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Biomedical subjects

Z Sheng

Publications and source records attributed to Z Sheng.

At least 19 recordsLinked to original sources
PubMed2001

Chromosomal location of murine disabled-2 gene and structural comparison with its human ortholog.

Disabled-2 (Dab2) is one of the two mammalian orthologs of the Drosophila Disabled. The three spliced forms, p96, p93, and p67 of murine Dab2 cDNAs were first isolated as phosphoproteins functioning in the macrophage CSF-1 signal transduction pathway. Subsequently, the involvement of Dab2 in ovarian cancer development has been investigated: Dab2 expression is lost or greatly diminished in breast and ovarian cancers, and gene deletions have been found. Regulation of Disabled-2 expression is also found to be important in development and physiological functions. Structural information of the murine Dab2 gene is essential for studies of transcription regulation and gene function in mouse models. In this study, the mouse Dab2 gene coding sequence was identified and sequenced from three lambda phage clones containing the gene. Two BAC clones of mouse genomic DNA were also used to identify the sequences of the non-coding first exon and promoter. The first exon is separated from the second exon by a large (15 kb) intron. The mouse gene is about 40 kb in size and consists of 15 exons, producing a 3.6 kb message. The translation initiation site resides in the middle of the second exon. The mouse Dab2 gene structure is very similar to that of its human ortholog in exon/intron sizes and promoter sequences. The chromosomal localization of mouse Dab2 was mapped by FISH to chromosome 15A2, a site of syntax with the human 5p12 where human Dab2 gene resides. The information on the mouse Dab2 gene structure and promoter will be invaluable in studies of the involvement of Dab2 gene in cancer, expression, physiological function, and development in mouse models.

Animals↗
PubMed2000

Angular distributions of fast electrons, ions, and Bremsstrahlung x/gamma-rays in intense laser interaction with solid targets.

We study the angular distributions of fast electrons, ions, and bremsstrahlung x/ gamma-rays generated during the interaction of an ultrashort intense laser pulse with solid targets. A relation is found on the angular directions for fast electrons and ions as a function of the particle's kinetic energy, experienced Coulomb potential changes, and the incident angle of the laser pulse. It is valid independent of the acceleration mechanisms and the polarization of the laser pulse, as confirmed by particle-in-cell simulations. The angular distribution of bremsstrahlung x/gamma-rays is presented to show explicitly its correlation with the corresponding angular distributions of electrons.

Journal Article↗
PubMed2000

Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2).

Disabled-2 (DAB2 for human and Dab2 for other species) is one of two mammalian orthologues of Drosophila Disabled. DAB2 exhibits properties of a tumor suppressor gene: the expression of DAB2 is eliminated in 85-95% of breast and ovarian tumors; homozygous deletions of the gene have been found in some of these tumors; and reintroduction of DAB2 expression suppresses tumorigenicity of carcinoma cells. To study the mechanisms of loss of expression and to detect possible mutations in tumors, we have investigated the genomic structure of the DAB2 gene. The complete DAB2 gene was identified and sequenced from four overlapping BAC clones found to contain the gene. Complement factor 9 (C9) gene was localized next to the DAB2 gene at the 3'-end of the BAC DNA fragments. The human DAB2 gene is about 35 kb in size and consists of 15 exons and 14 introns, producing an approximately 4-kb message. A spliced variant corresponding to mouse Dab2 p93 and a 3'-end spliced variant were also identified. The translation initiation site resides in the second exon, and the noncoding first exon is separated from the second exon by a 14-kb intron. The 420-bp sequence 5' of exon 1 contains a CpG island (39 CpG sites). This 420-bp putative promoter was found to contain the site for transcription initiation, identified by RNase protection assay, and is sufficient for active transcription in epithelial cells. The information about the gene structure of DAB2 will enable us to analyze possible mutations and the mechanisms of loss of DAB2 expression in tumors.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Restoration of positioning control following Disabled-2 expression in ovarian and breast tumor cells.

The physical interaction of epithelial cells with the basement membrane ensures correct positioning and acts as a survival factor for epithelial cells. Cells that detach from the basement membrane often undergo apoptosis; however, in carcinomas, this positional control is absent, permitting disorganized cell proliferation. In the majority of breast and ovarian carcinomas (85-90%), the expression of a candidate tumor suppressor, Disabled-2 (Dab2), is frequently lost. The Dab2-negative tumor cells are no longer in contact with an intact basement membrane, as indicated by the absence of collagen IV (in about 90% of cases). However, in the subset (10-15%) of ovarian tumors in which Dab2 expression is positive, the presence of a basement membrane-like structure around tumor cells was observed. Recombinant adenovirus-mediated expression of Dab2 was used in Dab2-negative ovarian and breast cancer cells, and re-expression of Dab2 was found to lead to cell death or growth arrest. Dab2 expression suppressed MAPK activation and c-fos expression. Plating the infected cells on a basement membrane matrigel rescued the cells from death and growth arrest. Thus, Dab2 exhibits a negative activity for cell growth and survival, which can be countered by attachment of the cells to basement membrane matrix. We conclude that Dab2 functions in cell positioning control and mediates the exigency for basement membrane attachment of epithelial cells. Loss of Dab2 may contribute to the basement membrane-independent, disorganized proliferation of tumor cells in ovarian and breast carcinomas.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Heparin-free hemodialysis in the treatment of hypernatremia in severely burned patients.

BACKGROUND: Hypernatremia in severely burned patients is associated with high morbidity and mortality rates. As the causes of hypernatremia in major burn patients are still not clear, hemodialysis is the method of choice for the treatment. While hemodialysis is effective for the control of hypernatremia, it can cause bleeding complications that may be fatal for burn patients with extensive wounds and potential gastro-intestinal mucosal damage. CLINICAL DATA: In the present study heparin-free hemodialysis in which the heparin is firmly absorbed to the haemofiltration membrane, hemophan, dispensed with systemic use of heparin. In two extensively burned patients with burn area of 100% TBSA and 98% TBSA respectively and hypernatremia with serum sodium concentration as high as 169 and 158 mmol/l respectively, heparin-free hemodialysis was performed five times and three times each. RESULTS: Hypernatremia was satisfactorily corrected with no interference to the coagulation system in the two patients as indicated by clinical observation and biochemical analysis. The patient with burn area of 98% TBSA survived and the patient with burn area of 100% TBSA died of wound coverage failure 6 weeks after injury because of non-availability of autograft. CONCLUSION: Heparin-free hemodialysis is an effective and safe method in the treatment of hypernatremia in extensively burned patients.

Adult↗
PubMed2000

Genomic aberrations in human hepatocellular carcinomas of differing etiologies.

We sought to assess whether genetic abnormalities in hepatocellular carcinoma differed in geographic locations associated with different risk factors. Comparative genomic hybridization (CGH) was applied to the genome-wide chromosomal analysis in 83 tumor samples from four different geographic origins. Samples were obtained from regions that differed in aflatoxin exposure: China (Hong Kong with low aflatoxin exposure and Shanghai with moderate aflatoxin exposure), Japan, and the United States (negligible aflatoxin exposure). Cases from Hong Kong and Shanghai were all hepatitis B virus (HBV) related, those from Japan were hepatitis C virus related, and those from the United States were HBV negative. In parallel, the mutational pattern of the whole p53 gene (exons 1-11) was also investigated in these cases. CGH revealed a complex pattern of chromosomal gains and losses, with the commonest aberration in each geographic location being chromosome 1q copy number gain (38-60%). Shanghai cases displayed the highest number of total aberrations per sample, with significant copy losses on 4q (75%), 8p (70%), and 16q (65%). Hepatitis C virus-related samples from Japan had a characteristically high incidence of 11q13 gain. p53 mutation(s) was detected in 23% of Hong Kong cases, 40% of Shanghai, 31% of Japan, but only 6% of the United States cases. The "aflatoxin-associated" codon 249 mutation was, however, identified only in samples from China (13% Hong Kong and 20% Shanghai). This finding, together with the highly aberrant pattern of genetic changes detected in the Shanghai series, is suggestive of the genotoxic effects of aflatoxin being more broadly based. It is also likely that there is a synergistic effect of HBV infection and high aflatoxin exposure in promoting hepatocellular carcinoma development. It appears from our CGH study that individual risk factors are indeed associated with distinct genetic aberrations, although changes in 1q gain appear common to all.

Adolescent↗
PubMed2000

[A system of microcomputer analysis for biological oxygen consumption and its application].

This paper introduces a microcomputer system of data analysis and methods of measuring oxygen consumption for biological materials. The system overcame some disadvantages of operating inconvenience and difficulties of collective and analytic data by traditional means. The system possesses functions of automatic enactment, collection, save/take and analysis for many experimental data. It can be used to measure oxygen consumption of tissues, cells and mitochondria.

Animals↗
PubMed1999

Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor.

Aminoglycosides are commonly used antimicrobial drugs that often have ototoxic side effects. The ototoxicity often involves permanent loss of cochlear hair cells (HCs). Neurotrophic factors have been shown to protect a variety of tissues, including HCs, from toxic trauma. To determine if glial cell line-derived neurotrophic factor (GDNF) can protect cochlear HCs from trauma, we inoculated an adenoviral vector encoding the human GDNF gene into guinea pig cochleae via the round window membrane 4 days prior to injection of aminoglycosides. Control groups showed little or no negative influence of the viral inoculation on cochlear structure and function. In contrast, ears that were inoculated with the GDNF vector had better hearing and fewer missing HCs after exposure to the ototoxins, as compared with controls. Our results demonstrate the feasibility of gene therapy for cochlear application and suggest that virus-mediated overexpression of GDNF may be developed as a valuable prevention against trauma-induced HC death.

Adenoviridae↗
PubMed1999

Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: relationship to disease stage, tumor size, and cirrhosis.

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prevalent in Southeast Asia. Although the etiological factors associated are now well recognized, the interactions between individual factors and the molecular mechanisms by which they lead to cancer remain unclear. Cytogenetic analysis on HCC has been limited because of poor hepatocyte growth in vitro. The recently developed technique of comparative genomic hybridization (CGH), however, permits screening of the entire genome without the need of cell culture. CGH was applied to the study of genomic aberrations in 67 surgically resected samples of HCC, 3 of adenomatous hyperplasia (AH), and 12 of nontumorous cirrhotic liver surrounding the tumors. All samples were from patients of a racially and etiologically homogeneous population in Southern China, where chronic hepatitis B virus infection is the main etiological factor. CGH analysis of the HCC samples revealed frequent copy number gain of 1q (48/67 cases, 72%), 8q (32/67 cases, 48%), 17q (20/67 cases, 30%), and 20q (25/67 cases, 37%) and common losses on 4q (29/67 cases, 43%), 8p (25/67 cases, 37%), 13q (25/67 cases, 37%), and 16q (20/67 cases, 30%). Our finding of a high incidence of 1q gain strongly suggested this aberration was associated with the development of HCC. Genomic abnormalities were detected in 1 of the 3 AH specimens but absent in all 12 cirrhotic tissues surrounding the tumor. Clinical staging classified 3/67 HCC cases as T1, 53 cases as T2, and 11 cases as T3. No significant difference in the pattern of genomic imbalances was detected between stages T2 and T3. A significant copy number loss of 4q11-q23 was, however, identified in those tumors larger than 3 cm in diameter. Of particular interest was the identification of 8q copy number gain in all 12 cases of HCC that arose in a noncirrhotic liver, compared with only 20/55 cases in HCC arising in a cirrhotic liver. We suggest that 8q over-representation is likely associated with a growth advantage and proliferative stimulation that have encouraged malignant changes in the noncirrhotic human liver.

Adult↗
PubMed1999

Recombinant fusion protein and DNA vaccines against foot and mouth disease virus infection in guinea pig and swine.

In this study, we provide evidence that a recombinant fusion protein containing beta-galactosidase and a tandem repeat peptide of immunogenic dominant epitope of foot-and-mouth disease virus (FMDV) VP1 protein elicits high levels of neutralizing antibody and protects both guinea pigs and swine against infection. Vaccination with this fusion protein induced a FMDV-specific proliferative T-cell response and a neutralizing antibody response. The immunized guinea pigs and swine were protected against FMD type O virus infection. Two DNA plasmids expressing genes of foot-and-mouth disease were constructed. Both plasmids pBO1 and pCO1 contain a signal sequence of the swine immunoglobulin G (IgG) gene and fusion protein gene of pXZ84. The signal sequence and fusion protein gene were under the control of a metallothionein promoter in the case of the pBO1 plasmid and under the control of a cytomegalovirus immediate early promoter in the case of pCO1 plasmid. When pBO1 and pCO1 were inoculated intramuscularly into guinea pigs, both plasmids elicited a neutralizing antibody response and spleen cell proliferation increased following stimulation with FMDV antigen, but animals were not protected from viral challenge.

Animals↗
PubMed1999

Human T-cell lymphotropic virus types I and II infections in mother-child pairs in Nigeria.

A community-based survey to determine the prevalence of human T-cell lymphotropic type I (HTLV-I) and type II (HTLV-II) virus infections in mothers and children in south-western Nigeria was carried out using blood samples collected in 1993. A multistage cluster, random sampling procedure was used to select 460 mother-child pairs (476 children because there were 16 sets of twins) from 14 enumeration areas. A commercially available, whole HTLV-I lysate antigen-based ELISA method was used to screen for HTLV-I and HTLV-II antibodies in the samples. A synthetic peptide antigen-based ELISA was then used to differentiate between antibody reactivity to either HTLV-I or HTLV-II. Reactivity to HTLV-I or HTLV-II antibodies was found in 4.3 per cent (20/460) of mothers and in 1.1 per cent (5/476) of children in both rural and urban communities and all the positive children were males. None of the 16 sets of twins in this study was positive for either HTLV-I or HTLV-II. Also none of the mother-child paired sera tested showed concordance for either HTLV-I or HTLV-II antibody positivity. The lack of concordance between mother and child sera suggests that vertical transmission may not be the major route of transmission of HTLV infection to children in south-western Nigeria. Other modes of transmission, such as the re-use of unsterilized needles for injections and surgical knives in local scarification, which are common practices in the region, need to be investigated as they may prove to be more important than vertical transmission. These findings have important implications for any control programme for diseases that can be spread by the same routes as HTLV infection (the human immunodeficiency viruses, hepatitis B, and hepatitis C infections).

Adult↗
PubMed1999

[Experimental study on the mechanisms of enhancement of aerobic glycolysis of muscles in burns and sepsis--the verification of the existence and the enhancement of the aerobic glycolysis of muscles in early postburn period and sepsis].

OBJECTIVE: To verify if aerobic glycolysis exists in the muscle cells in normal rats and to analyze the changes in aerobic glycolysis in the muscle cells in the early postburn period and in septic states. METHOD: Using septic model of rats, we established the in vitro muscle incubation system with sufficient oxygen supply as well as the NADH fluoremetric method for the detection of trace amount of lactate in the samples. Extensor digitorium longus (EDL) and soleus muscles which represent two types of muscle fiber were studied. RESULTS: In the early postburn period as well as in septic states, the lactate production of muscle cells was significantly elevated as compared to the normal controls even though the muscles were incubated in a fully oxygenated media. The levels of aerobic glyoclysis, as well as its changes in postburn period and in septic states, vary depending on the difference in the fiber composition of the muscles. CONCLUSION: Muscle cells might develop a kind of metabolic enhancement which is referred to as aerobic glycolysis rather than the metabolic defect which results from tissue hypoperfusion and hypoxia in the early postburn period as well as in septic states. This provides us a special insight to elucidate the mechanisms of the metabolic derangement in the early postburn period and in sepsis.

Animals↗
PubMed1998

Randomised placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor for second-degree burns.

BACKGROUND: Wound healing is a dynamic process that could be accelerated by growth factors. We investigated the effect of recombinant bovine basic fibroblast growth factor (rbFGF) on burn healing in a randomised placebo-controlled trial. METHODS: We recruited 600 patients with superficial or deep second-degree burns. Patients received 150 AU/cm2 daily topical rbFGF (n=300) or placebo (n=300) plus vehicle. We assessed healing by photography, punch-biopsy, and clinical examination. FINDINGS: All patients treated with rbFGF had faster granulation tissue formation and epidermal regeneration than those in the placebo group. Superficial and deep second-degree burns treated with rbFGF healed in a mean of 9.9 (SD 2.5) days and 17.0 (4.6) days, respectively, compared with 12.4 (2.7) and 21.2 (4.9) days (p=0.0008 and p=0.0003, respectively). No adverse effects were seen locally or systemically with rbFGF. INTERPRETATION: rbFGF effectively decreased healing time and improved healing quality. Clinical benefits would be shorter hospital stays and the patient's skin quickly becoming available for harvesting and grafting.

Administration, Cutaneous↗
PubMed1998

Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK.

A human fibroblast cDNA expression library was screened for cDNA clones giving rise to flat colonies when transfected into v-Ki-ras-transformed NIH 3T3 cells. One such gene, RECK, encodes a membrane-anchored glycoprotein of about 110 kDa with multiple epidermal growth factor-like repeats and serine-protease inhibitor-like domains. While RECK mRNA is expressed in various human tissues and untransformed cells, it is undetectable in tumor-derived cell lines and oncogenically transformed cells. Restored expression of RECK in malignant cells resulted in suppression of invasive activity with concomitant decrease in the secretion of matrix metalloproteinase-9 (MMP-9), a key enzyme involved in tumor invasion and metastasis. Moreover, purified RECK protein was found to bind to, and inhibit the proteolytic activity of, MMP-9. Thus, RECK may link oncogenic signals to tumor invasion and metastasis.

3T3 Cells↗
PubMed1998

Ischemia and reperfusion impair the gene expression of endogenous basic fibroblast growth factor (bFGF) in rat skeletal muscles.

Our previous studies showed that the amount of endogenous basic fibroblast growth factor (bFGF) was reduced after ischemia and reperfusion insult. One of the mechanisms involved in the decrease of endogenous bFGF is the increased destruction of this growth factor associated with oxygen free radical activation and inflammation. We hypothesized that the wounding also impairs the secretion of bFGF and examined the bFGF gene expression in skeletal muscles after ischemia and reperfusion insult. In this study, a rat leg ischemia (4 h) and reperfusion (24 h) injury model was prepared and the in situ hybridization method and reverse transcriptase polymerase chain reaction technique (RT-PCR) were used to evaluate the bFGF gene expression and its localization in control (normal) and injured rat skeletal muscles. The results showed that the bFGF mRNA expression was localized in the cytoplasm in control skeletal muscle, especially at the periphery inside the cells. According to the intensity of the stain, four main classes of fibers could be identified: strongly, moderately, weakly, and negatively stained fibers. Based on the positive stain, about 82% of the total fibers examined were positive for bFGF mRNA stain. In ischemic or ischemic and reperfused rat skeletal muscles, the localization of bFGF mRNA expression was similar to that in normal skeletal muscles, but only 52% in ischemic muscles and 22% in ischemic and reperfused muscles had positive bFGF mRNA staining. RT-PCR confirmed a significant decrease in bFGF mRNA expression in ischemic and reperfused rat skeletal muscles. These results suggest that the acute ischemia and reperfusion not only induce the destruction of endogenous bFGF molecule, which is stored at the extracellular matrix of the fibers, but also downregulate the bFGF gene expression. The simultaneous dysregulation of endogenous bFGF gene expression and decreased synthesis of bFGF protein suggest a possible role of this growth factor in delayed wound healing.

Animals↗
PubMed1998

Opposing effects of Jun kinase and p38 mitogen-activated protein kinases on cardiomyocyte hypertrophy.

c-Jun N-terminal protein kinase (JNK) and p38, two distinct members of the mitogen-activated protein (MAP) kinase family, regulate gene expression in response to various extracellular stimuli, yet their physiological functions are not completely understood. In this report we show that JNK and p38 exerted opposing effects on the development of myocyte hypertrophy, which is an adaptive physiological process characterized by expression of embryonic genes and unique morphological changes. In rat neonatal ventricular myocytes, both JNK and p38 were stimulated by hypertrophic agonists like endothelin-1, phenylephrine, and leukemia inhibitory factor. Expression of MAP kinase kinase 6b (EE), a constitutive activator of p38, stimulated the expression of atrial natriuretic factor (ANF), which is a genetic marker of in vivo cardiac hypertrophy. Activation of p38 was required for ANF expression induced by the hypertrophic agonists. Furthermore, a specific p38 inhibitor, SB202190, significantly changed hypertrophic morphology induced by the agonists. Surprisingly, activation of JNK led to inhibition of ANF expression induced by MEK kinase 1 (MEKK1) and the hypertrophic agonists. MEKK1-induced ANF expression was also negatively regulated by expression of c-Jun. Our results demonstrate that p38 mediates, but JNK suppresses, the development of myocyte hypertrophy.

Animals↗