Biomedical subjects

H Su

Publications and source records attributed to H Su.

At least 37 records · Page 2Linked to original sources

PubMed2001

[Acidity and acid buffering capacity of aerosols during sand-dust storm weather in Beijing].

In the spring of 2000, there were 12 sand-dust storms in Beijing. 2 sand-dust storms were experienced in time and mass concentrations, elementary concentrations acidity and acidic buffering capacity of TSP(Total Suspended Particulate, < 100 microns) and PM10(Inhalable particulate, < 10 microns) were sampled and analyzed. Results showed that pollution level of aerosols was extremely high. However, the acidity of aerosols was relatively low and the aerosols had very strong acid buffering capacity for acidification. Therefore, the aerosols brought about by the sand-dust storms could avoid the occurrence of acidic precipitation to some extent.

Acids↗

PubMed2001

[Relationship among lymphatic metastasis, pericancerous lymphocytic reaction and dendritic cell infiltration in laryngeal carcinoma cells].

OBJECTIVE: To study the role and the clinical significance of dendritic cell infiltration against tumor cells in patients with laryngeal squamous cell carcinoma. METHODS: Immunohistochemical method using S-100 protein antibody was employed to detect dendritic cells (DC) on paraffin-embedded tissue sections from 23 patients with laryngeal squamous cell carcinomas. The relationships among the density of dendritic cell infiltration in laryngeal carcinomas and cervical lymphatic metastasis, pericancerous lymphocytic reaction and other clinicopathologic parameters were observed. RESULTS: The numbers of dendritic cells infiltrating among laryngeal carcinoma cells in patients with no cervical lymph metastasis was significantly larger than those with cervical lymphatic metastasis (t = 4.889, P < 0.01). Significant increase DC infiltration among laryngeal carcinoma cells was found in the group with intensively positive reaction of pericancerous lymphocyte than in the medium and weakly positive groups. The number of infiltrating dendritic cells in patients who had survived more than 5 years was significantly larger than those survived less than 5 years (t = 4.423, P < 0.01). The numbers of the infiltrating dendritic cells in patients with well-differentiated squamous cell carcinoma and poorly differentiated squamous cells carcinoma were 2.2 +/- 1.07 and 14.6 +/- 7.14 respectively, which were significantly different (q = 4.532, P < 0.05). CONCLUSION: The study showed that DC infiltration among laryngeal squamous carcinoma cells played an important role in the host immune reaction against tumor. It indicated that when the density of infiltrating DC is higher, the patients had less chance of cervical lymph metastasis and may have a longer survival time. There was a coordinative effect between DC infiltration in tumor cells and pericancerous lymphocyte reaction. Thus, the DC infiltration among laryngeal squamous cells could be used as an index of prognosis.

Aged↗

PubMed2001

[Differential expression analysis and cloning of murine thymic aged-related genes].

OBJECTIVE: Differential expression analysis and cloning of murine thymic aged-related genes. METHODS: Different expressions of thymic mRNAs from 1- and 10-month old mice were analyzed via DDRT-PCR and different expression sequence tags (ESTs) were obtained, following by identification with Northern Blotting, DNA sequencing, as well as screening of cDNA library. RESULTS: It was found that there would be a significant difference of gene expression in murine thymuses. Gene expression of some genes were exclusive in thymus from 1 or 10-month old mice, while some expressed different with age. 108 differential display cDNA fragments were recovered, among which 31 were positive for hybridization by Northern blot. After sequenced, 14 ESTs were found to share high homology to known genes, whereas remaining 17 were novel. A murine thymic cDNA library was screened by using one cDNA fragment that expressed with higher level in total RNA of 1-month old murine thymic tissues than 10-month old. Finally, one 1,470 bp fragment was cloned and showed a 99% of homology to murine transketolase. CONCLUSION: Expression of murine thymic genes has displayed a marked difference with age. These genes might be participated in thymic atrophy.

Aging↗

PubMed2000

Adeno-associated viral vector-mediated vascular endothelial growth factor gene transfer induces neovascular formation in ischemic heart.

Vascular endothelial growth factor (VEGF) plays important roles in physiological and pathological angiogenesis. Recent studies have demonstrated that direct injection of VEGF protein, plasmid DNA, or an adenoviral vector encoding the VEGF gene into ischemic myocardium or limb can induce collateral blood vessel formation and improve perfusion of the ischemic areas. However, these approaches have limitations ranging from a short-lasting effect to angioma formation. In this study, we investigated the feasibility of using adeno-associated viral (AAV) vectors to deliver VEGF genes to mouse myocardium. A cytomegalovirus promoter was used to drive genes for a human VEGF isoform, VEGF(165), and LacZ. A mouse myocardial ischemic model was generated by ligation of the anterior descending coronary artery. Approximately 10(11) copies of the AAV-VEGF vector mixed with 10(10) copies of AAV-LacZ were injected to one site of normal myocardium and a total of 10(11) copies of AAV-VEGF were injected to multiple sites of myocardium around the ischemic region. LacZ gene expression was observed up to 3 months after the vector inoculation. After AAV-VEGF inoculation, neoangiogenesis was observed in the ischemic heart model but not in normal heart tissue. An inflammatory-cell infiltration was not observed in the AAV-VEGF- and AAV-LacZ-inoculated hearts, and angioma-like structure was not observed. These results indicated that injection of the AAV vector directly to myocardium could mediate efficient gene transfer and transgene expression and that VEGF gene delivered by AAV vector can induce angiogenesis in ischemic myocardium.

Animals↗

PubMed2000

Mutation of arginine 44 of GAT-1, a (Na(+) + Cl(-))-coupled gamma-aminobutyric acid transporter from rat brain, impairs net flux but not exchange.

The gamma-aminobutyric acid (GABA) transporter GAT-1 is a prototype of a large family of neurotransmitter transporters that includes those of dopamine and serotonin. GAT-1 maintains low synaptic concentrations of neurotransmitter by coupling GABA uptake to the fluxes of sodium and chloride. Here we identify a stretch of four amino acid residues predicted to lie in the juxtamembrane region prior to transmembrane domain 1 in the cytoplasmic amino-terminal tail of GAT-1, which is critical for its function. Two residues, arginine 44 and tryptophan 47, are fully conserved within the transporter family, and their deletion abolishes GABA transport in the HeLa cell expression system used. Tryptophan 47 can be replaced only by aromatic residues without loss of activity. Arginine 44 is essential for activity. Only when it is replaced by lysine, low activity levels (around 15% of those of the wild type) are observed. Using a reconstitution assay, we show that mutants in which this residue is replaced by lysine or histidine exhibit sodium- and chloride-dependent GABA exchange similar to the wild type. This indicates that these mutants are selectively impaired in the reorientation of the unloaded transporter, a step in the translocation cycle by which net flux and exchange differ. The high degree of conservation in the consensus sequence RXXW suggests that this region may influence the reorientation step in related transporters as well.

Amino Acid Substitution↗

PubMed2000

BAC contig from a 3-cM region of mouse chromosome 11 surrounding Brca1.

Even with the completion of a draft version of the human genome sequence only a fraction of the genes identified from this sequence have known functions. Chromosomal engineering in mouse cells, in concert with gene replacement assays to prove the functional significance of a given genomic region or gene, represents a rapid and productive means for understanding the role of a given set of genes. Both techniques rely heavily on detailed maps of chromosomal regions, initially to understand the scope of the regions being modified and finally to provide the cloned resources necessary to allow both finished sequencing and large insert complementation. This report describes the creation of a BAC clone contig on mouse chromosome 11 in a region showing conservation of synteny with sequences on human chromosome 17. We have created a detailed map of an approximately 3-cM region containing at least 33 genes through the use of multiple BAC mapping strategies, including chromosome walking and multiplex oligonucleotide hybridization and gap filling. The region described is one of the targets of a large effort to create a series of mice with regional deletions on mouse chromosome 11 (33-80 cM) that can subsequently be subjected to further mutagenesis.

Animals↗

PubMed2000

Overexpression of murine fizzy-related (fzr) increases natural killer cell-mediated cell death and suppresses tumor growth.

Fizzy-related (fzr) is a recently identified 7WD domain family member implicated in cell cycle regulation of Drosophila and yeast. In this study, the murine homologue of fzr was isolated by suppression subtractive hybridization as a gene with decreased expression during malignant progression of a murine B-lymphoma cell line. Retroviral overexpression of fzr in B-lymphoma cells reduced tumor formation. Those tumors that did arise had diminished or extinguished retroviral Fzr. Surprisingly, fzr overexpression dramatically increased B-lymphoma cell susceptibility to natural killer cell (NK) cytotoxicity, a host-resistant mechanism for tumor formation in this model system. These findings implicate fzr as a new category of genes suppressing B-cell tumorigenesis and suggest a novel role for fzr in the target cell interaction with NK cells.

Animals↗

PubMed2000

Zinc-enriched boutons in rat spinal cord.

The rat spinal cord reveals a complex pattern of zinc-enriched (ZEN) boutons. As a result of in vivo exposure to selenide ions, nanosized clusters of zinc selenide are created in places where zinc ions are present, including the zinc-containing synaptic vesicles of ZEN boutons. The clusters can be silver enhanced by autometallographic (AMG) development. A description of the ZEN bouton patterns is presented and discussed. The distribution of ZEN boutons could indicate that these terminal systems have a differentiated influence on sensory and motor systems.

Animals↗

PubMed2000

The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages.

Mycobacterium tuberculosis is an important pathogen of mammals that relies on 2-hydroxyphenyloxazoline-containing siderophore molecules called mycobactins for the acquisition of iron in the restrictive environment of the mammalian macrophage. These compounds have been proposed to be biosynthesized through the action of a cluster of genes that include both nonribosomal peptide synthase and polyketide synthase components. One of these genes encodes a protein, MbtB, that putatively couples activated salicylic acid with serine or threonine and then cyclizes this precursor to the phenyloxazoline ring system. We have used gene replacement through homologous recombination to delete the mbtB gene and replace this with a hygromycin-resistance cassette in the virulent strain of M. tuberculosis H37Rv. The resulting mutant is restricted for growth in iron-limited media but grows normally in iron-replete media. Analysis of siderophore production by this organism revealed that the biosynthesis of all salicylate-derived siderophores was interrupted. The mutant was found to be impaired for growth in macrophage-like THP-1 cells, suggesting that siderophore production is required for virulence of M. tuberculosis. These results provide conclusive evidence linking this genetic locus to siderophore production.

Bacterial Proteins↗

PubMed2000

Adeno-associated viral-mediated gene transfer to hepatoma: thymidine kinase/interleukin 2 is more effective in tumor killing in non-ganciclovir (GCV)-treated than in GCV-treated animals.

Interleukin 2 (IL-2) enhancement of herpes simplex virus-thymidine kinase (HSV-TK)/ganciclovir (GCV)-induced tumor killing was studied by cloning the human interleukin 2 gene into an HSV-TK-bearing adeno-associated viral (AAV) vector (TK/IL-2). The mouse hepatocellular carcinoma cell line Hepa 1-6 was used as a model in this study. We found that TK/IL-2-transduced Hepa 1-6 cells were more susceptible to ganciclovir treatment than tumor cells transduced with only TK in both nude mice and immunocompetent C57L/J mice. TK/IL-2-transduced tumors also showed shrinkage without GCV treatment. The tumor-killing effect of AAV-mediated TK/IL-2 gene transfer was further studied by inoculating animals with TK/IL-2- or TK-transduced tumor cells mixed with unmodified cells with or without GCV treatment. Although tumor growth in each group was inhibited, the best result was obtained from the TK/IL-2-transduced group without GCV treatment. In this group, 10% of the transduced tumor cells could eradicate the whole tumor in 50% of the animals tested as well as provide long-term protection against tumor cell rechallenge. When this group was treated with GCV, the antitumor effect of TK/IL-2 was reduced. We attribute this to the early ablation of transgene-bearing tumor cells by GCV treatment, which thus reduces the duration of IL-2 expression. We conclude that (i) TK/IL-2 plus GCV treatment generates a stronger tumor-killing effect than HSV-TK plus GCV and (ii) tumor killing of TK/IL-2 is more effective in non-GCV-treated animals than in GCV-treated animals.

Animals↗

PubMed2000

Identifiability and interval identifiability of mammillary and catenary compartmental models with some known rate constants.

The identifiability problem is addressed for n-compartment linear mammillary and catenary models, for the common case of input and output in the first compartment and prior information about one or more model rate constants. We first define the concept of independent constraints and show that n-compartment linear mammillary or catenary models are uniquely identifiable under n-1 independent constraints. Closed-form algorithms for bounding the constrained parameter space are then developed algebraically, and their validity is confirmed using an independent approach, namely joint estimation of the parameters of all uniquely identifiable submodels of the original multicompartmental model. For the noise-free (deterministic) case, the major effects of additional parameter knowledge are to narrow the bounds of rate constants that remain unidentifiable, as well as to possibly render others identifiable. When noisy data are considered, the means of the bounds of rate constants that remain unidentifiable are also narrowed, but the variances of some of these bound estimates increase. This unexpected result was verified by Monte Carlo simulation of several different models, using both normally and lognormally distributed data assumptions. Extensions and some consequences of this analysis useful for model discrimination and experiment design applications are also noted.

Algorithms↗

PubMed2000

Nested chromosomal deletions induced with retroviral vectors in mice.

Chromosomal deletions, especially nested deletions, are major genetic tools in diploid organisms that facilitate the functional analysis of large chromosomal regions and allow the rapid localization of mutations to specific genetic intervals. In mice, well-characterized overlapping deletions are only available at a few chromosomal loci, partly due to drawbacks of existing methods. Here we exploit the random integration of a retrovirus to generate high-resolution sets of nested deletions around defined loci in embryonic stem (ES) cells, with sizes extending from a few kilobases to several megabases. This approach expands the application of Cre-loxP-based chromosome engineering because it not only allows the construction of hundreds of overlapping deletions, but also provides molecular entry points to regions based on the retroviral tags. Our approach can be extended to any region of the mouse genome.

Animals↗

PubMed2000

Isolation and expression in Escherichia coli of cslA and cslB, genes coding for the chondroitin sulfate-degrading enzymes chondroitinase AC and chondroitinase B, respectively, from Flavobacterium heparinum.

In medium supplemented with chondroitin sulfate, Flavobacterium heparinum synthesizes and exports two chondroitinases, chondroitinase AC (chondroitin AC lyase; EC 4.2.2.5) and chondroitinase B (chondroitin B lyase; no EC number), into its periplasmic space. Chondroitinase AC preferentially depolymerizes chondroitin sulfates A and C, whereas chondroitinase B degrades only dermatan sulfate (chondroitin sulfate B). The genes coding for both enzymes were isolated from F. heparinum and designated cslA (chondroitinase AC) and cslB (chondroitinase B). They were found to be separated by 5.5 kb on the chromosome of F. heparinum, transcribed in the same orientation, but not linked to any of the heparinase genes. In addition, the synthesis of both enzymes appeared to be coregulated. The cslA and cslB DNA sequences revealed open reading frames of 2,103 and 1,521 bp coding for peptides of 700 and 506 amino acid residues, respectively. Chondroitinase AC has a signal sequence of 22 residues, while chondroitinase B is composed of 25 residues. The mature forms of chondroitinases AC and B are comprised of 678 and 481 amino acid residues and have calculated molecular masses of 77,169 and 53,563 Da, respectively. Truncated cslA and cslB genes have been used to produce active, mature chondroitinases in the cytoplasm of Escherichia coli. Partially purified recombinant chondroitinases AC and B exhibit specific activities similar to those of chondroitinases AC and B from F. heparinum.

Blotting, Southern↗

PubMed2000

Subclinical chlamydial infection of the female mouse genital tract generates a potent protective immune response: implications for development of live attenuated chlamydial vaccine strains.

Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed. CD4(+) T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection. Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa. Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C. trachomatis vaccine. Attenuated strains of C. trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection. We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection. Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log(10)) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae. Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice. Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally. These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response. They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs.

Animals↗

PubMed2000

Immunity to murine Chlamydia trachomatis genital tract reinfection involves B cells and CD4(+) T cells but not CD8(+) T cells.

CD4(+) T-helper type 1 (Th1) responses are essential for the resolution of a primary Chlamydia trachomatis genital tract infection; however, elements of the immune response that function in resistance to reinfection are poorly understood. Defining the mechanisms of immune resistance to reinfection is important because the elements of protective adaptive immunity are distinguished by immunological memory and high-affinity antigen recognition, both of which are crucial to the development of efficacious vaccines. Using in vivo antibody depletion of CD4(+) and CD8(+) T cells prior to secondary intravaginal challenge, we identified lymphocyte populations that functioned in resistance to secondary chlamydial infection of the genital tract. Depletion of either CD4(+) or CD8(+) T cells in immune wild-type C57BL/6 mice had a limited effect on resistance to reinfection. However, depletion of CD4(+) T cells, but not CD8(+) T cells, in immune B-cell-deficient mice profoundly altered the course of secondary infection. CD4-depleted B-cell-deficient mice were unable to resolve a secondary infection, shed high levels of infectious chlamydiae, and did not resolve the infection until 3 to 4 weeks following the discontinuation of anti-CD4 treatment. These findings substantiated a predominant role for CD4(+) T cells in host resistance to chlamydial reinfection of the female genital tract and demonstrated that CD8(+) T cells are unnecessary for adaptive immune resistance. More importantly, however, this study establishes a previously unrecognized but very significant role for B cells in resistance to chlamydial reinfection and suggests that B cells and CD4(+) T cells may function synergistically in providing immunity in this model of chlamydial infection. Whether CD4(+) T cells and B cells function independently or dependently is unknown, but definition of those mechanisms is fundamental to understanding optimum protective immunity and to the development of highly efficacious immunotherapies against chlamydial urogenital infections.

Animals↗

PubMed2000

Orphan receptor COUP-TF is required for induction of retinoic acid receptor beta, growth inhibition, and apoptosis by retinoic acid in cancer cells.

Retinoic acid receptor beta (RARbeta) plays a critical role in mediating the anticancer effects of retinoids. Expression of RARbeta is highly induced by retinoic acid (RA) through a RA response element (betaRARE) that is activated by heterodimers of RARs and retinoid X receptors (RXRs). However, RARbeta induction is often lost in cancer cells despite expression of RARs and RXRs. In this study, we provide evidence that orphan receptor COUP-TF is required for induction of RARbeta expression, growth inhibition, and apoptosis by RA in cancer cells. Expression of COUP-TF correlates with RARbeta induction in a variety of cancer cell lines. In addition, stable expression of COUP-TF in COUP-TF-negative cancer cells restores induction of RARbeta expression, growth inhibition, and apoptosis by RA, whereas inhibition of COUP-TF by expression of COUP-TF antisense RNA represses the RA effects. In a transient transfection assay, COUP-TF strongly induced transcriptional activity of the RARbeta promoter in a RA- and RARalpha-dependent manner. By mutation analysis, we demonstrate that the effect of COUP-TF requires its binding to a DR-8 element present in the RARbeta promoter. The binding of COUP-TF to the DR-8 element synergistically increases the RA-dependent RARalpha transactivation function by enhancing the interaction of RARalpha with its coactivator CREB binding protein. These results demonstrate that COUP-TF, by serving as an accessory protein for RARalpha to induce RARbeta expression, plays a critical role in regulating the anticancer activities of retinoids.

Animals↗

PubMed2000

[Prevalence of prostatic hyperplasia and its relative factors in six cities of China in 1997].

OBJECTIVE: To study crude prevalence and distribution of the elderly prostatic hyperplasia. METHODS: Three thousand three hundred and sixty-one elderly aged 60 years and above in the urban and rural areas of Beijing, Shanghai, Guangzhou, Chengdu, Xi'an and Shenyang were investigated, using clustered random sampling methods. RESULTS: The crude prevalence of prostatic hyperplasia was found to be 43.68% with an increase with ageing (P < 0.01). The crude prevalence rates of prostatic hyperplasia among the elderly of 60-, 65-, 70-, 75-, 80-, 85- years old were 34.48%, 40.27%, 46.77%, 51.44%, 57.32% and 60.19% respectively (P < 0.01). Rates in the urban and rural areas were 46.79%and 39.64% respectively. The crude prevalence of urban areas was higher than that of rural areas (P < 0.01) and was found higher in Beijing (63.28%) and Guangzhou (54.28%), (P < 0.01). The crude rates prevalence of managers (54.88%), teachers and business men (55.17%) were in general higher than the prevalence of the workers (41.29%) and peasant (37.26%). Logistic regression analysis showed that the crude prevalence was related to ageing, profession and residential areas (P respective < 0.01). CONCLUSION: The prevalence of prostatic hyperplasia was higher in the elderly and became a common disease of the male elderly in China. Prevention and treatment of prostatic hyperplasia in the elderly should be strengthened.

Age Distribution↗

PubMed2000

[Effect of macrophage nitric oxide on the ultrafiltration failure of long-term peritoneal dialysis].

OBJECTIVE: The regulation of macrophage nitric oxide on peritoneal lymphatic stomata was studied for revealing the mechanism of ultrafiltration failure during long-term peritoneal dialysis. METHODS: (1) The model of peritoneal dialysis was created by using peritoneal dialysate; (2) Dynamic measurements of nitric oxide (NO) were made during peritoneal dialysis and its cessation; (3) The pathological change of the peritoneal mesothelium in different dialysis time was observed by scanning electron microscope (SEM); (4) Dynamic changes of the peritoneal lymphatic stomata were studied during this experiment by using a computer image processing system attached to SEM. RESULTS: Numerous macrophages went into the peritoneal cavity through the lymphatic stomata to form a lot of milky spots during peritoneal dialysis. A great quantity of NO produced by macrophages damaging mesothelial cells and increasing numbers and density of lymphatic stomata. After 40 days of peritoneal dialysis, the diameters of the lymphatic stomata were significantly increased in Bieffe group (P < 0.05). During cessation of peritoneal dialysis, few macrophage milky spots were observed and NO quantity was gradually decreased. Then the mesothelium damage began to repair and the peritoneal lymphatic stomata tended to become normal. CONCLUSIONS: Our data demonstrate that a great quantity of NO produced by macrophages would damage peritoneal mesothelium and relax lymphatic stomata which enhance lymphatic reabsorption from the peritoneal cavity so as to make ultrafiltration failure on long-term peritoneal dialysis.

Absorption↗