Biomedical subjects

T Zhang

Publications and source records attributed to T Zhang.

At least 91 records · Page 5Linked to original sources

PubMed2001

Treatment with cathepsin L inhibitor potentiates Th2-type immune response in Leishmania major-infected BALB/c mice.

Prior to the activation of CD4 (+) T cells, exogenous proteins must be digested by endo/lysosomal enzymes in antigen-presenting cells (APC) to produce antigenic peptides that are able to be presented on class II molecules of the MHC. Studies described here inspect the functional significance of cathepsin L inhibition for antigen processing and T (h) 1/T (h) 2 differentiation in experimental leishmaniasis. We first demonstrated using in vitro systems that cathepsin L is one of the candidate endo/lysosomal enzymes in processing of soluble Leishmania antigen (SLA) and that its specific inhibitor, CLIK148, modulated the processing of SLA. BALB/c mice are known to be susceptible to infection with Leishmania major. Interestingly, treatment of BALB/c mice with CLIK148 exacerbated the infection by enhancing the development of SLA-specific T (h) 2-type response such as production of IL-4 and generation of T (h) 2-dependent specific IgE/IgG1 antibodies. Moreover, addition of CLIK148 in incubation of a SLA-specific CD4 (+) T cell line with APC up-regulated the production of IL-4. However, CLIK148 did not exert any direct influence on the function of T cells themselves. Taken together, these findings suggest that treatment of host mice with CLIK148 affects the processing of SLA in APC, resulting in the potentiation of T (h) 2-type immune responses and thus leading to exacerbation of the infection. Furthermore, endo/lysosomal cathepsin L was found to be functionally distinct from previously described cathepsins B and D.

Adjuvants, Immunologic↗

PubMed2001

Epidemiologic and clinical characteristics of Kawasaki disease in Shaanxi Province, China, 1993-1997.

The objective of this paper is to describe the epidemiological and clinical characteristics of Kawasaki disease (KD) in Shaanxi Province, China during the 5-year period from January 1993 to December 1997. A province-wide epidemiological survey on KD was made by the China-Japan Kawasaki Disease Study Group. The questionnaire form and the diagnostic criteria of KD, which were prepared by the Japan Kawasaki Disease Research Committee and translated into Chinese, were sent to the departments of pediatrics of all the hospitals with 100 beds or more in Shaanxi province. All the KD patients who were diagnosed during the observation period from 1993 to 1997 were asked to take part in this survey. The databases of reported KD in this survey were analysed at the Department of Pediatrics of the Shaanxi Provincial People's Hospital, Xi'an, China. All the patients that satisfied the diagnostic criteria were included in the report. A total of 105 (70 per cent) hospitals responded and 376 cases of KD were confirmed. More cases were reported in 1993 and 1994. Of the total patients reported, 69 per cent were children under 3 years old with a male to female ratio of 1.6:1. The proportion of patients with cardiac sequelae was 19 per cent with a male to female ratio of 3:1. There were four fatal cases with a fatality rate of 1 per cent. It is concluded that KD is common in China. Continuous surveillance is necessary to maintain high awareness of KD so as to find possible risk factors and their association with the disease.

Adolescent↗

PubMed2001

Comparative DNA sequence analysis of mouse and human protocadherin gene clusters.

The genomic organization of the human protocadherin alpha, beta, and gamma gene clusters (designated Pcdh alpha [gene symbol PCDHA], Pcdh beta [PCDHB], and Pcdh gamma [PCDHG]) is remarkably similar to that of immunoglobulin and T-cell receptor genes. The extracellular and transmembrane domains of each protocadherin protein are encoded by an unusually large "variable" region exon, while the intracellular domains are encoded by three small "constant" region exons located downstream from a tandem array of variable region exons. Here we report the results of a comparative DNA sequence analysis of the orthologous human (750 kb) and mouse (900 kb) protocadherin gene clusters. The organization of Pcdh alpha and Pcdh gamma gene clusters in the two species is virtually identical, whereas the mouse Pcdh beta gene cluster is larger and contains more genes than the human Pcdh beta gene cluster. We identified conserved DNA sequences upstream of the variable region exons, and found that these sequences are more conserved between orthologs than between paralogs. Within this region, there is a highly conserved DNA sequence motif located at about the same position upstream of the translation start codon of each variable region exon. In addition, the variable region of each gene cluster contains a rich array of CpG islands, whose location corresponds to the position of each variable region exon. These observations are consistent with the proposal that the expression of each variable region exon is regulated by a distinct promoter, which is highly conserved between orthologous variable region exons in mouse and human.

Animals↗

PubMed2001

Nippocystatin, a cysteine protease inhibitor from Nippostrongylus brasiliensis, inhibits antigen processing and modulates antigen-specific immune response.

During infection, parasites evade the host immune system by modulating or exploiting the immune system; e.g., they suppress expression of major histocompatibility complex class II molecules or secrete cytokine-like molecules. However, it is not clear whether helminths disturb the immune responses of their hosts by controlling the antigen-processing pathways of the hosts. In this study, we identified a new cysteine protease inhibitor, nippocystatin, derived from excretory-secretory (ES) products of an intestinal nematode, Nippostrongylus brasiliensis. Nippocystatin, which belongs to cystatin family 2, consists of 144 amino acids and is secreted as a 14-kDa mature form. In vivo treatment of ovalbumin (OVA)-immunized mice with recombinant nippocystatin (rNbCys) profoundly suppressed OVA-specific proliferation of splenocytes but not non-antigen-specific proliferation of splenocytes. OVA-specific cytokine production was also greatly suppressed in rNbCys-treated mice. Although the serum levels of both OVA-specific immunoglobulin G1 (IgG1) and IgG2a were not affected by rNbCys treatment, OVA-specific IgE was preferentially downregulated in rNbCys-treated mice. In vitro rNbCys inhibited processing of OVA by lysosomal cysteine proteases from the spleens of mice. Mice with anti-nippocystatin antibodies became partially resistant to infection with N. brasiliensis. Based on these findings, N. brasiliensis appears to skillfully evade host immune systems by secreting nippocystatin, which modulates antigen processing in antigen-presenting cells of hosts.

Amino Acid Sequence↗

PubMed2001

Use of chromatin immunoprecipitation to clone novel E2F target promoters.

We have taken a new approach to the identification of E2F-regulated promoters. After modification of a chromatin immunoprecipitation assay, we cloned nine chromatin fragments which represent both strong and weak in vivo E2F binding sites. Further characterization of three of the cloned fragments revealed that they are bound in vivo not only by E2Fs but also by members of the retinoblastoma tumor suppressor protein family and by RNA polymerase II, suggesting that these fragments represent promoters regulated by E2F transcription complexes. In fact, database analysis indicates that all three fragments correspond to genomic DNA located just upstream of start sites for previously identified mRNAs. One clone, ChET 4, corresponds to the promoter region for beclin 1, a candidate tumor suppressor protein. We demonstrate that another of the clones, ChET 8, is strongly bound by E2F family members in vivo but does not contain a consensus E2F binding site. However, this fragment functions as a promoter whose activity can be repressed by E2F1. Finally, we demonstrate that the ChET 9 promoter contains a consensus E2F binding site, can be activated by E2F1, and drives expression of an mRNA that is upregulated in colon and liver tumors. Interestingly, the characterized ChET promoters do not display regulation patterns typical of known E2F target genes in a U937 cell differentiation system. In summary, we have provided evidence that chromatin immunoprecipitation can be used to identify E2F-regulated promoters which contain both consensus and nonconsensus binding sites and have shown that not all E2F-regulated promoters show identical expression profiles.

Apoptosis Regulatory Proteins↗

PubMed2001

A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain.

The p53 protein is related by sequence homology and function to the products of two other genes, p63 and p73, that each encode several isoforms. We and others have discovered previously that certain tumor-derived mutants of p53 can associate and inhibit transcriptional activation by the alpha and beta isoforms of p73. In this study we have extended these observations to show that in transfected cells a number of mutant p53 proteins could bind and down-regulate several isoforms not only of p73 (p73 alpha, -beta, -gamma, and -delta) but also of p63 (p63 alpha and -gamma; Delta Np63 alpha and -gamma). Moreover, a correlation existed between the efficiency of p53 binding and the inhibition of p63 or p73 function. We also found that wild-type p63 and p73 interact efficiently with each other when coexpressed in mammalian cells. The interaction between p53 mutants and p63 or p73 was confirmed in a physiological setting by examining tumor cell lines that endogenously express these proteins. We also demonstrated that purified p53 and p73 proteins interact directly and that the p53 core domain, but not the tetramerization domain, mediates this interaction. Using a monoclonal antibody (PAb240) that recognizes an epitope within the core domain of a subset of p53 mutants, we found a correlation between the ability of p53 proteins to be immunoprecipitated by this antibody and their ability to interact with p73 or p63 in vitro and in transfected cells. Based on these results and those of others, we propose that interactions between the members of the p53 family are likely to be widespread and may account in some cases for the ability of tumor-derived p53 mutants to promote tumorigenesis.

Antibodies, Monoclonal↗

PubMed2001

Degradation and drug delivery properties of poly(1,4-cyclohexanedicarboxylic anhydride).

Polyanhydrides for drug-controlled release systems from cis- and trans-1,4-cyclohexanedicarboxylic acid (1,4-CHDA) were synthesized by melt polycondensation. The degradation of polymers was estimated by weight loss in 0.1 mol l(-1), pH 7.4 phosphate buffer at 37 degrees C. The drug delivery was conducted in the same buffer. The results show that the different polymers lost weight over 150-360 h, and fine surface erosion was investigated. The different conformation of CHDA has an obvious influence on the degradation of polyanhydrides due to their different crystallinity, with higher crystallinity samples degrading much more slowly. The incorporation of adipic acids into the poly(CHDA) can obviously accelerate the degradation and the introduction of -CH2- segments increased the flexibility of polyanhydride backbone and accelerated the degradation rate. In vitro delivery experiments show that Bruffen was completely released in about 10 days from a melting mold disk with a fine linear delivery curve.

Anhydrides↗

PubMed2001

Incidence survey of Kawasaki disease in 1997 and 1998 in Japan.

OBJECTIVE: To describe the results of a nationwide epidemiologic survey of Kawasaki disease for the 2-year period 1997 and 1998. DESIGN: We sent a questionnaire to all hospitals with 100 beds or more throughout Japan (2663 hospitals) requesting data on patients with Kawasaki disease. Study items included name, sex, date of birth, date of initial hospital visit, diagnosis, address, recurrence, sibling cases, gammaglobulin treatment, and cardiac lesion in the acute stage or 1 month after onset. RESULTS: Of the 2663 hospitals, 68.5% responded, reporting 12 966 patients-7489 males and 5477 females. Of the total patients reported, 6373 (incidence rate of 108.0 per 100 000 children <5 years old) occurred in 1997, and 6593 (111.7) in 1998. More than one half of the patients (54.9%) were <2 years old and 81.6% were <4 years old. In males, the incidence rates of cardiac lesions were 27.2 in the acute stage and 10.1 a month after onset. In females, the rates were 16.7 and 5.2, respectively. The incidence rates of cardiac lesions were highest in the youngest age group (<6 months old) both in the acute stage and 1 month after onset. The rates decreased with increasing ages. Although frequency of giant aneurysms was not high at the acute stage, it did not decrease 1 month after onset. CONCLUSION: The incidence rates have been steadily increasing for 11 years since 1987. The rate in 1998 was over 1.5 times higher than that in 1987. The age and sex distributions were identical in each survey. Although most of the cardiac lesions at the acute stage decreased to half or less 1 month after onset, giant aneurysms did not decrease and existed persistently after 1 month.

Age Distribution↗

PubMed2001

The profiles of Kawasaki disease in China.

Kawasaki disease in China was described for the first time in 1976 in Taiwan, and in 1978 in mainland, respectively. Questionnaire surveys had been conducted in both of the area of China and showed that the Kawasaki disease patients increased year by year. No data on incidence rates were available for these surveys because the problem of representativeness. However, it showed that there were many similar characteristics of Kawasaki disease in China comparing with those in Japan. Although a series of infectious agents were suspected, the etiology of Kawasaki disease remained unclear. High dose of gamma globulin treatment was also adopted commonly in China.

Child↗

PubMed2001

Role of innate immune cells in protection against Toxoplasma gondii at inflamed site.

The intraperitoneal infection with Toxoplasma gondii (T. gondii) caused accumulation of gamma delta T, NK, NK1.1+T-like (NKT) cells at inflamed sites. To clarify the roles of these cells in protection against T. gondii at the inflamed sites, BALB/c mice were depleted of gamma delta T, NK, NK and NKT cells by treatment with antibody against TCR-gamma delta, asialoGM1 or Interleukin-2 receptor beta-chain (IL-2 R beta), respectively, prior to infection. Mice treated with anti-TCR-gamma delta monoclonal antibody (mAb) became more susceptible to infection, whereas mice treated with anti-IL-2R beta mAb acquired resistance. Treatment with anti-asialoGM1 Ab showed no effect. We previously reported that heat shock protein 65 (HSP65) in macrophages induced by gamma delta T cells plays an essential role in protective immunity against T. gondii infection, by preventing apoptotic death of infected macrophages. In the present study, we showed that treatment with anti-IL-2R beta mAb, but not with anti-asialoGM1 Ab, enhanced the HSP65 induction in macrophages, and inhibited Interleukin-4 (IL-4) expression in nonadherent peritoneal exudate cells. Furthermore, neutralization of endogenous IL-4 by anti-IL-4 mAb enhanced the HSP65 induction in macrophages. These findings suggest that NKT cells, but not NK cells, negatively regulate the protective immunity against T. gondii infection possibly by producing IL-4 and suppressing HSP65 induction.

Animals↗

PubMed2001

[Investigation on the mechanics of adhesion to the selective extracellular matrix coated surfaces of lung cancer cells].

The adhesion properties of tumor cells with extracellular matrix(ECM) are closely associated with their invasion and metastasis. Our work reported here was intended reveal the relevant biomechanical and biorheological manifestations of human lung cancer. Using micropipette aspiration technique, we investigated quantitatively the adhesive mechanics properties of high metastatic human giant cell carcinoma(PG) cells as well as low metastatic adenocarcinoma(PAa) cells of lung based on cell culture in vitro. The results showed that the adhesion forces of PAa and PG cells to collagen IV were significantly higher than those to glass surfaces, but at the lower concentrations(1.00 microgram/ml and 2.00 micrograms/ml) of collagen IV, the amplitude for the increase of adhesion forces of PG cells were less than the amplitude for that of PAa cells, and most of the adhesion force values of PAa cells to the coated surfaces of incorporation of laminin along with 2 micrograms/ml collagen IV were significantly greater than those of PG cells. At the lower concentrations(0.625 microgram/ml for PAa cells, and 0.625 microgram/ml, 1.25 micrograms/ml for PG cells) of laminin tested, the adhesion force values of PAa and PG cells all decreased, but the amplitude and level for the decreased values of adhesion forces of PG cells were greater than those for the PAa cells. In conclusion, the adhesive and proteolytic behaviour of cancer cells to extracellular matrix might be mediated mainly by tumor cell membrane receptors such as integrin receptors and laminin receptors, it might affect the biological characteristics and the metastasis of the tumor cells. The results may benefit to explain some questions in biomechanical views about how the highly metastatic PG cells are prone to migration and invasion.

Adenocarcinoma↗

PubMed2001

Excitatory amino acids in cerebrospinal fluid of patients with acute head injuries.

BACKGROUND: The excitatory amino acids (EAAs) glutamate (Glu) and aspartate (Asp) play a role in the pathogenesis of postischemic and posttraumatic brain insult. The changes of EAAs in cerebrospinal fluid (CSF) of patients with traumatic brain injury are incompletely understood. METHODS: We used reversed-phase HPLC with precolumn derivatization with o-phthalaldehyde and fluorescence detection to measure Glu and Asp in CSF of 42 patients with acute head injury and 9 control adults without neurologic diseases. We assessed the Glasgow Coma Scale (GCS) on admission, the main lesion patterns on computed tomography (CT) scan within 24 h post trauma, and the Glasgow Outcome Scale (GOS) 3 months post injury. RESULTS: The mean concentrations of Glu and Asp in CSF in the brain-injured group were significantly higher than those of the control group (Glu, P <0.001; Asp, P <0.05). In patients admitted within 24 h after severe injury (n = 13), peak Glu values appeared within 48 h in 11 patients (85%), and the mean value remained higher than control values at day 7 (P <0.02). The concentrations of EAAs were higher in patients with severe injuries (GCS < or =8) than in those with milder injuries (Glu, P <0.001; Asp, P <0.05). GCS and peak EAAs correlated negatively (Glu, rs = -0.5706, P <0.001; Asp, rs = -0.5503, P <0.001). The patients with focal brain contusion on initial CT scan (n = 8) had a significantly lower peak Glu value than the patients with other patterns (n = 8-15; P <0.02 to 0.001). The peak value of EAAs in the poor-outcome group (including severe disability, vegetative state, and death) was significantly higher than in the good-outcome group (good recovery and moderate disability; Glu, P <0.001; Asp, P <0.01); GOS was closely correlated to the EAA values (Glu, rs = 0.5737, P <0.001; Asp, rs = 0.5470, P <0.001). CONCLUSIONS: The EAA concentrations in CSF increase after acute head injury and remain higher for at least 1 week post injury in severely injured patients. The more severe the trauma, the more obvious the excitotoxicity induced by EAAs and the worse the outcome.

Acute Disease↗

PubMed2001

[Phosphorus sorption and desorption of agricultural soils under different land uses].

The potential of P loss from soils under different land uses in Taihu Lake watershed was evaluated by laboratory experiment. It was shown that although the P sorption capacity of paddy soils under oxidized conditions were little lower than that of dryland soils the risks of P loss from the former via runoff and leaching were lower than that from the latter, because the soil P levels of the former were much lower than that of the latter. For most paddy soils the P sorption capacity increased and the P release decreased under reduced conditions than that under oxidized conditions and this was attributed to the formation of amorphous Fe2+ hydroxides which have a greater surface area and more P sorption sites than well-crystallized Fe3+ oxides.

Adsorption↗

PubMed2001

[Effect of a new triclosan-containing mouth rinse on oral infection].

OBJECTIVE: To study the effect of a new Triclosan-containing mouthrinse--LIBO Anti-plaque mouth rinse on oral infection. METHODS: 1. Before and after the use of triclosan mouthrinse: the gingival data were checked and secorded; plaque sausples were collected, cultured in selective and non-selective media, bacteria were isolated, sounted, and compased. 2. With Streptococcus mutans and P. Gingivalis as experimental bacteria, triclosan and chlorhexidine (CHX) mouthrinses anti-bacterium substance, the minimum inhibitory concentrations (MICs) of the two rinses were compared. 3. Smooth plates with the film of Streptococcus mutans C were set in different mouthrinses and water. Observing the exfoliation of bacteria film from the plates in three agents. RESULTS: 1. Triclosan mouthrinse was effective to decrease the plaque index (PLI) and supragingival bleeding index (SBI). 2. The bacteria count obtained after use of triclosan mouthrinse was lower than that before using it. 3. The minimum inhibitory concentrations of triclosan mouthrinse against Streptococcus mutans C was much lower than that of chlorhexidine mouthrinse. 4. In triclosan mouthrinse, the bacterial films were most easily exfoliated from the plate. Triclosan mouthrinse has strongest anti-adhesion effect among the three tested agents. CONCLUSIONS: Triclosan mouthrinse has continuous disinfecting effect and help control the formation and adhesion of dental plaque.

Adult↗

PubMed2001

[Clinicopathological and molecular genetic analysis in Chinese typical hereditary nonpolyposis colorectal cancer pedigrees].

OBJECTIVE: To investigate the clinicopathological and molecular genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. METHODS: Four Chinese HNPCC pedigrees were studied using microdissection, microsatellite instability analysis, immunohistochemistry staining and direct DNA sequencing for hMSH2 and hMLH1 genes. RESULTS: All five tumor tissues from 4 probands showed high level of microsatellite instability at more than 2 loci(RER + phenotype). Three of 4 cases lost hMSH2 protein expression and one case showed no hMLH1 protein expression. Three pathological germline mutations (2 on hMSH2 and 1 on hMLH1) were identified. CONCLUSIONS: Chinese typical HNPCC kindreds showed relatively frequent germline mutations of mismatch repair genes. Microsatellite instability analysis and immunohistochemistry staining might be the effective screening methods before direct DNA sequencing for the detection of mismatch repair genes. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC kindreds.

Adult↗

PubMed2001

Clinicopathologic study of mucosa-associated lymphoid tissue lymphoma of the salivary gland.

OBJECTIVE: To study the histopathologic features and pathogenesis of mucosa-associated lymphoid tissue lymphoma (MALT-oma) of salivary glands. METHODS: Clinical data, paraffin-embedded sections, immunohistochemical slides (SP method) and electron microscopic features of surgical specimens of 32 cases of salivary gland MALT-oma were studied. RESULTS: The patients were 27 males and 5 females, with a mean age of 54.76 years. The lesions were located in the parotid area in 17 cases, and in the submandibular gland in the remaining 15 cases. Much of the MALT-oma was replaced by infiltration of a great amount of centrocyte-like cells (CCL) as background and occasional large cells (centroblast- or immunoblast-like). In MALT-omas "lymphoepithelial lesions" were present. Immunohistochemically, CD20 expression was found to be positive and CD45RO expression was negative in all MALT-omas. CONCLUSION: Most of the MALT-omas are low grade malignant tumors and have a "homing back" phenomenon. The cases were managed by surgery and chemotherapy. In a few MALT-omas which turned into high grade malignant tumors, the prognosis was poor. Acquired MALT may develop as a reaction to autoimmune disease and infection. Hyper-immune reaction and MALT hyperplasia under stimulation may result in myoepithelial sialadenitis and lead to MALT-oma of the salivary gland.

Adolescent↗

PubMed2001

Pathogen of root surface caries in the elderly.

OBJECTIVE: To study the pathogen of root surface caries in the elderly. METHODS: Plaque samples from the experimental group and the control group were collected. After culturing in selective and non-selective media, the different bacteria were isolated. The counts and the positive rates of total bacteria, porphyromonas group, pervotella group, streptococcus mutants group, actinomyces group and lactobacillus group were compared. RESULTS: The counts of total bacteria, streptococcus mutants, actinomyces and lactobacillus of the experimental group were higher than those of the control group. The positive rates of actinomyces and lactobacillus of the experimental group were significantly higher than those of the control group. CONCLUSION: Actinomyces and lactobacillus are the main related pathogens of root surface caries in the elderly.

Actinomyces↗

PubMed2001

Stable clonal expansion of the T-cell receptor V beta 6, V beta 17 and V beta 19 T cells in a cGVHD case using genescan analysis.

OBJECTIVE: To investigate the distribution and clonality of the T-cell receptor (TCR) V beta repertoire in chronic graft versus host disease (cGVHD). METHODS: The complementarity determining region 3 (CDR3) of the TCR beta gene with 24 variable regions was amplified in peripheral blood mononuclear cells drawn from one cGVHD patient after allogenic bone marrow transplantation (allo-BMT) 35, 39, 43 or 45 months respectively, using RT-PCR, to observe the expression of TCR V beta repertoire T cells. The PCR products were further analyzed by genescan to evaluate clonality of T cells. RESULTS: Fourteen or 16 TCR V beta subfamily T cells were detected in each sample of cGVHD case. Oligoclonal T cells were identified in TCR V beta 6, 16, 17, 19 and 21 subfamilies. The stable clonal T cells in all samples were identified in V beta 6, V beta 17 and V beta 21 subfamilies. CONCLUSION: Skewing distribution and stable clonal expansion of T cells can be found in cGVHD cases and it may be related to the initiation of cGVHD.

Adult↗