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Biomedical subjects

L Zeng

Publications and source records attributed to L Zeng.

At least 55 records · Page 3Linked to original sources

Human herpesvirus 8 envelope glycoprotein K8.1A interaction with the target cells involves heparan sulfate.

Human herpesvirus-8 (HHV-8) or Kaposi's sarcoma-associated herpesvirus K8.1 gene encodes for two immunogenic glycoproteins, gpK8.1A and gpK8.1B, originating from spliced messages. The 228-amino-acid (aa) gpK8.1A is the predominant form associated with the virion envelope, consisting of a 167-aa region identical to gpK8.1B and a 61-aa unique region (L. Zhu, V. Puri, and B. Chandran, Virology 262:237-249, 1999). HHV-8 has a broad in vivo and in vitro cellular tropism, and our studies showed that this may be in part due to HHV-8's interaction with the ubiquitous host cell surface molecule, heparan sulfate (HS). Since HHV-8 K8.1 gene is positionally colinear to the Epstein-Barr virus (EBV) gene encoding the gp350/gp220 protein involved in EBV binding to the target cells, gpK8.1A's ability to interact with the target cells was examined. The gpK8.1A without the transmembrane and carboxyl domains (DeltaTMgpK8.1A) was expressed in a baculovirus system and purified. Radiolabeled purified DeltaTMgpK8.1A protein bound to the target cells, which was blocked by unlabeled DeltaTMgpK8.1A. Unlabeled DeltaTMgpK8.1A blocked the binding of [(3)H]thymidine-labeled purified HHV-8 to the target cells. Binding of radiolabeled DeltaTMgpK8.1A to the target cells was inhibited in a dose-dependent manner by soluble heparin, a glycosaminoglycan (GAG) closely related to HS, but not by other GAGs such as chondroitin sulfate A and C, N-acetyl heparin and de-N-sulfated heparin. Cell surface absorbed DeltaTMgpK8.1A was displaced by soluble heparin. Radiolabeled DeltaTMgpK8.1A also bound to HS expressing Chinese hamster ovary (CHO-K1) cells, and binding to mutant CHO cell lines deficient in HS was significantly reduced. The DeltaTMgpK8.1A specifically bound to heparin-agarose beads, which was inhibited by HS and heparin, but not by other GAGs. Virion envelope-associated gpK8.1A was specifically precipitated by heparin-agarose beads. These findings suggest that gpK8.1A interaction with target cells involves cell surface HS-like moieties, and HHV-8 interaction with HS could be in part mediated by virion envelope-associated gpK8.1A.

Animals↗

Molecular cloning, structure and expression of a novel nuclear RNA-binding cyclophilin-like gene (PPIL4) from human fetal brain.

The cyclophilins are members of a highly conserved, ubiquitous family, and play an important role in protein folding, immunosuppression by cyclosporin A (CsA), and infection of HIV-1 virions. Here we report that a novel member of the cyclophilin family, PPIL4, was cloned and identified during the large-scale sequencing analysis from a human fetal brain cDNA library. The PPIL4 gene encodes a protein which shares 96% amino acid identity with a protein encoded by a putative gene recently cloned from several different early stages of mouse embryo, and its homologues are found in several other organisms. According to bioinformatics analysis, the PPIL4 gene was found to be located in chromosome 6q24-->q25. Besides the PPIase motif, PPIL4 also has an RNA recognition motif (RRM), a pair of bipartite nuclear targeting sequences, and a lysine rich domain. RT-PCR analysis indicated that PPIL4 gene expression is abundant in kidney but has a ubiquitously low expression pattern in other human adult tissues.

Amino Acid Motifs↗

Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Wisconsin Cystic Fibrosis Neonatal Screening Study Group.

OBJECTIVE: Despite its relative frequency among autosomal recessive diseases and the availability of the sweat test, cystic fibrosis (CF) has been difficult to diagnose in early childhood, and delays can lead to severe malnutrition, lung disease, or even death. The Wisconsin CF Neonatal Screening Project was designed as a randomized clinical trial to assess the benefits and risks of early diagnosis through screening. In addition, the incidence of CF was determined, and the validity of our randomization method assessed by comparing 16 demographic variables. METHODOLOGY: Immunoreactive trypsinogen analysis was applied to dried newborn blood specimens for recognition of CF risk from 1985 to 1991 and was coupled to DNA-based detection of the DeltaF508 mutation from 1991 to 1994. Randomization of 650 341 newborns occurred when their blood specimens reached the Wisconsin screening laboratory. This created 2 groups-an early diagnosis, screened cohort and a standard diagnosis or control group. To avoid selection bias, we devised a unique unblinding method with a surveillance program to completely identify the control subjects. Because sequential analysis of nutritional outcome measures revealed significantly better growth in screened patients during 1996, we accelerated the unblinding and completely identified the control group by April 1998. Having each member of this cohort enrolled and evaluated for at least 1 year and having completed a comprehensive surveillance program, we performed another statistical analysis of anthropometric evaluated indices that includes all CF patients without meconium ileus. RESULTS: The incidence of classical CF, ie, patients diagnosed in this trial with a sweat chloride of 60 mEq/L greater, was 1:4189. By incorporating other CF patients born during the randomization period, including 2 autopsy diagnosed patients and 8 probable patients, we calculate a maximum incidence of 1:3938 (95% confidence interval: 3402-4611). Although there were group differences in the proportion of patients with DeltaF508 genotypes and with pancreatic insufficiency, validity of the randomization plan was demonstrated by analyzing 16 demographic variables and finding no significant difference after adjustment for multiple comparisons. Focusing on patients without meconium ileus, we found a marked difference in the mean +/- standard deviation age of diagnosis for screened patients (13 +/- 37 weeks), compared with the standard diagnosis group (100 +/- 117). Anthropometric indices of nutritional status were significantly higher at diagnosis in the screened group, including length/height, weight, and head circumference. During 13 years of study, despite similar nutritional therapy and the inherently better pancreatic status of the control group, analysis of nutritional outcomes revealed significantly greater growth associated with early diagnosis. Most impressively, the screened group had a much lower proportion of patients with weight and height data below the 10th percentile throughout childhood. CONCLUSIONS: Although the screened group had a higher proportion of patients with pancreatic insufficiency, their growth indices were significantly better than those of the control group during the 13-year follow-up evaluation and, therefore, this randomized clinical trial of early CF diagnosis must be interpreted as unequivocally positive. Our conclusions did not change when the height and weight data before 4 years of age for the controls detected by unblinding were included in the analysis. Also, comparison of growth outcomes after 4 years of age in all subjects showed persistence of the significant differences. Therefore, selection bias has been eliminated as a potential explanation. In addition, the results show that severe malnutrition persists after delayed diagnosis of CF and that catch-up may not be possible. We conclude that early diagnosis of CF through neonatal screening combined with aggressive nutritional therapy can result

Cystic Fibrosis↗

Evaluation of germ-cell kinetics in infertile patients with proliferating cell nuclear antigen proliferating index.

AIM: To explore the usefulness of proliferating cell nuclear antigen proliferating index (PCNA PI) in the pathological diagnosis and treatment of male infertility. METHODS: Testicular biopsy specimen obtained from 48 cases of male infertility and 2 normal controls were fixed and embedded. The sections were stained with anti-PCNA monoclonal antibodies or haematoxylin/eosin. Proliferating index (PI), expressed as the percentage of germ-cell nuclei positively stained with PCNA antibody, was assessed from more than 20 seminiferous tubules or 600 germ-cells. RESULTS: The infertile patients were divided into 4 groups: Group 1, normal spermatogenesis (14 cases); Group 2, hypospermatogenesis (16 cases); Group 3, germinal arrest (10 cases); Group 4, Sertoli cell only syndrome (8 cases). The PCNA PI of normal control testis was 86.5% (mean value). Group 3 had a significantly lower PCNA PI (29.8%) than normal testis; Group 1 and 2 had similar PIs (82.3% and 82.3%, respectively) as the control testis. PI of the negative control (Group 4) was 0 as no germ-cells were found. CONCLUSION: PCNA PI is useful for assessing germ-cell kinetics, especially for pathological diagnosis of germinal arrest which is difficult to differentiate by routine HE staining technique. In germinal arrest, there is a significantly lowered PCNA PI, which is an indication of DNA synthesis deterioration, suggesting the use of therapies be different from those for hypospermatogenesis.

Adult↗

[Controlling effect of parasitoids on population of vegetable leaf miner Liriomyza sativae Blanchard].

The controlling effect of parasitoids on vegetable leaf miner, Liriomyza sativae Blanchard, was evaluated by using acting factor life tables and exclusion inex of population control(EPIC). The results showed that Chrysocharis pentheus, Neuchrysocharis formosa, Chrysonotomyia okazakii, Hemiptarsenus varicornis, Chrysocharis sp., Opius dimidiatus and Opius dissitus played an important role in controlling the population of vegetable leaf miner. The EIPCs of parasitoids were 1.23, 2.73, 5.98, 5.92 and 5.71, respectively for the five generations of L. sativae on kidney bean planted in spring, from the 1st to the 5th generation and, for the 2nd generation in particular, they were 2.73, 2.87, 2.24 and 1.89, respectively on kidney bean, cowpea, luffa and cucumber, indicating that if the parasitoids were excluded, the population of the next generation of L. sativae would increase by times accordingly. The EIPC of parasitoids for the 3rd instar larvae was usually the largest among different instar larvae and pupae, and the EIPCs for the 3rd to 5th generation of L. sativae on spring kidney bean were higher than those for the 1st and the 2nd. The EIPCs of parasitoids for L. sativae on kidney bean and cowpea were larger than those on luffa and cucumber.

Animals↗

[Carcinoma of kidney collecting duct: an analysis of 10 cases].

OBJECTIVE: To study the clinicopathologic characteristics of renal collecting duct carcinoma (CDC). METHODS: A retrospective study was done in 10 cases of CDC. RESULTS: Among 466 cases of renal cell carcinoma admitted in our Institute between January 1989 and June 30, 1999, 10(2.1%) cases of CDC were identified. Seven presented with gross hematuria and 3 with abdominal pain. Radical nephrectomy was done in 9 patients, enucleation of tumor in one. The primary tumor was located predominantly in the renal medulla. Histologic examination showed prominent tubular or tubulopapillary structures. Sarcomatoid carcinoma, cystadenocarcinoma, nests and cords of tumor cells in desmoplastic stroma were identified in some cases. High molecular weight cytokeratin 34 beta E12 was positive in 8 cases and peanut agglutinin in 7 cases. According to Fuhrman's nuclear grade, one was in G2, 4 were in G3 and 5 in G4. Six patients died of metastases within 3 to 23 months (mean 13.3 months), one died of heart disease with tumor free after 19 months, two survived with tumor free for 14 months and 39 months, respectively, one lost from follow-up. CONCLUSION: CDC is a distinctive renal cell carcinoma with prominent clinical appearance and progressive clinical course.

Adult↗

[A study of hepatitis B virus(HBV) anti-genome and its inhibitory effect on HBV replication].

OBJECTIVE: To study the combination of triplex forming oligodeoxynucleotides (TFO) with hepatitis B virus gene and its effect on replication of HBV. METHODS: An oligodeoxynucleotide (TFO20) which can form triplex with SP1 sites in HBV core promoter was synthesized and was linked with biotin. Both the liposome-TFO20 and naked TFO20 were transfected to HepG2.2.15 cells, which was detected by SABC assay and showed signals that TFO20 was combined with HBV DNA. ELISA, reverse transcript (RT)-PCR and fluorescence quantitative PCR were used to investigate the change of HBV DNA, 3.5 kb/3.4 kb RNA, 2.4 kb/2.1 kb RNA, HBsAg and HBeAg in HepG2.2.15 cells before and after treatment with TFO20. RESULTS: The ratio of liposome-TFO20 and naked TFO20 transfected to HepG2.2.15 cells were 80% and 40%, respectively. TFO20 signals mainly distributed in the nucleus and cytoplasm. After treatment with TFO20, the level of HBV DNA was reduced from 10(7.01) to 10(4.94), while 3.5 kb/3.4 kb RNA, 2.4 kb/2.1 kb RNA, HBsAg and HBeAg were also reduced by 70.2%, 31.6%, 37.0%, 78.2% respectively. CONCLUSIONS: TFO20 can be transfected into cells by packing with liposome and can be combined with HBV DNA. TFO20 can effectively inhibit replication of HBV.

DNA Viruses↗

[Development of biogenic VOC emissions inventory with high temporal and spatial resolution].

A new method was developed to estimate biogenic VOC emissions with high temporal and spatial resolution by use of Mesoscale Meteorology Modeling System Version5 (MM5). In this method, the isoprene and monoterpene standard emission factors for some types of tree in China were given and the standard VOC emission factors and seasonally average densities of leaf biomass for all types of vegetation were determined. A biogenic VOC emissions inventory in South China was established which could meet the requirement of regional air quality modeling. Total biogenic VOC emissions in a typical summer day were estimated to be 1.12 x 10(4) metric tons in an area of 729 km x 729 km of South China. The results showed the temporal and spatial distributions of biogenic VOC emission rates in this area. The results also showed that the geographical distribution of biogenic VOC emission rates depended on vegetation types and their distributions and the diurnal variation mainly depended on the solar radiation and temperature. The uncertainties of estimating biogenic VOC emissions were also discussed.

Atmosphere↗

[The relationship of clinicopathology and immunophenotypes in non-Hodgkin's lymphomas of the spleen].

OBJECTIVE: To investigate the relationship between clinicopathologic features and immunophenotypes in non-Hodgkin's lymphoma (NHL) of the spleen. METHODS: Clinicopathologic analysis and follow up; immunohistologic staining by SP method and EBER in situ hybridization. RESULTS: (1) Splenomegaly was found in all 19 cases of spleen NHL, 10 of the 19 (52.6%) cases had masses or a mass in their enlarged spleen; (2) 14 of the 19 (73.7%) cases were of B-cell type (including 5 cases of follicular type and 9 cases of diffuse type), in which 8 cases were centroblastic, 3 of centroblast/centrocyte and 4 cases of small lymphocyte types; all 10 cases of primary splenic lymphomas (PSL) were B-cell type; (3) 5 of the 19 cases (26.3%) had peripheral T-cell origin, including 4 cases of large cell type and 1 case of small cell type; of the 3 TIA-1 positive cases, 2 were also positive for EBER 1/2 (one CD 8+ and another CD56+), the remaining case was CD8-, CD56-, EBER1/2-; all 5 cases were secondary NHL of the spleen; (4) Follow up data were obtained for 14/19 cases (73.7%). 8 of 9 surviving cases were primary NHL. The range of survival period varied from 8 to 10 years. All 5 deceased cases had secondary NHL and their survival period was 2 to 6 months. CONCLUSIONS: Some relationship exists between the clinicopathology and origin of the tumor cells in splenic NHL, the prognosis of primary NHL is better than that of the secondary NHL and the diagnosis of primary NHL should be made with discretion.

Adolescent↗

Induction of cyclin-dependent kinase 5 in the hippocampus by chronic electroconvulsive seizures: role of [Delta]FosB.

The transcription factor DeltaFosB is induced in the hippocampus and other brain regions by repeated electroconvulsive seizures (ECS), an effective antidepressant treatment. The unusually high stability of this protein makes it an attractive candidate to mediate some of the long-lasting changes in the brain caused by ECS treatment. To understand how DeltaFosB might alter brain function, we examined the gene expression profiles in the hippocampus of inducible transgenic mice that express DeltaFosB in this brain region by the use of cDNA expression arrays that contain 588 genes. Of the 430 genes detected, 20 genes were consistently upregulated, and 14 genes were downregulated, by >50%. One of the upregulated genes is cyclin-dependent kinase 5 (cdk5). On the basis of its purported role in regulating neuronal structure, we studied directly whether cdk5 is a true target for DeltaFosB. Upregulation of cdk5 immunoreactivity in the hippocampus was confirmed by Western blotting in the DeltaFosB-expressing transgenic mice as well as in rats treated chronically with ECS. Chronic ECS treatment also increased, in the hippocampus, the phosphorylation state of tau, a microtubule-associated protein that is a known substrate for cdk5. A 1.6 kb fragment of the cdk5 promoter was cloned, and activity of the promoter was found to be increased after overexpression of DeltaFosB in cell culture. Moreover, mutation of the single consensus activator protein-1 site contained within the cdk5 promoter fragment completely abolished activation of the promoter by DeltaFosB. Together, these results suggest that cdk5 is one target by which DeltaFosB produces some of its physiological effects in the hippocampus and thereby mediates certain long-term consequences of chronic ECS treatment.

Animals↗

The rat liver Na(+)/bile acid cotransporter. Importance of the cytoplasmic tail to function and plasma membrane targeting.

To understand the potential functions of the cytoplasmic tail of Na(+)/taurocholate cotransporter (Ntcp) and to determine the basolateral sorting mechanisms for this transporter, green fluorescent protein-fused wild type and mutant rat Ntcps were constructed and the transport properties and cellular localization were assessed in transfected COS 7 and Madin-Darby canine kidney (MDCK) cells. Truncation of the 56-amino acid cytoplasmic tail demonstrates that the cytoplasmic tail of rat Ntcp is involved membrane delivery of this protein in nonpolarized and polarized cells and removal of the tail does not affect the bile acid transport function of Ntcp. Using site-directed mutagenesis, two tyrosine residues, Tyr-321 and Tyr-307, in the cytoplasmic tail of Ntcp have been identified as important for the basolateral sorting of rat Ntcp in transfected MDCK cells. Tyr-321 appears to be the major basolateral-sorting determinant, and Tyr-307 acts as a supporting determinant to ensure delivery of the transporter to the basolateral surface, especially at high levels of protein expression. When the two Tyr-based basolateral sorting motifs have been removed, the N-linked carbohydrate groups direct the tyrosine to alanine mutants to the apical surface of transfected MDCK cells. The major basolateral sorting determinant Tyr-321 is within a novel beta-turn unfavorable tetrapeptide Y(321)KAA, which has not been found in any naturally occurring basolateral sorting motifs. Two-dimensional NMR spectroscopy of a 24-mer peptide corresponding to the sequence from Tyr-307 to Thr-330 on the cytoplasmic tail of Ntcp confirms that both the Tyr-321 and Tyr-307 regions do not adopt any turn structure. Since the major motif YKAA contains a beta-turn unfavorable structure, the Ntcp basolateral sorting may not be related to the clathrin-adaptor complex pathway, as is the case for many basolateral proteins.

Amino Acid Sequence↗

Wisconsin cystic fibrosis chest radiograph scoring system: validation and standardization for application to longitudinal studies.

This study was designed to achieve a final modeling, validation, and standardization plan for the Wisconsin cystic fibrosis (CF) chest radiographic scoring system. Sixty chest radiographs were selected to reflect a range of severity of lung pathology in children with CF. Seven experienced volunteer raters (three radiologists and four pediatric pulmonologists) from five institutions were recruited to evaluate and score the films. Analysis of scores revealed that the subcomponents of the Wisconsin system showed considerable variation from rater to rater, but reliability assessment indicated satisfactory Cronbach's alpha coefficients (0.83-0.90) among the seven raters. It was found that an additive method of total score computation is significantly more reliable (P < 0.05) than either the original multiplicative model or the traditional Brasfield scoring system. Comparison of radiologists and pulmonologists revealed a marked, systematic difference in scoring with the former group being more conservative in interpretation of abnormalities than the pulmonologists, and some of the raters showing very limited sensitivity. Quantitative chest radiology applied to children with cystic fibrosis studied long-term in longitudinal research projects requires the careful use of sensitive scoring methods and careful selection and training of multiple raters. This is particularly important since pulmonologists and radiologists can differ systematically in interpreting/scoring abnormalities.

Child↗

Suppression of streptococcal cell wall-induced arthritis by human chorionic gonadotropin.

OBJECTIVE: To determine whether human chorionic gonadotropin (HCG) contributes to pregnancy-associated immunosuppression, as observed clinically by an amelioration of symptoms in human autoimmune diseases, including rheumatoid arthritis, during pregnancy. METHODS: Administration of HCG was initiated 2 days prior to an arthritogenic dose of streptococcal cell wall (SCW) in nonpregnant female rats, and the development and severity of SCW-induced arthritis was monitored. Inflammatory mediators, including plasma nitrite/nitrate and cytokine levels, were measured. Inducible nitric oxide synthase (iNOS) protein and cytokine messenger RNA expression in joint tissue were compared between treated and untreated arthritic animals. RESULTS: Systemic administration of HCG resulted in a dose-dependent reduction in the clinical arthritis index. Consistent with the amelioration of clinical symptoms, HCG significantly reduced the inflammatory cell infiltration, pannus formation, and bone and cartilage degradation. Mechanistically, HCG therapy was associated with suppression of the overzealous production of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-1beta, which contribute to synovial pathology in animals with SCW-induced arthritis. Circulating nitric oxide and the amount of iNOS protein were also reduced. Furthermore, circulating transforming growth factor beta levels were elevated by the HCG, all of which suggest monocytes/macrophages as a potential target. CONCLUSION: These findings indicate that HCG exerts a protective effect in this experimental arthritis model, through modulation of inflammatory mediators.

Animals↗

Study on the correlation of plasma NO, ET-1 and ALT in the patients with chronic hepatitis and cirrhosis.

The levels of plasma nitric oxide (NO), endothelin-1 (ET-1) and ALT in the patients with chronic hepatitis B and active cirrhosis and the correlation among them were observed and analyzed. NO3- was restored by using cadmium column assay and NO2- measured by heavy nitrogen assay. The primitive NO3- and total restored NO2- (NO3-/NO2-) in plasma of the patients with chronic hepatitis and cirrhosis. Plasma ET-1 and ALT levels were determined by using radioimmunological assay and Lai's assay, respectively. Compared with normal control group, the plasma levels of NO2-/NO2- and ET-1 in the patients with chronic active hepatitis and active cirrhosis were significantly increased (P < 0.05-0.01). There was a positive correlation between NO and ALT, and ET-1 and ALT in the patients with chronic active hepatitis and active cirrhosis respectively. It was suggested that elevation of both NO and ET-1 levels were closely related with injury severity of liver function.

Adolescent↗

Observation of T lymphocyte subsets in the liver of patients with advanced schistosomiasis and advanced schistosomiasis accompanied with hepatitis B.

T lymphocyte subsets in the liver were detected by Avidin-Biotin Complex (ABC) assay in 22 patients with advanced schistosomiasis (AS) and 5 cases of AS accompanied with hepatitis B. T lymphocytes in the liver of AS patients were distributed in the peripheral layer of egg granuloma or the area near eggs in non-granuloma. No infiltrative T lymphocytes were observed in area with extensive fibrosis. There was infiltration of many T cells in the portal tract, piecemeal and focal necrosis area as well as in hepatic sinus in AS patients accompanied with hepatitis B. CD8+ T cells (suppressor/cytotoxic T cells, Ts/Tc) in the liver were predominant in the two groups. In AS patients, marked hepatic fibrosis, a small number of T cell infiltration and slight hepatocellular degeneration and necrosis were observed. However, obvious hepatocellular degeneration and necrosis were seen in AS patients accompanied with hepatitis B, and 3 cases of them developed active liver cirrhosis. The results indicated immune response was weak in the liver in AS patients and Ts cells might be predominant in the subset of CD8+ T lymphocytes. Cellular immune response was relatively strong in AS patients accompanied with hepatitis B and the infiltrative CD8+ T lymphocytes might be mainly Tc cells.

Adolescent↗