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Biomedical subjects

L Zhu

Publications and source records attributed to L Zhu.

At least 217 records · Page 12Linked to original sources

A "defeated" rice resistance gene acts as a QTL against a virulent strain of Xanthomonas oryzae pv. oryzae.

The genetic components responsible for qualitative and quantitative resistance of rice plants to three strains (CR4, CXO8, and CR6) of Xanthomonas oryzae pv. oryzae (Xoo) were investigated using a set of 315 recombinant inbred lines (RILs) from the cross Lemont (japonica) x Teqing (indica) and a complete linkage map with 182 well distributed RFLP markers. We mapped a major gene (Xa4) and ten quantitative trait loci (QTLs) which were largely responsible for segregation of the resistance phenotype in the RILs. The Teqing allele at the Xa4 locus, Xa4T, acted as a dominant resistance gene against CR4 and CXO8. The breakdown of Xa4T-associated resistance mediated by the mutant allele at the avrXa4 locus in the virulent strain CR6 results from significant changes in both gene action (lose of dominance) and the magnitude of gene effect (approximately 50% reduction). Nevertheless, Xa4T still acted as a recessive QTL with a significant residual effect against CR6. The mutant alleles at the avrXa4 locus in CXO8 and CR6 that lead to a reduction in effect, or "breakdown", of Xa4T were apparently accompanied by corresponding penalties for their fitness. The quantitative component of resistance to Xoo in the RILs was largely due to a number of resistance QTLs. Most resistance QTLs mapped to genomic locations where major resistance genes and/or QTLs for resistance to Xoo, blast and sheath blight were identified in the same cross. Most QTLs showed consistent levels of resistance against all three Xoo strains. Our results suggest that a high level of durable resistance to Xoo may be achieved by the cumulative effects of multiple QTLs, including the residual effects of "defeated" major resistance genes.

Chromosome Mapping↗

Role of mitogen-activated protein kinases in activation-induced apoptosis of T cells.

A member of the mitogen-activated protein (MAP) kinase family, Jun N-terminal kinase (JNK), has been implicated in regulating apoptosis in various cell types. We have investigated the requirement for another type of MAP kinase, extracellular signal-regulated protein kinase (ERK) in activation-induced cell death (AICD) of T cells. AICD is the process by which recently activated T cells undergo apoptosis when restimulated through the T-cell antigen receptor. Here we show that both JNK and ERK are activated rapidly upon T-cell receptor (TCR) ligation prior to the onset of AICD. A chemical inhibitor of ERK activation, PD 098059, inhibits ERK activation and apoptosis, while JNK activation is not inhibited. This suggests that JNK activation is not sufficient for apoptosis. TCR cross-linking induces expression of the apoptosis-inducing factor, Fas ligand (FasL), and its expression correlates with ERK activation. In addition, apoptosis induced by direct ligation of the Fas receptor by anti-Fas antibody is not associated with ERK activation and is not inhibited by PD 098059. These data suggest that ERK activation is an early event during T-cell apoptosis induced by antigen-receptor ligation, and is not involved in apoptosis per se but in the expression of FasL. MAP kinase family members may be similarly involved in inducing apoptosis signals in other cell types.

Animals↗

Systemic mycobacterial infection inhibits antigen-specific immunoglobulin E production, bronchial mucus production and eosinophilic inflammation induced by allergen.

As the burden of infectious diseases becomes reduced in many countries, a remarkable increase in the incidence of allergies has occurred. The basis for the rise in atopic disorders as a correlate of the decline in infectious diseases has not been defined. In the present study, we tested experimentally whether prior systemic infection with Mycobacterium bovis bacillus Calmette Guérin (BCG) had any effect on ovalbumin (OVA) Al(OH)3 (alum)-induced immunoglobulin E (IgE) production, airway mucus production and eosinophilic inflammation. The data showed that allergen-specific IgE production and OVA-induced eosinophilia and goblet cell development were significantly inhibited by prior infection with BCG. Correspondingly, following immunization with OVA alum, BCG-infected mice exhibited significantly higher levels of allergen-driven interferon-gamma (IFN-gamma) production than the mice without infection. The ratio of IFN-gamma: interleukin (IL)-4 production was higher in OVA-sensitized mice with prior BCG infection than in those without infection. The abrogation of OVA-induced mucus production and pulmonary eosinophilia in BCG-infected mice correlated with significantly decreased IL-5 production and increased IFN-gamma and IL-12 production. These data provide direct evidence that intracellular bacterial infection (i.e. BCG) can inhibit antigen-specific IgE and airway reactivity induced by environmental allergen. Furthermore, the results suggest that changes in cytokine-producing patterns of T lymphocytes and other cells may be the mechanism by which infections influence allergies.

Allergens↗

Vascular complications of diabetes mellitus.

1. Macro- and microvascular diseases are the main chronic complications of diabetes mellitus (DM). 2. It has been shown that DM patients have more severe nailfold microcirculatory disturbances than patients with liver cirrhosis or systemic lupus erythematosus (SLE). 3. It has been shown that the glomerular basement membrane of diabetic rats is significantly thickened compared with that of normal rats (295.5 +/- 45.1 vs 184.8 +/- 33.2 nm). 4. Gastric mucosal blood flow (GMBF) in 41 patients with non-insulin-dependent diabetes mellitus (NIDDM) was determined with a laser Doppler flowmeter. The results showed that average GMBF values at 14 sites in the gastric mucosa were significantly lower in NIDDM patients than in control subjects. 5. The percentage of painless acute myocardial infarction (AMI) among 50 patients with DM was 22.0% and the mortality of AMI was 22.0% (11 cases). Both these values were higher than the corresponding values in patients without DM (9.9 and 11.4%, respectively; P < 0.05). 6. Cerebrovascular disease is more prevalent in diabetic patients than in non-diabetics and the mortality of stroke in DM patients is two-fold higher than that of non-diabetic patients. 7. Diabetes can result in widespread macrovascular atherosclerosis and microcirculatory disorders of multiple organs.

Animals↗

Immunogenicity and protective efficacy of DNA vaccines encoding secreted and non-secreted forms of Mycobacterium tuberculosis Ag85A.

OBJECTIVE: To determine the efficacy of Ag85A-DNA against challenge with a highly virulent human clinical isolate of Mycobacterium tuberculosis (CSU37) and to compare the potencies of two types of Ag85A-DNA vaccines; those expressing secreted and non-secreted forms of the protein. DESIGN: Ag85A-DNA vaccinated mice were challenged with a highly virulent clinical isolate of M. tuberculosis (CSU37) in order to compare the efficacy of these vaccines. In vitro studies were also performed. RESULTS: Enhanced humoral and cellular responses were induced in mice vaccinated with the secreted Ag85A-DNA compared to the non-secreted Ag85A-DNA. In addition, secreted Ag85A-DNA conferred protective immunity against infection with M. tuberculosis (CSU37). CONCLUSIONS: DNA vaccines encoding M. tuberculosis Ag85A have been shown to induce potent humoral and cellular immune responses leading to protection from M. tuberculosis (Erdman) challenge in mouse models. In this study we demonstrate that Ag85A can confer protection in a rigorous challenge model using a highly virulent human clinical isolate of M. tuberculosis (CSU37). This challenge model appears able to discriminate between DNA vaccines of differing potencies, as the more immunogenic DNA construct encoding a secreted form of Ag85A was protective, whereas the less immunogenic DNA construct encoding a non-secreted form of Ag85A was not.

Acyltransferases↗

Plasma apolipoprotein B-48, hepatic apolipoprotein B mRNA editing and apolipoprotein B mRNA editing catalytic subunit-1 mRNA levels are altered in zinc-deficient rats.

Apolipoprotein B (apoB) exists as two major isoforms and serves as an obligatory component of lipid-rich plasma lipoprotein particles. Apolipoprotein B mRNA editing is a zinc-dependent, site-specific cytidine deamination that determines whether the apoB-100 or apoB-48 isoform is synthesized. The objective of this work was to examine whether dietary zinc levels affect apoB mRNA editing in vivo. Adult male Sprague-Dawley rats were randomly assigned to zinc-deficient (ZD, <0.5 mg Zn/kg diet), zinc-adequate (ZA, 30 mg Zn/kg diet) or zinc-replenished (ZDA, ZD rats fed the ZA diet for last 2 d) dietary groups for 18 d. The ratio of plasma apolipoprotein B-48 (apoB-48) to total apoB was significantly lower in zinc-deficient compared with zinc-adequate rats. Primer extension analysis indicated a modest but significant reduction in hepatic apoB mRNA editing in ZD rats compared with that of the ZA group. In ZDA rats, hepatic apoB mRNA editing and the percentage of plasma apoB-48 to total apoB were not different from ZA rats. The mRNA abundance of hepatic apobec-1 (apoB mRNA editing catalytic subunit 1) was significantly lower in ZD and ZDA rats than in ZA rats. In summary, the plasma ratio of apoB-48 to total apoB protein as well as hepatic apoB mRNA editing and hepatic apobec-1 mRNA levels were reduced in rats consuming a zinc-deficient diet. These data suggest that one or more components of apoB metabolism may be influenced by dietary zinc status.

Animals↗

Domain mapping of the human cytomegalovirus IE1-72 and cellular p107 protein-protein interaction and the possible functional consequences.

Our previous work demonstrated that following human cytomegalovirus (HCMV) infection of fibroblasts, there was a protein-protein interaction between the HCMV IE1-72 immediate-early (IE) protein and the cellular p107 protein which resulted in the alleviation of p107-mediated transcriptional repression of E2F-responsive promoters. In a further characterization of this interaction, we now show that IE1-72 binds to the N-terminal portion of p107, not the C-terminal 'pocket' region that binds E2F-4, and where a number of other viral gene products bind. Additionally, we show that exons 2 and 3 of IE1-72 are required for binding to p107. After mapping the binding domains, we next wanted to address the additional functional consequences of this interaction. It is well known that p107 can negatively regulate cell growth. To examine whether IE1-72 can also overcome this growth suppression, we transfected and infected or cotransfected various constructs into SAOS-2 cells. We showed that infection of SAOS-2 cells was capable of alleviating p107-mediated growth suppression. Additionally, we showed that IE1-72 alone is capable of overcoming p107-mediated growth arrest. Alleviation of this repression by IE1-72 is dependent on the protein-protein interaction between p107 and IE1-72 as deletion mutants of either protein which lack the identified binding domains fail to achieve this effect. These data indicate that the IE1-72 protein is capable of overcoming p107-mediated blocks in cellular proliferation, events that occur in both productive and non-productive HCMV infections.

Blotting, Western↗

Evaluation of the effectiveness of transurethral radio frequency hyperthermia in the canine prostate: temperature distribution analysis.

The heating pattern of a transurethral radio frequency (RF) applicator and its induced steady-state temperature field in the prostate during transurethral hyperthermia treatment were investigated in this study. The specific absorption rate (SAR) of the electromagnetic energy was first quantified in a tissue-equivalent gel phantom. It was used in conjunction with the Pennes bioheat transfer equation to model the steady-state temperature field in prostate during the treatment. Theoretical predictions were compared to in vivo temperature measurements in the canine prostate and good agreement was found to validate the model. The prostatic tissue temperature rise and its relation to the effect of blood perfusion were analyzed. Blood perfusion is found to be an important factor for removal of heat especially at the higher RF heating level. To achieve a temperature above 44 degrees C within 10 percent of the prostatic tissue volume, the minimum RF power required ranges from 5.5 W to 36.4 W depending on the local blood perfusion rate (omega = 0.2-1.5 ml/gm/min). The corresponding histological results from the treatment suggest that to obtain better treatment results, either higher RF power level or longer treatment time (> 180 minutes) is necessary. This is consistent with the predictions from the theoretical model developed in this study.

Animals↗

Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8.

Human herpesvirus 8 (HHV8) infects Kaposi's sarcoma (KS) spindle cells in situ, as well as the lesional endothelial cells considered to be spindle cell precursors. The HHV8 genome contains several oncogenes, suggesting that infection of endothelial and spindle cells could induce cellular transformation and tumorigenesis and promote the formation of KS lesions. To investigate the potential of HHV8 infection of endothelial cells to contribute to the development of KS, we have developed an in vitro model utilizing dermal microvascular endothelial cells that support significant HHV8 infection. In contrast to existing in vitro systems used to study HHV8 pathogenesis, the majority of dermal endothelial cells are infected with HHV8 and the viral genome is maintained indefinitely. Infection is predominantly latent, with a small percentage of cells supporting lytic replication, and latency is responsive to lytic induction stimuli. Infected endothelial cells develop a spindle shape resembling that of KS lesional cells and show characteristics of a transformed phenotype, including loss of contact inhibition and acquisition of anchorage-independent growth. These results describe a relevant model system in which to study virus-host interactions in vitro and demonstrate the ability of HHV8 to induce phenotypic changes in infected endothelial cells that resemble characteristics of KS spindle cells in vivo. Thus, our results are consistent with a direct role for HHV8 in the pathogenesis of KS.

Agar↗

9-cis retinoic acid induces monocyte chemoattractant protein-1 secretion in human monocytic THP-1 cells.

Monocyte migration and activation are regulated by monocyte chemoattractant protein-1 (MCP-1). Prior studies have shown MCP-1 expression is modulated by a variety of ligands that act through extracellular receptors. In the current study, we show 9-cis retinoic acid (RA), a ligand for the nuclear hormone receptor retinoid X receptor (RXR) and retinoic acid receptor (RAR), markedly induces the expression of MCP-1. In human THP-1 monocytic leukemia cells cultured with RA (0.05 to 500 nmol/L), MCP-1 expression was induced rapidly, significantly, and dose-dependently by as much as 165-fold. MCP-1 RNA level was also increased in RA-treated cells. Expression of PPARgamma, a heterodimer partner of RXR, is also markedly induced by RA in THP-1 cells. However, BRL49653, a PPARgamma ligand, failed to induce MCP-1 secretion either alone or to modify the expression level induced by RA. In contrast, BRL49653 significantly increased MCP-1 (biotinylated MCP-1) binding to THP-1 cells, whereas RA had no effect. Other peroxisome proliferator activated receptor (PPAR) ligands, 15d-PGJ(2) and troglitazone (PPARgamma), Wy14,643 (PPARalpha), and PD195599 (PPARbeta) inhibited the induction of MCP-1 by RA. RA's effect on MCP-1 expression in human elutriated monocytes were similar to that observed in the THP-1 cells. These studies identify RA as a nuclear signal for MCP-1 induction in undifferentiated human monocytic cells. These studies also suggest monocyte MCP-1 expression induced through RA may modulate cell migration.

Alitretinoin↗

Examining associations between childhood asthma and traffic flow using a geographic information system.

Using geographic information systems (GIS) and routinely collected data, we explored whether childhood residence near busy roads was associated with asthma in a low-income population in San Diego County, California. We examined the locations of residences of 5,996 children [less than/equal to] 14 years of age who were diagnosed with asthma in 1993 and compared them to a random control series of nonrespiratory diagnoses (n = 2,284). Locations of the children's residences were linked to traffic count data at streets within 550 ft. We also examined the number of medical care visits in 1993 for children with asthma to determine if the number of visits was related to traffic flow. Analysis of the distribution of cases and controls by quintiles and by the 90th, 95th, and 99th percentiles of traffic flow at the highest traffic street, nearest street, and total of all streets within a 550-ft buffer region did not show any significantly elevated odds ratios. However, among cases, those residing near high traffic flows (measured at the nearest street) were more likely than those residing near lower traffic flows to have two or more medical care visits for asthma than to have only one visit for asthma during the year. The results of this exploratory study suggest that higher traffic flows may be related to an increase in repeated medical visits for asthmatic children. Repeated exposure to particulate matter and other air pollutants from traffic exhaust may aggravate asthmatic symptoms in individuals already diagnosed with asthma.

Adolescent↗

Mitral valve replacement with complete mitral leaflet retention: operative techniques.

BACKGROUND AND AIMS OF THE STUDY: This report describes surgical indication and operative technique of complete preservation of the mitral valvular and subvalvular apparatus during mitral valve replacement. METHODS: Twenty patients, 12 with rheumatic lesions and eight with congenital lesions, were operated between 1991 and 1996. The left atrium was opened using a trans-septal approach through the right atrium in 17 patients, and at the intra-atrial groove in three. The valve was sized without excising any mitral valvular or subvalvular tissue. Teflon pledget-reinforced horizontal mattress valve sutures were passed from the left atrium, through the mitral annulus, around the free edge of mitral leaflet, and up through the prosthetic sewing ring. The prosthetic valve was seated and the sutures tied, reefing the native leaflets and compressing them between the sewing ring and native annulus. Thus, chordal tension on the ventricle was evenly maintained. RESULTS: There was no operative or late death. Postoperative results were excellent. Echocardiography showed that none of the patients had any observable anterior leaflet and redundant subvalvular tissue in the left ventricular outflow tract (LVOT); thus, neither LVOT obstruction nor interference with prosthetic valve function occurred. CONCLUSIONS: Based on these findings, it is suggested that when mitral valve replacement is required in patients with mitral insufficiency (MI) or MI with mild stenosis, the mitral valvular and subvalvular tissue should be completely preserved.

Adult↗

[Relationships of angiotensinogen gene M235T variant with diabetic nephropathy in Chinese type 2 diabetes mellitus].

OBJECTIVE: To investigate whether angiotensinogen(AGT) gene M235T variant is associated with type 2 diabetes mellitus without nephropathy (DM) and/or diabetic nephropathy (DN) in Chinese type 2 diabetes. METHODS: AGT genotypes of 84 cases with DM, 96 with DN and 98 controls were determined by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism analysis of the region of the variant. RESULTS: Increased frequencies of T allele (0.82) and TT genotype (0.70) were observed in 96 subjects with DN, compared with those observed in 98 control subjects (0.63 and 0. 43 respectively, P = 0.003, P = 0.0004). The odds ratio associated with TT genotype was 3.47 (95% CI 1.51-7.94, P = 0.0033) for DN in analysis adjusted for several DN risk factors. There was no difference in allele distribution between 84 DM patients and the controls. CONCLUSION: TT genotype of the AGT gene might be an independent risk factor of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.

Adult↗

[Pregnancy of patients conceived within one year after chemotherapy for gestational trophoblastic tumor].

OBJECTIVE: To explore the risk of pregnancy in patients conceived within one year after successful chemotherapy for gestational trophoblastic tumor. METHODS: 22 patients conceived within one year after chemotherapy were followed up and analysed about abnormal pregnant result, wastage rate and the time of interval between chemotherapy and pregnancy. RESULTS: Among 22 cases, 9 cases were full term birth, 6 cases were wastage. The wastage rate was 27.3%. The wastage rate of these patients conceived within half a year was higher than one year (P < 0.05). 1 repeated hydatidiform mole and one post term choriocarcinoma occurred in 22 patients. They both were conceived within 5 months after chemotherapy. CONCLUSIONS: Preservation of fertility is feasible in patients suffering from choriocarcimona and invasive mole. But these patients should practise contraception at least half a year after chemotherapy, and it's better to advise patients to take contraception for one year.

Adult↗

Resistant mechanisms of Candida albicans to fluconazole.

OBJECTIVE: To detect the resistant mechanisms of Candida albicans to fluconazole (FCZ) at molecular biology level, since the resistance mechanisms of azole antifungal agents have been the focus of attention these years. METHODS: Thirty-two FCZ-resistant C. albicans were selected as our test strains (MICs > or = 64 micrograms/ml). With 14-alpha-demethylase gene (ERG16 gene, target enzyme encoding gene of azoles) as our object, we chose six sets of primers from the ERG16 gene to amplify the interested fragments, and conducted Southern blot hybridization, restriction fragment length polymorphism (RFLP), and single strand conformation polymorphism (SSCP) analysis for the fragments which were amplified by the six sets of primers, and pre-resistant sensitive strains were used as controls. Three representative fragments, A66, D66 and E78, were selected to be cloned and sequenced. RESULTS: The polymerase chain reaction (PCR) amplification showed that several tested strains were negative for some primers. However, our Southern blot analysis reminded that their resistance did not result from the lack of target enzyme coding gene. SSCP analysis showed that differences were noted between the resistant and sensitive strains and inter-resistant strains. Statistical analysis showed that the most variable sequence lied in the amplifier of the sixth pair of primer, and all the tested 32 strains showed positive results. In the 11 mutation points we found, five resulted in amino acid alterations. It is likely that one or more mutational alterations (alone or in combination) might lead to the expression of an enzyme highly resistant to the inhibitory action of FCZ which in turn is responsible for the FCZ resistant trait in these strains. CONCLUSION: One or more mutational alterations might lead to the azole resistant trait in this strains.

Acquired Immunodeficiency Syndrome↗

The change of insulin-like growth factor-1 in diabetic patients with neuropathy.

OBJECTIVE: To evaluate the possible relationship between insulin-like growth factor-1 (IGF-1) and diabetic neuropathy (DNP). METHODS: Sixty-nine patients with Type 2 non-insulin-dependent diabetes (54 with peripheral neuropathy and 15 without neuropathy) were observed. Normal controls were 34 non-diabetic persons. Diabetic peripheral neuropathy diagnosis was carried out taking into account results of NS, ND, NC and AF. After an overnight fast, blood was taken for IGF-1, glucose, hemoglobin Alc, C-peptide, and insulin. Plasma IGF-1 was measured by radioimmunoassay (RIA) method. RESULTS: The neuropathic group had significantly lower levels for IGF-1 (86.43 ng/ml +/- 45.18 ng/ml) compared to normal controls (119.68 ng/ml +/- 89.42 ng/ml) (P < 0.05), and to diabetic patients without neuropathy (113.75 ng/ml +/- 66.58 ng/ml) (P < 0.05). No significant difference was found between diabetic non-neuropathic group and normal control subjects (P < 0.05). In diabetic subjects there was a positive correlation (gamma = 0.27, P < 0.05) between IGF-1 and beat to variation in heart rate. There were negative correlation between IGF-1 and postprandial blood glucose (gamma = -0.3, P < 0.05), and aspartic acid translocase (gamma = -0.27, P < 0.05). CONCLUSION: In diabetic patients with peripheral neuropathy there are abnormalities of IGF-1 that may contribute to the pathogeneses of diabetic neuropathy.

Aged↗

[The experimental study on improved cuirass-respirator].

OBJECTIVE: To study the factors that possibly affect the ventilatory efficiency of cuirass-respirator. METHODS: Cuirass shells were constructed with plaster casts according to the shape of dog's chest wall. Above the cuirass shell, two straps were added in order to hold the cuirass shell when the pump generated pressure. Tidal volume and Pab and Pes were measured during different negative pressure. In addition, tidal volume was recorded before and after the cuirass was held. RESULTS: Ventilatory efficiency was markedly raised after the cuirass was held. As negative pressure rose, ventilation increased and Pdi decreased. CONCLUSIONS: The improved cuirass respirator can markedly improve ventilatory efficiency.

Air Pressure↗