Biomedical subjects

Yan Zhang

Publications and source records attributed to Yan Zhang.

At least 361 records · Page 20Linked to original sources

PubMed2004

[The study for the immuno-protection of E. coli O157:H7 outer membrane protein].

OBJECTIVE: To evaluate the protective efficacy against a lethal dose of E. coli O157:H7 after intranasal, oral and subcutaneous immunization with the outer membrane protein (OMP) extracted from the whole cell of E. coli O157:H7. METHODS: Female BALB/C mice were immunized three times (on days 0, 7 and 14) with OMP and CT or Complete Frund adjuvant. On the 21st day after the last immunization, serum, fecal extracts and vaginal washes were collected for the detection of antigen-specific antibody responses by ELISA before the oral challenge with E. coli O157:H7 933. And the antigens that induced the specific antibody responses were analysed by Western-blotting. Then, the mice were orally challenged with 0.3 ml 4.25 x 10(10)/ml live E. coli O157:H7, and the mortality was recorded. On the 7th day after the challenge, the mice were sacrificed and the heart, liver, lung, kidney, small intestine and colon were collected. Then the histology lesions were observed by light microscopy. RESULTS: In ELISA, both intranasal and oral immunization, with CT as a mucosal adjuvant, induced strong anti-OMP IgA responses in serum, fecal extract and vaginal washes, and anti-OMP IgG responses in serum. However, the intranasal immunization was much more effective to induce specific IgA and IgG responses than the oral immunization. In contrast to mucosal immunization, subcutaneous immunization only induced high levels of specific IgG antibodies in serum, and did not effectively promote IgA immune response. The results of the protective efficacy after challenge showed that both intranasal and oral immunizations with OMP provided significant protection (86.7% to 40%, P < 0.01 and 73.3% to 40%, P < 0.05) against a lethal dose of E. coli O157:H7 challenge, and intranasal immunization possessed a better protective ability (86.7% to 73.3%, P < 0.05). In contrast, the mice immunized subcutaneously were not protected. They were died more early after oral challenge. Furthermore, the histopathological features of the kidney, colon and other organs also appeared to be well correlated with immunization route. In comparison with the mice immunized subcutaneously and those in control group, the severity of the histopathological lesions in the tissues of the mice immunized intranasally was minimal. CONCLUSION: These results suggested that the intranasal immunization should be the best choice of vaccine development against E. coli O157:H7.

Administration, Intranasal↗

PubMed2004

Essential requirement for both hsf1 and hsf2 transcriptional activity in spermatogenesis and male fertility.

Heat shock factors (Hsfs) are major transactivators of heat shock proteins but are also involved in regulation of other genes active in embryonic development. High expression levels of Hsfs in mouse testis during development suggest a role for these factors in spermatogenesis, a cyclic process of spermatogonia cell-differentiation into mature spermatozoa. In contrast to hsf1(-/-) mice, which exhibit normal spermatogenesis, targeted disruption of hsf2 results in reduced testicular size but only a small impairment in male fertility. We show here that disruption of both hsf1 and hsf2 results in a more severe phenotype associated with male sterility due to severe defects in spermatogenesis. Earliest defects observed are the reduced number of germ cells in juvenile mice and germ cells that enter the meiotic prophase fail to progress beyond the pachytene stage. This was associated with a reduction or absence of transcription of genes critically involved in spermatogenesis. The findings suggest that additive or synergistic transcriptional activity of both hsf1 and hsf2 is required for normal mammalian spermatogenesis and male fertility.

Animals↗

PubMed2004

Unique contribution of heat shock transcription factor 4 in ocular lens development and fiber cell differentiation.

Mammalian ocular lens development results via a differentiation program that is highly regulated by tissue-specific transcription factors. Central to this is the terminal differentiation of fiber cells, which develop from epithelial cells on the anterior surface of the lens, accompanied by a change in cell shape and expression of structural proteins (such as membrane proteins MP19, MIP26, connexin 43, 46, and 50, cytoskeletal proteins CP49, CP115, and alpha, beta, and gamma crystallins), creating a transparent, refractive index gradient in the lens. Mutations in genes controlling eye development and in lens structural protein genes are associated with multiple ocular developmental disorders, including cataracts and other opacities of the lens. Here we show that heat shock transcription factor 4 (HSF4) expression in the developing lens is required for correct lens development and that inactivation of hsf4 leads to early postnatal cataract formation with primary effects specific to terminal fiber cell differentiation. These data suggest that HSF4 acts as a critical transcription factor for lens-specific target gene expression, in particular regulating the small 25 kDa heat shock protein that acts as a modifier for lens opacity and cataract development. Thus, HSF4 fulfills a central role in controlling spatial and temporal expression of genes critical for correct development and function of the lens.

Animals↗

PubMed2004

Reference-scan-free method for automated correction of Nyquist ghost artifacts in echoplanar brain images.

One of the most common artifacts for echo-planar imaging is the Nyquist ghost, typically overcome with the aid of a reference scan preceding the actual image acquisition. In this work, a nonlinear phase correction obviating the need for a reference scan is proposed. The method is based on computing the second moments of the even and odd subdomains of the phase-encoding k-space data to retrieve the phase disparities between even and odd echoes. The method's underlying assumption is that the images are dominated by their low frequency and symmetric part. In vivo data demonstrate the effectiveness of the algorithm showing ghost suppression comparable to that achievable with the reference-scan method.

Algorithms↗

PubMed2004

Determination of thymus and activation-regulated chemokine (TARC)-contents in scales of atopic dermatitis.

BACKGROUND: Thymus and activation-regulated chemokine (TARC) is a cytokine which selectively controls the migration of type 2-helper T lymphocytes into inflammatory lesions, and the serum level is strongly associated with disease severity of atopic dermatitis (AD). OBJECTIVE: To examine the role of TARC in the pathogenesis of AD, we determined TARC-contents in the scales obtained from lesional skin of the patients with AD. RESULTS: High amount of TARC was detected in the scales of lesional skin obtained from the patients with AD, and the amount was well correlated with the serum IgE levels but not with the blood eosinophil counts. The TARC-content in the lesional scales was not correlated with a-431C/T polymorphism of TARC promotor gene, suggesting other regulating mechanisms in TARC production in the lesion. CONCLUSION: High amount of TARC is produced in the kesion of AD, and analysis of cytokine content in lesional scales may provide some tools to clarify the pathogenesis of AD.

Chemokine CCL17↗

PubMed2004

Crystal structure of an aminoimidazole riboside kinase from Salmonella enterica: implications for the evolution of the ribokinase superfamily.

The crystal structures of a Salmonella enterica aminoimidazole riboside (AIRs) kinase, its complex with the substrate AIRs, and its complex with AIRs and an ATP analog were determined at 2.6 angstroms, 2.9 angstroms, and 2.7 angstroms, respectively. The product of the Salmonella-specific gene stm4066, AIRs kinase, is a homodimer with one active site per monomer. The core structure, consisting of an eight-stranded beta sheet flanked by eight alpha helices, indicates that AIRs kinase is a member of the ribokinase superfamily. Unlike ribokinase and adenosine kinase in this superfamily, AIRs kinase does not show significant conformational changes upon substrate binding. The active site is covered by a lid formed by residues 16-28 and 86-100. A comparison of the structure of AIRs kinase with other ribokinase superfamily members suggests that the active site lid and conformational changes that occur upon substrate binding may be advanced features in the evolution of the ribokinase superfamily.

Amines↗

PubMed2004

The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor.

OBJECTIVES: Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene (MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy the endothelial dysfunction and restore endothelium-dependent vasodilatation. The co-existence of genetic polymorphisms in drug metabolizing enzymes, targets, receptors, and transporters may influence the drug efficacy. The purpose of this study was to investigate whether short-term blood pressure control by benazepril, an ACE inhibitor, was modulated by C677T MTHFR gene polymorphism. METHODS AND RESULTS: A total of 444 hypertensive patients, aged 27 to 65 years, without any anti hypertensive therapy within 2 weeks were included. All of them were treated orally with benazepril at a single daily fixed dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. Among them, the frequency of MTHFR C677T genotype CC, CT and TT was 24.3%, 51.8%, and 23.9%, respectively. In a recessive model (CC+CT versus TT genotype), both baseline diastolic blood pressure (DBP) and diastolic blood pressure response (DeltaDBP) were significantly higher in patients with the TT genotype than in those with the CT or CC genotype (P value=0.0076 for DBP, and P value=0.0005 for DeltaDBP). We further divided all patients into three groups based on the tertiles of the DeltaBP distribution. Compared to subjects in the lowest tertile of DeltaDBP, the adjusted relative odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI, 1.4 to 4.9). However, baseline systolic blood pressure (SBP) and SBP response did not significantly associate with MTHFR C677T polymorphism. CONCLUSIONS: Our finding suggests that MTHFR C667T polymorphism modulated baseline DBP and DBP responsiveness by short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.

Adult↗

PubMed2004

Hypertensive patients from two rural Chinese counties respond differently to benazepril: the Anhui Hypertension Health Care Study.

PURPOSE: Essential hypertension, as a complex disorder with unknown etiology cause, is a major public health problem worldwide. Patients need constant drug therapy to maintain their blood pressure in a normal range. However, the current facts suggest that the treatment is not optimized in a large number of patients, and as a result they are at risk for compliance resulting in uncontrolled blood pressure. Genetic and environmental factors associated with individual variation in response to anti-hypertensive drug remain largely unknown. METHODS: In order to illustrate the existence and to attempt to identify the factors modifying drug effect, we conducted a large-scale follow-up study in two Chinese rural counties differing in both genetic background and residential environment. Hypertensive patients were treated with benazepril, a commonly used angiotensin converting enzyme inhibitor, for 15 days, and the end-point effect was evaluated. RESULTS: We found that there were large and significant differences in drug response between subjects from two counties, even after adjustment for known factors. The responses to benazepril, measured in diastolic blood pressure drop, in male patients from Yuexi was twice as effective as their counterparts from Huoqiu. CONCLUSIONS: These results suggest that adjustment of treatment regimen is necessary to improve efficacy, and it could be done at the population level to make it more feasible and affordable.

Adult↗

PubMed2004

Effects of pluronic P85 on GLUT1 and MCT1 transporters in the blood-brain barrier.

PURPOSE: The amphiphilic block copolymer Pluronic P85 (P85) increases the permeability of the blood-brain barrier (BBB) with respect to a broad spectrum of drugs by inhibiting the drug efflux transporter, P-glycoprotein (Pgp). In this regard, P85 serves as a promising component for CNS drug delivery systems. To assess the possible effects of P85 on other transport systems located in the brain, we examined P85 interactions with the glucose (GLUT1) and monocarboxylate (MCT1) transporters. METHODS: Polarized monolayers of primary cultured bovine brain microvessel endothelial cells (BBMEC) were used as an in vitro model of the BBB. 3H-2-deoxy-glucose and 14C-lactate were selected as GLUT1 and MCT1 substrates, respectively. The accumulation and flux of these substrates added to the luminal side of the BBMEC monolayers were determined. RESULTS: P85 has little effect on 3H-2-deoxy-glucose transport. However, a significant decrease 14C-lactate transport across BBMEC monolayers is observed. Histology, immunohistochemistry, and enzyme histochemistry studies show no evidence of P85 toxicity in liver, kidney, and brain in mice. CONCLUSIONS: This study suggests that P85 formulations do not interfere with the transport of glucose. This is, probably, due to compensatory mechanisms in the BBB. Regarding the transport of monocarboxylates, P85 formulations might slightly affect their homeostasis in the brain, however, without any significant toxic effects.

Animals↗

PubMed2004

Comparison of efficacy of reverse remodeling and clinical improvement for relatively narrow and wide QRS complexes after cardiac resynchronization therapy for heart failure.

INTRODUCTION: Cardiac resynchronization therapy (CRT) has been shown to reverse left ventricular (LV) remodeling and improve symptoms in heart failure patients with wide QRS complexes; however, its role in patients with mildly prolonged QRS complexes is unclear. This study investigated if CRT benefited patients with mildly prolonged QRS complexes >120 to 150 ms and explored if the severity of systolic asynchrony determined such a response. METHODS AND RESULTS: Fifty-eight patients (age 66 +/- 11 years, 66% male) who had undergone CRT were studied prospectively. Of these patients, 27 had QRS duration between 120 and 150 ms (group A), and 31 had QRS duration >150 ms (group B). Tissue Doppler echocardiography and clinical assessment were performed at baseline and 3 months after CRT. Both groups had significant reduction of LV volume and increased ejection fraction, +dP/dt, and sphericity index (all P < 0.05). These improvements were greater in group B and were explained by the higher prevalence of systolic intraventricular asynchrony. Significant reverse remodeling (reduction of LV end-systolic volume >15%) was evident in 46% of group A patients and 68% of group B patients. Improvement in clinical endpoints was observed in both groups (all P < 0.01), although the changes in metabolic equivalent and New York Heart Association functional class were greater in group B. In both groups, systolic asynchrony index (TS-SD) was the most important predictor of reverse remodeling (r =-0.78, P < 0.001) and was the only independent predictor in the multivariate model (beta=-1.80, confidence interval =-2.18 to -1.42, P < 0.001); QRS duration was not. A predefined TS-SD value >32.6 ms had a sensitivity of 94% and specificity of 83% to predict reverse remodeling. Improvement of intraventricular asynchrony after CRT was evident only in responders (P = 0.01). CONCLUSION: Improvement of LV remodeling and clinical status is evident after CRT in heart failure patients with QRS duration >120 to 150 ms. These responders are closely predicted by the severity of prepacing intraventricular asynchrony but not QRS duration.

Aged↗

PubMed2004

Beta2 adrenergic receptor gene Arg16Gly polymorphism is associated with therapeutic efficacy of benazepril on essential hypertension in Chinese.

BACKGROUND: There is considerable variability in individual response to antihypertensive agents. The reason for this is not known, but may be related to individual genetic variability. This study examined whether the therapeutic efficacy of benazepril on essential hypertension is modified by beta2 adrenergic receptor gene (ADRB2) Arg16Gly (R16G) polymorphism. METHODS AND RESULTS: We conducted a family-based study of 321 and 610 hypertensive subjects from Yuexi and Huoqiu Counties of Anhui, China, respectively. Both systolic and diastolic blood pressures (SBP and DBP) before and after a 15-day benazepril treatment were measured. ADRB2 R16G genotypes were determined for all subjects. ADRB2 G16 allele frequency was found to be 41.0% and. 47.4% in Huoqiu and Yuexi, respectively. In Yuexi family-based association test (FBAT) revealed that the G16 allele was associated with a greater DBP decrease in response to a 15-day benazepril treatment (Z = 2.12, P = 0.03), and the data were consistent with a dominant inheritance model. A similar trend was observed in Huoqiu Chinese, but the magnitudes of effects were smaller and did not reach statistical significance. The FBAT results were further confirmed by using a generalized estimating equation model. CONCLUSION: Our family-based study provided the first evidence that ADRB2 R16G polymorphism may play an important role in DBP response to benazepril treatment, although the magnitude of the effect appears to be modified by other risk factors such as plasma lipid and glucose profiles.

Adult↗

PubMed2004

Tempol, a nitroxide antioxidant, improves locomotor and histological outcomes after spinal cord contusion in rats.

We have determined whether the nitroxide antioxidant, tempol, can oppose tissue loss and improve recovery of locomotor function following contusion injury of the spinal cord. Contusion injury was produced in rats at the level of T10 with a weight-drop device and locomotor recovery was determined with the 21-point Basso, Beattie and Bresnahan (BBB) scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater in tempol-treated (275 mg/kg i.p., 20 min postinjury) compared to vehicle-treated rats (final BBB scores: 9.1 versus 6.4). Similarly enhanced locomotor recovery was observed with doses of tempol in the range of 138-550, but not 69 mg/kg, and with injection at 48 h postinjury indicating a therapeutic time-window of at least several days. The extent of recovery correlated with measurements of sparing of spinal cord white matter in a region several millimeters in length extending rostrally from the contusion epicenter. In contrast, loss of gray matter was unaffected by tempol treatment. Since tempol acts by scavenging reactive oxygen species (ROS) such as superoxide and hydroxyl radicals, the improved locomotor recovery and spared spinal cord tissue following contusion injury provides evidence of a direct role of ROS-mediated neurodegeneration in spinal cord injury.

Animals↗

PubMed2004

Urticarial erythema associated with IgA myeloma.

We report a case of atypical urticaria associated with IgA multiple myeloma. A 79-year-old man presented with a two-month history of wheal-like erythema, which lasted approximately one week without any response to anti-histamines. Histological examination of a lesion revealed leukocytoclasia as well as perivascular leukocytic infiltration, being consistent with urticarial erythema. Laboratory investigation showed markedly elevated serum IgA concentration and M-protein in serum protein electrophoresis. A bone marrow examination led to a diagnosis of myeloma. An immunofluorescence study failed to detect any IgA deposit in the lesion. However, the wheal-like eruptions disappeared when the IgA myeloma was treated and reappeared when it relapsed. We conclude that this long lasting urticaria was the cutaneous manifestation of IgA myeloma.

Aged↗

PubMed2004

Expression of RPS4 in tobacco induces an AvrRps4-independent HR that requires EDS1, SGT1 and HSP90.

The Arabidopsis RPS4 gene belongs to the Toll/interleukin-1 receptor/nucleotide-binding site/leucine-rich repeat (TIR-NB-LRR) class of plant resistance (R) genes. It confers resistance to Pseudomonas syringae carrying the avirulence gene avrRps4. Transient expression of genomic RPS4 driven by the 35S promoter in tobacco leaves induces an AvrRps4-independent hypersensitive response (HR). The same phenotype is seen after expression of a full-length RPS4 cDNA. This indicates that alternative splicing of RPS4 is not involved in this HR. The extent of HR is correlated with RPS4 protein levels. Deletion analyses of RPS4 domains show the TIR domain is required for the HR phenotype. Mutations in the P-loop motif of the NB domain abolish the HR. Using virus-induced gene silencing, we found that the cell death resulting from RPS4 expression is dependent on the three plant signalling components EDS1, SGT1 and HSP90. All these data suggest that heterologous expression of an R gene can result in activation of cell death even in the absence of its cognate avirulence product, and provides a system for studying the RPS4 domains required for HR.

Alternative Splicing↗

PubMed2004

Proteasomal degradation of caspase-6 in 17beta-estradiol-treated neurons.

In primary cultures of human neurons, 17beta-estradiol (17beta-E2) prevents caspase-6-mediated cell death and induces a caspase inhibitory factor (CIF) inhibiting active caspase-6 (Csp-6) in vitro. Here, we show that treatment of neurons with 17beta-E2 results in a proteasomal-dependent but ubiquitin-independent degradation of endogenous and exogenous active Csp-6 in live neurons and in cell free assays, respectively. We further show that the proteasomal-dependent degradation of Csp-6 is not required for its inhibition. Using several protease inhibitors, we find that leupeptin, E-64, and ALLN prevent inhibition of recombinant active Csp-6 (R-Csp-6) in 17beta-E2-treated neuronal protein extracts. Because all three protease inhibitors have the ability to inhibit cysteine proteases, we believe that a cysteinyl protease activity may be required for 17beta-E2-mediated inhibition of active Csp-6. However, we exclude caspases, calpains, and cathepsins as potential cysteinyl proteases involved in the 17beta-E2-mediated Csp-6 inhibition. The results suggest that a proteolytic activity inhibited by leupeptin, E-64, and ALLN is needed to inhibit Csp-6 and that the inhibited Csp-6 is subsequently degraded by the proteasome. The mechanism of 17beta-E2-mediated inhibition of Csp-6 is different from the ubiquitin-dependent proteasomal degradation of Csp-3 and Csp-7 by XIAP and cIAP2 but consistent with the mechanism of Baculovirus p35 inhibition of caspases.

Calpain↗

PubMed2004

Identification of 18S ribosomal DNA genotype of Acanthamoeba from patients with keratitis in North China.

PURPOSE: To identify the genotype of 18S ribosomal RNA gene (18S rDNA, Rns) of the Acanthamoeba strains isolated from patients with keratitis in northern China. METHODS: The genus-specific primers JDP1 and JDP2 were used for the amplification of the amplimer ASA.S1. With DNA PCR and sequencing, Rns genotypes were identified according to the DF3 sequence variances. RESULTS: Of all 26 DF3 sequences obtained from the 26 Acanthamoeba strains, 18 were unique (69.2%). Of those, 17 were Rns genotype T4 and one was Rns genotype T3. CONCLUSIONS: Most Acanthamoeba strains isolated from keratitis in northern China were Rns genotype T4. The results are in agreement with recent results in the literature.

Acanthamoeba↗

PubMed2004

Cone cell survival and downregulation of GCAP1 protein in the retinas of GC1 knockout mice.

PURPOSE: To examine the spatial and temporal characteristics of cone cell survival and the expression of guanylate cyclase-activating proteins (GCAPs) in the guanylate cyclase (GC)-1 knockout (KO) mouse retina. METHODS: Immunohistochemical analyses with peanut agglutinin and an antibody specific for cone transducin were used to examine cone cell survival in the GC1 KO retina at 4, 5, 9, 16, and 24 weeks of age. Immunohistochemical and Northern and Western blot analyses were used to examine the expression of GCAP1 and GCAP2 in 4- to 5-week-old mice. RESULTS: The number of cone cells appeared normal throughout the superior and inferior retinal regions in 4- and 5-week-old GC1 KO mice but gradually decreased by 6 months. Cone cell loss was exacerbated in the inferior retinal region, with only 2% to 8% remaining by 6 months of age; however, 40% to 70% of the cone cells survived in the superior region at this age. GCAP1 and GCAP2 protein levels were downregulated in GC1 KO retinas at 4 weeks of age and GCAP1 immunostaining was absent from the photoreceptor outer segments. CONCLUSIONS: The results of this study show that the rate of cone cell loss in the GC1 KO mouse is comparable to that previously described in the GUCY1*B chicken and in humans with Leber congenital amaurosis (LCA)-1. The GCAP expression data, when combined with those of previous electrophysiological studies of the GC1 KO mouse retina, provide evidence that GC1-GCAP1 interactions are essential for cone cell function in mice and that GC2 and GCAP2 activities contribute to the rod cell response in the absence of GC1.

Animals↗

PubMed2004

Possibility of the diagnosis of subacute myeloid leukemia for a group of patients with trisomy 8: a report of 34 cases.

The term subacute myeloid leukemia is not present in most hematologic textbooks, but clinically the disease does exist. During the past 13 years, 34 patients with trisomy 8 (+8) and previous diagnoses of refractory anemia with excess blasts in myelodysplastic syndromes were followed and studied in our institute. None of the patients had been given cytotoxic drugs before the leukemia became apparent. Eighteen patients (52.9%) had a history of 3 months to more than 20 years before cytogenetic detection of +8. Abnormalities of blood cell counts were seen in 1 to 3 cell lines, with a median blast cell percentage in the bone marrow of 8% (range, 5%-19%). At a median follow-up period of 21.5 months (range, 3-129 months), the median overall survival time was 20 months for all of the patients with +8, including the patients with chromosome abnormalities in addition to +8. In the group with +8 only, 11 (45.8%) of the 24 patients developed frank leukemia, and 9 of these 11 patients died. In conclusion, our results showed that this group of +8 patients had multilineage abnormalities in blood cell counts and increased numbers of blasts in the bone marrow. The diseases of these patients manifested an insidious onset and a subacute but progressive clinical course, and they all had cytogenetic clonal changes with +8. These facts suggest that this group of +8 patients all had evidence of a leukemic clone, and their conditions might conform to the diagnosis of subacute myeloid leukemia.

Adult↗