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Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 325 records · Page 18Linked to original sources

[Genotype-phenotype correlation in Chinese patients with retinitis pigmentosa due to rhodopsin mutation].

PURPOSE: To investigate the genotype-phenotype correlation in Chinese patients with retinitis pigmentosa caused by rhodopsin gene mutation. METHODS: On the basis of the onset of symptoms, degree of morphological changes and progression of visual disability in three (3/83) patients with identified mutations, the correlation of the phenotype with the corresponding mutations was assessed. RESULTS: There was a certain degree of allele-specificity. Severe form of retinitis pigmentosa was found in patients with mutation in the cytoplasmic domain and mild form of retinitis pigmentosa in patients with mutation in the intradiscal domain. CONCLUSION: Although there is a certain relation between the mutant rhodopsin and ocular manifestation, we need to accumulate more materials before relating a rhodopsin mutation to a specific phenotype.

Adult↗

[Cloning and sequencing of human papillomavirus 16 L1 gene from cervical carcinoma tissues of Chinese women].

OBJECTIVE: Human papillomavirus type 16 (HPV16) is highly related with the development of cervical carcinoma. HPV16 late gene L1 encodes its main capsid protein. This study is to analyze the whole sequence of L1 gene of HPV16 of the Chinese isolates. METHODS: Three samples of HPV16 L1 gene were amplified from cervical carcinoma tissues of Chinese patients by PCR and then cloned and sequenced. RESULTS: There were four sites in nucleic acid sequences of all three HPV16 L1 fragments were different from the originally reported sequence of HPV16 and the differed sequences had changed the triplet codes, therefore, subsequently changed the amino acids it coded. CONCLUSION: The results showed that some mutation had taken place in the nucleotide sequence of L1 gene of HPV16 obtained from the cervical carcinoma tissues of Chinese women.

Capsid Proteins↗

[Immunohistochemical and pathological study of capsaicin in the treatment of rabbit animal model with allergic rhinitis].

OBJECTIVE: To determine the desensitization effect of capsaicin. METHODS: Toluene-2,4-diisocyanate(TDI) sensitized white rabbits used as animal models of allergic rhinitis were treated with capsaicin. At the end of treatment, the changes in the nasal mucosa were studied by immunohistochemical and pathological methods. RESULTS: Our results showed that the symptoms of allergic rhinitis were remarkably relieved after capsaicin treatment. Immunohistochemical study revealed that substance P immunoreactive fibers in the nasal mucosa showed a marked decrease after capasicin application, but the density and number of SP-IR fibers were significantly increased in the control group. Hematoxylin and eosin staining demonstrated that no edema was found in the nasal mucosa and small vessels were normal after capsaicin application, but edema, vasodilation and inflammatory cell infiltration were discovered in the control group. CONCLUSION: The results suggested that local capsaicin treatment was a selective, and non-traumatic method to induce a long lasting desensitization of the nasal mucosa, to alleviate nasal congestion, rhinorrhea and sneezing, and to reduce the sensory neuron sensitivity of the mucosa.

Administration, Intranasal↗

[Study on the association between squamous cell carcinoma of larynx and HPV subgene by PCR].

OBJECTIVE: To measure the human papilloma virus(HPV) HPV-E1 in squamous cell carcinoma of larynx. METHODS: Polymerase chain reaction(PCR) was used to detect the HPV subgene in 25 specimens of laryngeal carcinoma and 6 normal larynges. RESULTS: Positive expression of HPV-E1 was detected in 17 of 25 cases(68%) with squamous cell carcinoma and all the recurrent cases. However, there was no positive expression of HPV-E1 in the normal larynges (P < 0.01). The expression rate was not significantly different among the histological grad groups. CONCLUSION: HPV-E1 infection was found in laryngeal carcinoma but not related to its histologic grading.

Carcinoma, Squamous Cell↗

Regulation of the activity of IFN-gamma promoter elements during Th cell differentiation.

Before they can deliver their effector functions, CD4+ Th cells must differentiate into Th1 or Th2 subsets. We have prepared reporter transgenic mice that express the luciferase gene under the control of proximal (prox.IFN-gamma) and distal (dist.IFN-gamma) regulatory elements from the IFN-gamma promoter to permit investigation of mechanisms that regulate IFN-gamma gene transcription during Th cell differentiation. Precursor Th cells (pTh) contain high levels of cAMP response element binding protein-activation transcription factor-1 (CREB-ATF1) proteins that bind these promoter elements from the IFN-gamma gene, and these cells fail to express promoter activity. Restimulated effector Th (eTh) cells have reduced levels of CREB-ATF1 proteins, their nuclear extracts exhibit reduced CREB-ATF1 binding and greater Jun and Jun-ATF2 binding to dist.IFN-gamma), and eTh cells express promoter activity. CREB directly competes with effector T cell nuclear proteins for dist.IFN-gamma binding, and overexpression of CREB inhibits both prox.IFN-gamma- and dist.IFN-gamma-directed transcription in Jurkat T cells. IL-12-stimulated Thl differentiation increases dist.IFN-gamma activity in restimulated eTh1 cells; eTh1 nuclear extracts form increased levels of Jun-ATF2-dist.IFN-gamma complexes. Taken together, these data suggest that both de-repression and trans-activation contribute to the induction of IFN-gamma gene transcription during Th1 differentiation.

Animals↗

Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia.

Focal cerebral ischemia is associated with expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), enzymes whose reaction products contribute to the evolution of ischemic brain injury. We tested the hypothesis that, after cerebral ischemia, nitric oxide (NO) produced by iNOS enhances COX-2 activity, thereby increasing the toxic potential of this enzyme. Cerebral ischemia was produced by middle cerebral artery occlusion in rats or mice. Twenty-four hours after ischemia in rats, iNOS-immunoreactive neutrophils were observed in close proximity (<20 micrometer) to COX-2-positive cells at the periphery of the infarct. In the olfactory bulb, only COX-2 positive cells were observed. Cerebral ischemia increased the concentration of the COX-2 reaction product prostaglandin E2 (PGE2) in the ischemic area and in the ipsilateral olfactory bulb. The iNOS inhibitor aminoguanidine reduced PGE2 concentration in the infarct, where both iNOS and COX-2 were expressed, but not in the olfactory bulb, where only COX-2 was expressed. Postischemic PGE2 accumulation was reduced significantly in iNOS null mice compared with wild-type controls (C57BL/6 or SV129). The data provide evidence that NO produced by iNOS influences COX-2 activity after focal cerebral ischemia. Pro-inflammatory prostanoids and reactive oxygen species produced by COX-2 may be a previously unrecognized factor by which NO contributes to ischemic brain injury. The pathogenic effect of the interaction between NO, or a derived specie, and COX-2 is likely to play a role also in other brain diseases associated with inflammation.

Animals↗

Temporal characteristics of the protective effect of aminoguanidine on cerebral ischemic damage.

We investigated the temporal profile of the reduction in focal cerebral ischemic damage exerted by aminoguanidine (AG), an inhibitor of inducible nitric oxide synthase (iNOS). In anesthetized spontaneously hypertensive rats, the middle cerebral artery (MCA) was occluded distal to the origin of the lenticulostriate arteries. Rats were treated with vehicle (saline) or AG (100 mg kg-1, i.p.) immediately after MCA occlusion and, thereafter, two times per day. Rats were sacrificed 1(n = 7), 2(n = 8), 3 (n = 6) or 4 days (n = 5) after MCA occlusion. Injury volume (mm3) was determined in thionin-stained sections using an image analyzer. Volumes were corrected for ischemic swelling. Administration of AG up to 2 days after MCA occlusion did not reduce cerebral ischemic damage (p < 0.05 from vehicle; t-test). Treatment for a longer period decreased injury volume, the reduction averaging 21 +/- 5% at 3 days (p < 0.05) and 30 +/- 9% at 4 days (p < 0.05). Aminoguanidine did not affect ischemic brain swelling (p > 0.05). Administration of AG did not substantially modify arterial pressure, arterial blood gases, pH, hematocrit, plasma glucose and rectal temperature. We conclude that the protective effect of AG is time-dependent and occurs only when the drug is administered for longer than 2 days, starting after induction of ischemia. Because iNOS enzymatic activity develops more than 24 h after MCA occlusion [C. Iadecola, X. Xu, F. Zhang, E.E. El-Fakahany, M.E. Ross, Marked induction of calcium-independent nitric oxide synthase activity after focal cerebral ischemia, J. Cereb. Blood Flow, Metab. 14 (1995) 52-59; C. Iadecola, F. Zhang, X. Xu, R. Casey, M.E. Ross, Inducible nitric oxide synthase gene expression in brain following cerebral ischemia, J. Cereb. Blood Flow Metab. 15 (1995) 378-384.], the data support the hypothesis that the protective effect of AG is medicated by inhibition of iNOS in the post-ischemic brain.

Animals↗

Seasonal rainfall variability, the incidence of hemorrhagic fever with renal syndrome, and prediction of the disease in low-lying areas of China.

To investigate determinants of hemorrhagic fever with renal syndrome (HFRS) in low-lying areas of China, the authors studied Chuigang and Wanggang communities in Anhui Province. These adjacent farming communities have a population of about 100,000. Data were collected from the two communities in 1961-1977 and from Yingshang County in 1983-1995; information covered the incidence of HFRS, amount of precipitation, differences in the water level of the Huai River, density of Apodemus agrarius, autumn crop production, and areas of inundated farmland. Correlation and multiple linear regression analyses were used to estimate the relation between seasonal rainfall, density of mice, occupational factors, and occurrence of the disease. Associations were observed between the incidence of HFRS and the amount of precipitation, the water level of the Huai River, and the areas of inundated farmland in Chuigang community. The smaller the water-level difference, the less farmland was inundated and the higher the incidence of HFRS. In Wanggang community, the density of A. agrarius (r1=0.63, p=0.02), the water-level difference in the Huai River (r2=-0.81, p=0.007), and crop production (r3=0.96, p=0.005) were correlated with the incidence of HFRS. The regression analyses based on Wanggang community suggested that these indexes could be used as predictive variables, and the results from the model were well calibrated with the actual incidence of HFRS in that community (R2=0.88, p < 0.01) and Yingshang County (R2=0.91, p < 0.01).

Animals↗

Targeting immune response induction with cochleate and liposome-based vaccines.

The immune response generated by infection with a pathogenic organism, or by vaccination with a live attenuated or whole killed pathogen, often does not stimulate optimal protection against that organism. Lipid matrix-based subunit vaccines can be used to produce custom-designed vaccines, that elicit desired immune responses targeted to specific parts of the pathogen that are relevant to protection. Harmful or competitive responses can be minimized or avoided. Earlier work with liposomes has allowed the development of a new class of subunit vaccines called cochleate delivery vehicles, whose structure and properties are very different from liposomes. Protein and DNA cochleates are highly effective vaccines when given via mucosal or parenteral routes, including oral, intranasal, intramuscular, or subcutaneous. Strong, long-lasting, mucosal and circulating, antibody and cell-mediated responses are generated. Protection from challenge with live viruses following oral or intramuscular administration has been achieved.

Journal Article↗

The induction of acute phase proteins by lipopolysaccharide uses a novel pathway that is CD14-independent.

LPS (endotoxin) and proinflammatory cytokines (IL-6, IL-1, and TNF-alpha) are potent inducers of acute phase proteins (APP). Since LPS induces high levels of these cytokines after its interaction with CD14, a protein expressed on the surface of monocytes and neutrophils, it has been assumed that CD14 mediates the LPS induction of APP expression. To test this hypothesis, CD14-deficient and control mice were injected with low doses of LPS, and the expression of several APP that are normally up-regulated by LPS was measured. CD14-deficient mice showed no alteration in the induction of APP, including serum amyloid A, LPS-binding protein, fibrinogen, or ceruloplasmin; in contrast, C3H/HeJ mice, which carry a mutation in the Lps gene, do not up-regulate the expression of these proteins. These studies show that the up-regulation of APP by LPS utilizes a non-CD14 receptor and requires a functional Lps gene.

Acute-Phase Proteins↗

Thermodynamics of membrane partitioning for a series of n-alcohols determined by titration calorimetry: role of hydrophobic effects.

Recent studies have shown that the traditional paradigm relying on hydrophobic effects is not adequate to describe membrane partitioning of amphiphilic solutes. To elucidate the thermodynamics and determine the role of the hydrophobic effect in the partitioning of small amphiphilic molecules into lipid bilayers, we have used titration calorimetry to directly measure the enthalpy, partition coefficients, and heat capacity change for the partitioning of a series of n-alcohols into lipid bilayers of several lipid compositions. The incremental thermodynamic quantities have been compared with model compound data for partitioning into bulk hydrocarbon solvents. We have found that there is a large negative heat capacity change upon partitioning, indicating a major contribution from the dehydration of nonpolar solute moieties; however, these hydrophobic effects also involve changes in lipid interactions with water in the interfacial region of the bilayer. In addition, we have found that the enthalpy effects are large, indicating that the partitioning process is accompanied by significant changes in the intralipid interactions within the bilayer. Cholesterol has a large effect on partitioning thermodynamics, making both the enthalpy and entropy contributions significantly more positive, resulting in a relatively small net decrease in the negative free energy of partitioning. These results demonstrate that while hydrophobic interactions play a major role in partitioning, the process is considerably more complex than the partitioning of model compounds between water and bulk hydrocarbons, with major contributions coming from changes in the structure and thermodynamic state of the bilayer, including the interfacial region. The results are discussed in terms of both the thermodynamics of partitioning and the role of lipid properties in membrane function. Our results support a paradigm for membrane structure and function in which the thermodynamic state, which is a function of lipid composition, temperature, and dissolved solutes, is a critical membrane property.

1,2-Dipalmitoylphosphatidylcholine↗

Lack of association between schizophrenia and HLA DQB1 alleles in a Swedish sample.

Three studies have reported a negative genetic association between schizophrenia and HLA DQB1*0602, an allele of the human leucocyte antigen (HLA) DQB1*06 gene. In a sample of ethnic all homogeneous Caucasians living in Sweden, the frequency of HLA DQB1 alleles in patients with schizophrenia (n = 124) was compared with that in a control group (n = 85). No significant differences were found. Together with previous investigations, the present study indicates that the reported genetic association of DQB1*0602 with schizophrenia may be limited to non-Caucasians.

Adult↗

In vitro selection of bacteriophage phi29 prohead RNA aptamers for prohead binding.

Prohead RNA (pRNA) of the Bacillus subtilis bacteriophage phi29 is needed for in vitro packaging of DNA-gene product 3 (DNA-gp3). Residues 22-84 of the 174-base pRNA bind the portal vertex of the prohead, the site of DNA packaging. To define the nucleotides of pRNA needed for prohead binding and DNA-gp3 packaging and to seek biologically active variants of pRNA, segments of pRNA were randomized to obtain vast repertoires of RNA molecules. RNA aptamers, ligands best suited for prohead binding, were obtained by multiple rounds of in vitro selection. Evolution of pRNA aptamers was followed by a competition binding assay and nucleotide sequencing, and mutants were tested for DNA-gp3 packaging. Aptamers selected following randomization of the E stem and loop and a part of the C-E loop that were active in DNA-gp3 packaging were invariably wild-type. DNA-gp3 packaging activity also required nucleotides G82 and G83 that form base pairs intermolecularly with C47 and C48 to produce a novel hexameric oligomer of pRNA. The only mutant aptamers that retained full DNA-gp3 packaging activity showed changes of the U residues at positions 81, 84, and 85 of the D loop. Thus, the in vitro selections essentially recapitulated the natural evolution of pRNA.

Bacillus Phages↗

Dihydroxy bile acids activate the transcription of cyclooxygenase-2.

Bile acids, endogenous promoters of gastrointestinal cancer, activate protein kinase C (PKC) and the activator protein-1 (AP-1) transcription factor. Because other activators of PKC and AP-1 induce cyclooxygenase-2 (COX-2), we determined the effects of bile acids on the expression of COX-2 in human esophageal adenocarcinoma cells. Treatment with the dihydroxy bile acids chenodeoxycholate and deoxycholate resulted in an approximately 10-fold increase in the production of prostaglandin E2 (PGE2). Enhanced synthesis of PGE2 was associated with a marked increase in the levels of COX-2 mRNA and protein, with maximal effects at 8-12 and 12-24 h, respectively. In contrast, neither cholic acid nor conjugated bile acids affected the levels of COX-2 or the synthesis of PGE2. Nuclear run-off assays and transient transfections with a human COX-2 promoter construct showed that induction of COX-2 mRNA by chenodeoxycholate and deoxycholate was due to increased transcription. Bile acid-mediated induction of COX-2 was blocked by inhibitors of PKC activity, including calphostin C and staurosporine. Treatment with bile acid enhanced the phosphorylation of c-Jun and increased binding of AP-1 to DNA. These data are important because dihydroxy bile acid-mediated induction of COX-2 may explain, at least in part, the tumor-promoting effects of bile acids.

Bile Acids and Salts↗

Absence of immunogenicity of diaspirin cross-linked hemoglobin in humans.

Diaspirin cross-linked hemoglobin (DCLHb) is an intramolecularly cross-linked hemoglobin-based oxygen carrier being developed as a therapy for acute blood loss. We report here the absence of immunogenicity of DCLHb in patients enrolled in phase II and III clinical trials of DCLHb. Two very sensitive immunoassays, an enzyme-linked immunosorbent assay (ELISA) and a Western blot assay, were developed and validated for this assessment. The DCLHb-antibodies used in these assays were raised in monkeys, had similar affinities for DCLHb and native human hemoglobin (SFHb), and showed cross-reactivity for subunits of DCLHb and SFHb on the Western blot, suggesting that these antibodies were elicited as a xenogenic response to the protein. In the ELISA, the optical density of a patient sample exposed to DCLHb-coated wells was compared with that of the patient sample exposed to carbonate buffer-coated wells; an optical density ratio of 1.4 was established for discriminating between a positive (reactive) or negative DCLHb antibody response. To date, all of the more than 300 patient specimens (preinfusion and postinfusion) from clinical trials have exhibited a ratio of less than 1.4, confirming the lack of preexisting antibodies to DCLHb and clearly showing the absence of DCLHb antibodies after exposure to this new biologic entity. There has been no requirement for use of the confirmatory Western blot assay. Taken together, the results from this study indicate DCLHb is not immunogenic in humans at doses evaluated clinically.

Animals↗

Dopamine receptor genetic variation, psychosis, and aggression in Alzheimer disease.

OBJECTIVE: To examine if selected polymorphisms in the dopamine receptor genes DRD1, DRD2, DRD3, and DRD4 are associated with the presence of psychosis or aggressive behavior in patients with Alzheimer disease (AD). DESIGN: A cohort of patients with AD were longitudinally evaluated for behavioral symptoms and classified with regard to the presence of psychotic symptoms and physical aggression. SETTING: Alzheimer's Disease Research Center. PATIENTS: Two hundred seventy-five elderly outpatients diagnosed as having probable AD. RESULTS: Among white patients, psychosis and aggression were both significantly more frequent in DRD1 B2/B2 homozygotes (P < .02), while psychosis was significantly more frequent in DRD3 1/1 or 2/2 homozygotes (P < .05). The joint risk for psychosis due to the DRD1 and DRD3 polymorphisms exceeded the risks due to either locus alone, suggesting an interaction. Neither the DRD2 S311C polymorphism nor the presence of long alleles for the DRD4 exon III repeat sequence was associated with psychosis or aggression. CONCLUSIONS: Genetic variation in DRD1 and DRD3 genes may act to modify the course of AD, predisposing to the development of psychotic or aggressive symptoms. Confirmation in other samples of patients with AD is required.

Aged↗

In vivo investigation of blood compatibility of titanium oxide films.

Titanium oxide films were synthesized by ionbeam-enhanced deposition. The films were prepared by depositing titanium atoms and simultaneously bombarding them with Xe+ ions at an energy of 40 keV in an O2 environment. An in vivo investigation, which entailed implanting low-temperature isotropic pyrolytic carbon (LTI carbon) cylinders, widely used to fabricate artificial heart valves, and titanium-oxide-coated LTI carbon cylinders with diameters of 5 mm and thicknesses of 0.5 mm into the ventral aorta of dogs for 14 days, showed that the amount of thrombus on the titanium-oxide-coated LTI carbon was much less than that formed on the surface of LTI carbon alone. Scanning electron microscopy (SEM) was used to observe the morphology of thrombus. On the titanium oxide films no platelet aggregation was found, almost no red blood cells were damaged, and almost no fibrin was found on the surface. However, all three characteristics were found on the surface of LTI carbon alone, proving that the blood compatibility of titanium oxide films is better than that of LTI carbon and titanium-oxide-coated LTI carbon.

Animals↗