed in the hybrid genetic background, but the sternum defect is completely penetrant in the inbred background. The mutant allele hoxb-4s has a premature stop codon, introduced by the "hit and run" method in the second exon, that disrupts the third helix of the homeodomain. This allele also causes the partial homeotic transformation of axis to atlas, but it does not affect the sternum.

Animals↗
PubMed1993

Role of protein phosphorylation in TNF-induced apoptosis: phosphatase inhibitors synergize with TNF to activate DNA fragmentation in normal as well as TNF-resistant U937 variants.

This study examined the role of protein phosphorylation in TNF induction of apoptosis in several tumor cell lines by testing the effects of agents that either stimulate or inhibit protein phosphorylation. The serine-threonine phosphatase inhibitors, okadaic acid (OKA) and calyculin A (CLA), synergistically augmented TNF-induced apoptosis in several TNF-sensitive tumor cell lines including the U937 histiocytic lymphoma, the BT-20 mammary carcinoma, and the LNCap prostatic tumor cell line. Furthermore, the phosphatase inhibitors completely reversed the TNF resistance of a variant (U9-TR) derived from U937. CLA also inhibited phosphatase activity in cell-free extracts from both U937 and U9-TR at the same concentrations (0.4-2.0 nM) that it synergized with TNF. In contrast, TNF treatment of U937 cells did not result in inhibition of phosphatase activity mediated by protein phosphatase 1 (PP1) and PP2A in cell extracts. Since the phosphatase inhibitors are known to increase the overall levels of protein phosphorylation in cells, this suggested that TNF may act by stimulating protein kinase (PK) activity. This hypothesis was supported by the results of testing a panel of relatively specific protein kinase inhibitors. TNF activation of DNA fragmentation was blocked by a potent inhibitor of myosin light chain kinase (MLCK) but was unaffected by inhibitors of cAMP or cGMP-dependent PKs. We postulate that a defect in the activation of MLCK or possibly some other as yet unknown PK may be responsible for the TNF resistance of U9-TR. Furthermore, this resistance may be circumvented by promoting protein phosphorylation with the serine-threonine-dependent phosphatase inhibitors.

Alkaloids↗
PubMed1993

Regulation of neutrophil interleukin 8 gene expression and protein secretion by LPS, TNF-alpha, and IL-1 beta.

Neutrophils are possibly involved in the pathogenesis of various lung diseases through the release of numerous mediators. In the present study, we studied the regulation of IL-8 gene induction and protein secretion in human blood neutrophils. Northern blot analysis revealed that LPS increased IL-8 mRNA levels in neutrophils, with a maximal fivefold increase by 2 h. IL-8 mRNa levels returned to baseline values within 12 h. In contrast, LPS-stimulated monocytes demonstrated a sustained increase of IL-8 mRNA levels for more than 24 h. TNF-alpha, IL-1 beta, and phorbol myristate acetate also increased IL-8 mRNA levels in neutrophils. Immunohistochemical analysis confirmed that IL-8 was localized within stimulated neutrophils. IL-8 secretion by neutrophils and monocytes was quantified using a specific ELISA for IL-8. Resting neutrophils secreted minimal IL-8 activity. However when cells were stimulated with LPS, TNF-alpha, or IL-1B, neutrophils secreted IL-8. IL-8 secretion was most marked during the first 2 h after stimulation and decreased thereafter. In contrast, monocytes maintained a high rate of IL-8 secretion over 12 h. Although a single monocyte secreted 70-fold more IL-8 than did a single neutrophil after 4 h of incubation, the high abundance of neutrophils in peripheral blood made the neutrophil-secreted IL-8 more significant. During the first 2 h, neutrophils secreted approximately 40% of the IL-8 released by monocytes in the same volume of blood. This ratio decreased to 9% after 12 h. Neutrophil-secreted IL-8 may play an autocrine or paracrine role during the initial stage of inflammation.

Cells, Cultured↗
PubMed1993

Antimicrobial activity of rabbit CAP18-derived peptides.

A cationic antimicrobial protein of 18 kDa (CAP18) was originally isolated from rabbit granulocytes by using as an assay the agglutination of Re-lipopolysaccharide-coated erythrocytes. The C-terminal 37 amino acids of CAP18 (CAP18(106-142)) make up the lipopolysaccharide-binding domain. Synthetic CAP18(106-142) has broad antimicrobial activity against both gram-positive (50% inhibitory concentration, 130 to 200 nM) and gram-negative (50% inhibitory concentration, 20 to 100 nM) bacteria. Susceptible strains include Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium. Antimicrobial activity is highly dependent on peptide structure. Although a 32-amino-acid peptide resulting from the truncation of 5 amino acids from the C terminus of CAP18(106-142) is highly active, other fragments of CAP18(106-142), including CAP18(106-142) with a truncated N terminus, do not exhibit antimicrobial activity. Unlike previously characterized antimicrobial peptides derived from granulocyte proteins, CAP18(106-142) is active in serum. CAP18(106-142) or a derivative peptide may have therapeutic potential for bacterial sepsis.

Agglutination Tests↗
PubMed1993

[Studies on the establishment of malarial animal model of short-term relapse. IV. Short-term relapse in rhesus monkeys infected with sporozoites of Plasmodium cynomolgi].

The present paper reports that the short-term relapse could be artificially made by the application of the experimental method, and thus we established the monkey model of the short-term relapse. According to the experimental design, when the parasitemia was detected in rhesus monkeys infected with sporozoites of Plasmodium cynomolgi, a combined therapy of pyronaridine 6 mg/kg body weight, artemether 10 mg/kg and chloroquine 20 mg/kg once daily for 3 days was carried out to clear the erythrocytic parasite and then the short-term relapse was observed in the animal follow-up for 100 days. The combined therapy was given again when relapse occurred. One onset of relapse occurred on 47 days after therapy in monkey M194 infected with sporozoites 11 x 10(3). In M195 infected with sporozoites 55 x 10(4), relapses occurred for 3 times on 30, 37 and 51 days respectively after medication, but during a follow-up period of 200 days, no relapse was shown in M192 and M193 infected with sporozoites 50 and 55 x 10(2), respectively. The results showed that the frequency of the short-term relapse was relative to the sporozoites inoculation, and sporozoites less than 11 x 10(3) were not suitable for making short-term relapse in animal model. No long term relapse could be seen in all the 4 monkeys until 400 days. Under existing conditions that the relapse was generally explained with hypnozoite assumption, the establishment of animal model of short-term relapse could be tenable.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Preparation of monoclonal antibody against basic glutathione S-transferase and its clinical application].

Balb/c mice were immunized with basic glutathione s-transferase (B-GST) prepared from human liver and the monoclonal antibody against B-GST was purified. Serum B-GST level was measured in 234 patients with various types of viral hepatitis with solid radioimmuno-sandwich assay and the value in 70 donors (4.19 +/- 4.42 ng/ml) used as control. The serum B-GST level in 117 cases with acute icteric hepatitis, 85 cases with chronic active hepatitis and 32 cases with severe hepatitis were 8.6, 8.4 and 5.9 times higher than that of the controls respectively. At the same time, serum alanine amino-transferase (ALT) activity in patients with various types of viral hepatitis were 6.8, 3.1 and 2.4 times higher respectively. These results showed that the change of serum B-GST level was more prominent than that of ALT activity. In addition, the change of B-GST in 35 patients with CAH and 13 with severe hepatitis were serially observed. Serum B-GST level persisted at high level for a long time in most of the patients, while serum ALT activity soon became normal. It is shown that serum B-GST level is more valuable than ALT in estimating chronic and severe liver damage.

Adult↗
PubMed1993

[Studies on the establishment of malarial animal model of short-term relapse. III. Combined therapy with pyronaridine-artemether-chloroquine for parasitemia clearance].

To establish a Plasmodium cynomolgi-monkey model of short-term relapse, different antimalarials have been used to inhibit recrudescence so as to elude the confusion between the two different onsets. When a single dose of effective schizonticides pyronaridine, artemether or chloroquine was administered, recrudesence readily occurred. This paper reports the results of the combined therapy with the above three drugs. Seven rhesus monkeys from Guangxi Autonomous Region infected with Plasmodium cynomolgi from Vietnam by blood transmission were rapidly cured by combined therapy with pyronaridine 6 mg/kg-artemether 100 mg/kg-chloroquine 10 mg/kg (PAC-1) once daily for 3 days. The average time of parasite clearance was 3.43 +/- 0.89 d and the curvilinear regression equation of parasite density after treatment was Y = 10(3.94-0.83X). Severe side effects of the gastrointestinal tract occurred during the course of treatment, though no recrudescence was found after 300-400 days. To reduce the side effects, another test was carried out in 3 monkeys and the dosage regimen was modified to pyronaridine 6 mg/kg-artemether 10 mg/kg-chloroquine 20 mg/kg (PAC-2) once daily for 3 days. There was no obvious side effect in the tested monkeys and the parasites were cleared during a mean time of 2.67 +/- 0.58 d and the curvilinear regression equation of parasite density was Y = 10(3.7-1.46X). No recrudescence was detected in the animals during a follow-up of 180 days. The study shows that PAC-2 regimen of the combined therapy is effective for parasitemia clearance and might be adopted for establishment of the monkey model of short-term relapse.

Animals↗
PubMed1993

[Synthetic oligopeptide of hepatitis D virus antigen and its clinical application].

A 27-peptide fragment derived from natural HDAg sequence was selected, identified and synthesized. It was used to develop an EIA method for detection of anti-HD. The 27-peptide possessed the similar antigenicity with the corresponding fragment of natural HDAg, and could also compete with natural HDAg for serum anti-HD. High specificity and no cross-reaction were found among the peptide and normal human sera, normal mice sera and sera positive with HAV, HBV or HCV antibody alone. 36 serum samples were identified previously, with Abbott kits with a coincident rate of 97.2%. Anti-HD was also detected in serum samples of some blood donors and patients with liver diseases and HBV infection from 1990-1992. One (0.33%) of 300 blood donors was positive (two times higher than normal ALT level in serum). 62 patients with hepatitis A and 58 patients with non-hepatitis B were anti-HD negative. 100 (11.64%) of 859 patients with HBV infection were positive: ASC 13/410 (3.17%), AH 7/63 (10.29%), CPH 1/9 (11.11%), CAH 22/121 (18.18%), SH 15/75 (20.00%), LC 23/78 (29.49%), PHC 19/89 (19.39%). The results are consistent with our previous reports.

Animals↗
PubMed1993

[Clinical study on patients with lateral position test (LPT) for determining the relative function on each lung].

Comparing the lateral position test (LPT) on 20 patients of lung cancer with bronchospirometry of tracheal intubation, the authors found that the VC, oxygen uptake were in high positive correlation, while VE were in moderate positive correlation. Therefore, they conclude that LPT could substitute the complicated tracheal intubation for determining the relative function of each lung before the total pneumonectomy.

Carcinoma, Bronchogenic↗
PubMed1993

[Analysis of estrogen receptors in normal bone and bone tumor tissues].

Thirteen human normal bone and fifteen bone tumor tissues were assayed for estrogen receptor (ER) by Dextran-coated Charcoal method (Scatchard plot). The results showed that the concentrations of ER in normal bone tissues (15.12 +/- 14.68 fmol/mg pro) were higher than that of bone malignant tumors (8.04 +/- 6.71 fmol/mg pro) P < 0.05). The binding dissociation constants (Kd) of ER in bone tumors (18.46 +/- 27.10 x 10(-11) mol/L) was lower than those in normal ones (39.91 +/- 20.13 x 10(-11) mol/L) (P < 0.025). The percentages for positive score of ER in normal and tumor ones (23.1%, 26.7%) were not significantly different (P > 0.05). Our study indicated that the variations of concentration and affinity of ER in bone related to the tumor incidence. That cytosol ER content was decreased in malignant bone tumors whereas that of affinity increase suggests an impairment or change of an intact receptor mechanism in this tissues.

Adolescent↗
PubMed1993

Nicotine inhibition of apoptosis suggests a role in tumor promotion.

Recent evidence indicates that cell death through apoptosis may be an important mechanism to prevent tumor development. Therefore, agents that inhibit apoptosis may function as tumor promoters. The purpose of this study was to determine the effects of nicotine on the process of apoptosis. The results demonstrate that nicotine inhibits apoptosis induced by diverse stimuli including tumor necrosis factor (TNF), UV light, chemotherapeutic drugs, and calcium ionophore. This phenomenon was observed in normal and transformed cells derived from a variety of species and tissues, including tumor cell types related to tobacco use. The major nicotine metabolite, cotinine, also inhibited apoptosis, whereas N-nitrosodiethylamine, a carcinogen found in tobacco, was without effect. Therefore, nicotine-mediated inhibition of apoptosis may contribute to the pathogenesis of tobacco-related cancer as well as decrease the efficacy of cancer therapies.

Animals↗
PubMed1992

Antisense oligodeoxynucleotides as probes of T-lymphocyte gene function.

Conventional and thiophosphonate-derivatized oligonucleotides were employed to specifically regulate functional gene expression in murine T-cell hybridomas. For example, induction of apoptotic cell death following activation of T-cell hybridomas was examined using antisense oligonucleotides corresponding to several protooncogenes. We found that antisense oligodeoxynucleotides corresponding to c-myc inhibited both the characteristic DNA fragmentation and the loss of cell viability following activation without affecting production of lymphokines. Functional antisense oligonucleotides corresponding to c-fos had no effect in this system. These results demonstrate the use of antisense oligonucleotides to regulate function in T-cell hybridomas and provide valuable insights into the molecular bases of this biological phenomenon. Antisense oligonucleotides were also used to study another problem, the relation of T-cell-derived antigen-specific immunoregulatory factors to the T-cell receptor (TCR). Because the translation start of each TCR gene usually varies from one T cell to another, antisense oligonucleotides corresponding to the TCR V alpha or V beta of different cells were shown to act in a cell-specific manner. Furthermore, this method was used to demonstrate that a soluble antigen-specific regulatory activity produced by one of the T-cell lines depends on expression of the specific TCRa, an observation that has since been confirmed by gene transfer experiments. Expression of the CD3-TCR complex on the cell surface was also blocked by antisense oligonucleotides corresponding to CD3 gamma and CD3 zeta; however, neither these nor TCR V beta antisense oligonucleotides had any effect on production of the soluble regulatory activity.

Animals↗
PubMed1992

Genetic manipulation of the mouse via gene targeting in embryonic stem cells.

Gene targeting applied to totipotent embryonic stem (ES) cells is a very powerful means of creating highly specific mutations of genes in the mouse. The successful application of this technology is however constrained by both the types of mutations that can be generated at a target locus and the ability to reconstruct a germline chimera from the manipulated cells. We have developed two cell lines that can be routinely transmitted through the germline of chimeras after cloning and prolonged selection in tissue culture. We have also established a variety of methods for generating non-selected mutations at the X-linked hprt locus in ES cells. Our observations at this locus have enabled us to generate successfully a subtle mutation at the non-selectable Hox-2.6 locus.

Animals↗