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Biomedical subjects

H Su

Publications and source records attributed to H Su.

At least 73 records · Page 4Linked to original sources
PubMed1998

Vaccination against chlamydial genital tract infection after immunization with dendritic cells pulsed ex vivo with nonviable Chlamydiae.

Chlamydia trachomatis, an obligate intracellular bacterial pathogen of mucosal surfaces, is a major cause of preventable blindness and sexually transmitted diseases for which vaccines are badly needed. Despite considerable effort, antichlamydial vaccines have proven to be elusive using conventional immunization strategies. We report the use of murine bone marrow-derived dendritic cells (DC) pulsed ex vivo with killed chlamydiae as a novel approach to vaccination against chlamydial infection. Our results show that DC efficiently phagocytose chlamydiae, secrete IL-12 p40, and present chlamydial antigen(s) to infection sensitized CD4(+) T cells. Mice immunized intravenously with chlamydial-pulsed DC produce protective immunity against chlamydial infection of the female genital tract equal to that obtained after infection with live organisms. Immunized mice shed approximately 3 logs fewer infectious chlamydiae and are protected from genital tract inflammatory and obstructive disease. Protective immunity is correlated with a chlamydial-specific Th1-biased response that closely mimics the immune response produced after chlamydial infection. Thus, ex vivo antigen-pulsed DC represent a powerful tool for the study of protective immunity to chlamydial mucosal infection and for the identification of chlamydial protective antigens through reconstitution experiments. Moreover, these findings might impact the design of vaccine strategies against other medically important sexually transmitted diseases for which vaccines are sought but which have proven difficult to develop.

Adoptive Transfer↗
PubMed1998

Sulfated polysaccharides and a synthetic sulfated polymer are potent inhibitors of Chlamydia trachomatis infectivity in vitro but lack protective efficacy in an in vivo murine model of chlamydial genital tract infection.

Heparin, dextran sulfate, pentosan polysulfate, and a sulfated synthetic copolymer of acrylic acid and vinyl alcohol were shown to be potent inhibitors of Chlamydia trachomatis infectivity for cultured human epithelial cells. Despite their potent antichlamydial activity in vitro, neither heparin nor dextran sulfate was effective in inhibiting the infectivity of C. trachomatis in a murine model of chlamydial infection of the female genital tract.

Animals↗
PubMed1998

Growth suppression by an E2F-binding-defective retinoblastoma protein (RB): contribution from the RB C pocket.

Growth suppression by the retinoblastoma protein (RB) is dependent on its ability to form complexes with transcription regulators. At least three distinct protein-binding activities have been identified in RB: the large A/B pocket binds E2F, the A/B pocket binds the LXCXE peptide motif, and the C pocket binds the nuclear c-Abl tyrosine kinase. Substitution of Trp for Arg 661 in the B region of RB (mutant 661) inactivates both E2F and LXCXE binding. The tumor suppression function of mutant 661 is not abolished, because this allele predisposes its carriers to retinoblastoma development with a low penetrance. In cell-based assays, 661 is shown to inhibit G1/S progression. This low-penetrance mutant also induces terminal growth arrest with reduced but detectable activity. We have constructed mutations that disrupt C pocket activity. When overproduced, the RB C-terminal fragment did not induce terminal growth arrest but could inhibit G1/S progression, and this activity was abolished by the C-pocket mutations. In full-length RB, the C-pocket mutations reduced but did not abolish RB function. Interestingly, combination of the C-pocket and 661 mutations completely abolished RB's ability to cause an increase in the percentage of cells in G1 and to induce terminal growth arrest. These results suggest that the A/B or C region can induce a prolongation of G1 through mechanisms that are independent of each other. In contrast, long-term growth arrest requires combined activities from both regions of RB. In addition, E2F and LXCXE binding are not the only mechanisms through which RB inhibits cell growth. The C pocket also contributes to RB-mediated growth suppression.

Binding Sites↗
PubMed1998

[Relationship between clinical manifestation and pathology in pediatric renal diseases].

To elevate the clinical diagnosis and pathological compatibility of pediatric kidney diseases. Pathological changes from 101 cases of pediatric renal diseases were studied, covering 13 diseases entities, including glomerulo-nephritis, simple nephrotic syndrome, nephritic nephrotic syndrome etc. The technique of tru-cut biopsy under the guidance of B ultrasonogram was used in renal biopsy. The renal puncture biopsy was 100% satisfactory. Pathological changes involved 12 pathological types. MsPGN were the most commonly seen (39.6%), followed by MPGN and ICPGN (12.87% and 10.89%) respectively. It was found that children with similar clinical manifestation may possess different pathological changes, while the same pathological entity may present multiple clinical manifestation. The results suggest that renal biopsy pathological diagnosis is important in the diagnosis, treatment and prediction of prognosis in pediatric renal disease.

Adolescent↗
PubMed1998

[The value of color Doppler ultrasonography in diagnosing aneurysm].

Using Doppler ultrasound, we detected 59 patients with aneurysm, 54 cases were confirmed by angiography or operation or both. Among them, 33 cases (63%) showed true aneurysm, 18 cases (33%) pseudoaneurysm, and 2 cases (4%) superficial congenital arterio-venous aneurysm. Eight cases were associated with dissected stripping. One case was falsely diagnosed by ultrasonography. The diagnostic accuracy was 98%. The results suggest that color Doppler ultrasonography is useful in detecting aneurysm.

Adult↗
PubMed1998

[Effects of tetramethylpyrazine and radix salviae miltiorrhizae on collagen synthesis and proliferation of cardiac fibroblasts].

OBJECTIVE: To explore the effects of Tetramethylpyrazine (TMP) and Radix Salviae Miltiorrhizae (RSM) in collagen synthesis and proliferation of cardiac fibroblasts. METHODS: Using collagenase and trypsase digested rat cardiac tissue assay to isolate cardiac fibroblasts (Fbs). Different dosage of TMP, RSM and norepinephrine (NE) were used to study their effects on the collagen synthesis and proliferation of cultured cardiac Fbs. RESULTS: Compared with the control group, moderate or high dosage TMP and RSM could significantly inhibit the collagen synthesis and the proliferation of cultured cardiac Fbs. Moreover, low-dose TMP(50 mg/L) and low-dose RSM(3 g/L) could antagonize the collagen synthesis and the proliferation of cultured cardiac FB stimulated by NE (500 micrograms/L). CONCLUSION: Both TMP and RSM could inhibit these processes. The mechanisms of these effect might be correlated to their Ca++ antagonistic action.

Animals↗
PubMed1998

[The estrogenic activities of 2-[3-estrone-N-ethyl-piperazine-methyl]tetracycline(XW630)--a new compound with anti-osteoporosis activity].

2-[3-Estrone-N-ethyl-piperazine-methyl] tetracycline (XW630) showing anti-osteoporosis activity is a new compound with piperazine-tetracycline in the steroid structure of estrone. The affinity of XW630 with uterine estrogen receptor and its estrogenic activity were studied in this paper. The relative affinities of estrone, estradiol and XW630 with estrogen receptor (ER) of the uterine myoma tissues were found to be 0.325, 1.000 and 0.011, respectively, by the competitive assay. The estrogenic activity index of estrone, estradiol and XW630 were shown to be 9.70, 10.30 and 6.90, respectively, by the uterine weight assay using immature mice. These indexes indicate that: the estrogenic activity of XW630 is about 1/1960 that of estrone and 1/7742 that of estradiol. The vaginal smear assay of oophorectomized mice also showed that the estrogenic activity of XW630 is less than that of estrone and estradiol.

Animals↗
PubMed1997

Tissue-specific expression of herpes simplex virus thymidine kinase gene delivered by adeno-associated virus inhibits the growth of human hepatocellular carcinoma in athymic mice.

About 70% of hepatocellular carcinomas are known to express alpha-fetoprotein, which is normally expressed in fetal but not in adult livers. To induce herpes simplex virus-thymidine kinase expression in these cancer cells, we constructed an adeno-associated viral vector containing the HSV-TK gene under the control of the alpha-fetoprotein enhancer and albumin promoter. We previously demonstrated in vitro that although this vector can transduce a variety of human cells, only transduced AFP and albumin-expressing hepatocellular carcinoma cell lines were sensitive to killing by ganciclovir (GCV). In the present study, we explored the effect of this vector on hepatocellular carcinoma cells in vivo. Subcutaneous tumors generated in nude mice by implanting hepatocellular carcinoma cells previously transduced with this vector shrank dramatically after treatment with GCV. Bystander effect was also observed on the tumors generated by mixing transduced and untransduced cells. To test whether the tumor cells can be transduced by the virus in vivo, we injected the recombinant adeno-associated virus into tumors generated by untransduced hepatocarcinoma cell line. Tumor growth were retarded after treatment with GCV. These experiments demonstrate the feasibility of in vivo transduction of tumor cell with rAAV.

Animals↗
PubMed1997

Novel high-performance liquid chromatographic assay using fluorescence detection for the quantitation of plasma gamma-methylene-10-deazaaminopterin and its major metabolite, 7-hydroxy-gamma-methylene-10-deazaaminopterin, in patients with solid cancers in a phase I trial.

Gamma-methylene-10-deazaaminopterin (MDAM), a unique dihydrofolate reductase inhibitor, has demonstrated antitumor activity against a broad spectrum of human solid tumors in preclinical studies. A novel reversed-phase, ion-pair high-performance liquid chromatography (HPLC) assay that uses fluorescence detection has been developed to quantitate levels of MDAM and its major metabolite, 7-hydroxy-gamma-methylene-10-deazaaminopterin (7-OH-MDAM), in human plasma. The recovery of MDAM and 7-OH-MDAM from plasma was >97% by a simple one-step deproteinization process using tetrabutylammonium bromide (TBABr) and methanol. MDAM and 7-OH-MDAM remained stable in plasma over a 28-day test period at ambient temperatures, and neither compound was light-sensitive. The limit of quantitation was 0.005 microM for both MDAM and 7-OH-MDAM. This assay has been found to be simple, sensitive and reproducible in determining plasma concentrations of MDAM and 7-OH-MDAM in patients with solid cancers in a phase I trial.

Aminopterin↗
PubMed1997

Cytogenetic and molecular studies of a familial paracentric inversion of Y chromosome present in a patient with ambiguous genitalia.

Here we describe the first reported case of a patient with a familial paracentric inversion in the long arm of the Y chromosome and ambiguous genitalia. FISH analyses with Y chromosome YACs demonstrated that the inversion breakpoints of the patients and the father's Ys appear to be the same and lie within interval 5B of the Y chromosome. PCR and sequence analysis indicated that our patient carries a normal SRY gene. For an additional comparison of the patient's inv(Y) with the father, two other Y chromosome sequences were examined. Molecular studies of this familial inverted Y chromosome showed no differences in the ZFY and TSPY genes between the father and the patient suggesting that the short arm of our patient's inv(Y) is identical to that of the patient's father. Southern analysis using a probe of the DAX-1 gene indicated that a single copy of DSS (dosage sensitive sex reversal) locus was present in the patient. Our results suggest that the abnormal sexual development in our patient is likely attributable to (an)other mechanism(s) than mutation in the SRY gene and dosage alteration of the DAX-1 gene.

Chromosome Inversion↗
PubMed1997

Antisense mapping DOR-1 in mice: further support for delta receptor subtypes.

In contrast to the pharmacological studies implicating delta-opioid receptor subtypes, cloning studies have identified only a single cDNA encoding a delta receptor, DOR-1. Antisense studies have established the importance of DOR-1 in delta analgesia in mice. Antisense mapping extends this approach to include oligodeoxynucleotides which are targeted against each of the exons of the gene. Five different antisense oligodeoxynucleotides based upon the three DOR-1 exons all block both spinal and supraspinal analgesic actions of the delta2 ligand [D-Ala2,Glu4]deltorphin, consistent with the suggestion that DOR-1 encodes the delta2 receptor. At the spinal level, [D-Pen2,D-Pen5]enkephalin (DPDPE) acts also acts through delta2 receptors and all the antisense probes block spinal DPDPE analgesia. However, supraspinally only the two antisense probes targeting exon 3 block DPDPE analgesia. The remaining three antisense probes based upon exons 1 and 2 are inactive. Thus, the delta receptors responsible for spinal and supraspinal DPDPE analgesia can be discriminated at the molecular level by antisense mapping.

Analgesia↗
PubMed1997

Specific mutation near the primary donor in photosystem I from Chlamydomonas reinhardtii alters the trapping time and spectroscopic properties of P700.

Time-resolved absorption and fluorescence spectroscopy were used to investigate the energy and electron transfer processes in the detergent-isolated photosystem I core particles from the site-directed mutant of Chlamydomonas reinhardtii with the histidine-656 of PsaB replaced by asparagine [HN(B656) mutation]. The specific mutation near the primary donor molecule results in a 40 mV increase in the P700/P700+ midpoint potential [Webber, A. N., Su Hui, Bingham, S. E., Kass, H., Krabben, L., Kuhn, M., Jordan, R., Schlodder, E., & Lubitz, W. (1996) Biochemistry 35, 12857-12863]. There is no indication that the HN(B656) mutation affects the spectral distribution of the antenna pigments. However, the lifetime of the trapping process measured independently by transient absorption and fluorescence spectroscopy in the mutant PSI core antenna is increased by a factor of approximately 2 (approximately 65 ps compared to approximately 30 ps in the wild-type PSI). This implies that the trapping process in the PSI antenna is limited by the process where the primary donor molecule directly participates. The HN(B656) mutation results in the appearance of a new bleaching band at 670 nm in the spectrum which is due to formation of P700+ upon photooxidation. The difference spectrum of the photoreduction of the possible primary acceptor, A0 in the mutant PSI is very similar to wild type, indicating that it is unaffected by the HN(B656) mutation. Possible mechanisms for slowing of the trapping process and the appearance of a new band in the P700 - P700+ difference spectrum of the HN(B656) PSI are discussed.

Animals↗
PubMed1997

The cardiac troponin C isoform and the length dependence of Ca2+ sensitivity of tension in myocardium.

The Ca2+ sensitivity of tension in cardiac muscle is length dependent, such that the sensitivity is diminished with decreasing sarcomere length below 2.4 microm. This length dependence of Ca2+ sensitivity of tension also forms the basis for the Frank-Starling mechanism in the heart. The fast-twitch skeletal muscle has a much lower length dependence of Ca2+ sensitivity. In a recent study of skinned cardiotrabeculae, we indicated that the exchange of endogenous cardiac troponin C (TnC) for skeletal troponin C also resulted in a major reduction in the length dependence to the level of skeletal muscle. These findings suggested that cardiac troponin C has a key role in the length-sensing mechanism. The present investigation supports this conclusion and delineates the specific domain in cardiac TnC responsible for the length effect. Chimeras splicing either 41, 61, or 96 N-terminal cardiac amino acids with the remaining skeletal residues have indicated that while Ca2+ binding in all three constructs is similar to that in wild type cardiac TnC, the functional responsiveness of the 96-cardiac residue construct is improved over the other two. This 96-cardiac residue construct yielded a tension response indistinguishable from that of wild-type cardiac TnC. A tryptophan variant of the chimera indicated fluorescence characteristics indistinguishable from cardiac troponin C. The findings provide further support for the idea that cardiac troponin C in situ is modified in response to sarcomere length change and thereby participates in the Frank-Starling mechanism. Moreover, the study indicates that the tropinin C length-sensing attribute originates within the N-terminal domain constituted by these 96 residues.

Animals↗
PubMed1997

Acoustic waves and the real-time study of biochemical macromolecules at the liquid/solid interface.

The adsorption of the proteins, bovine serum albumin, fibrinogen, avidin and neutravidin (non-glycosylated form of avidin) to a variety of surfaces imposed on thickness shear mode sensors in examined in a flow-injection analysis format. In all cases, adsorption of these moieties was essentially irreversible, although the magnitude of adsorption was dependent on surface free energy and functional group chemistry. Also described is the direct, real-time detection of the binding of peptides to HIV-1 TAR RNA bound on a thickness-shear mode (TSM) sensor surface. The results clearly indicate that responses are discriminatory for two different peptides. In order to provide a theoretical backcloth for the experimental measurements, a new model for the operation of the TSM in liquids is presented.

Acoustics↗
PubMed1997

Chlamydia trachomatis genital tract infection of antibody-deficient gene knockout mice.

The importance of antibody-mediated immunity in primary and secondary Chlamydia trachomatis genital tract infections was examined by using a definitive model of B-cell deficiency, the microMT/microMT gene knockout mouse. Vaginally infected B-cell-deficient microMT/microMT mice developed a self-limiting primary infection that was indistinguishable from infection of control C57BL/6 mice. Sera and vaginal secretions from infected mice were analyzed for anti-Chlamydia antibodies. C57BL/6 mice produced high-titered serum anti-Chlamydia immunoglobulin G2a (IgG2a), IgG2b, and IgA antibodies, and vaginal washes contained predominately anti-Chlamydia IgA. Serum and vaginal washes from infected B-cell-deficient mice were negative for anti-Chlamydia antibody. T-cell proliferation and delayed-type hypersensitivity assays were used as measures of Chlamydia-specific cell-mediated immunity and were found to be comparable for C57BL/6 and B-cell-deficient mice. Seventy days following primary infection, mice were rechallenged to assess acquired immunity. B-cell-deficient mice which lack anti-Chlamydia antibodies were more susceptible to reinfection than immunocompetent C57BL/6 mice. However, acquired immune resistance was evident in both strains of mice and characterized by decreased shedding of chlamydiae and an infection of shorter duration. Thus, this study demonstrates that cell-mediated immune responses alone were capable of resolving chlamydial infection; however, in the absence of specific antibody, mice were more susceptible to reinfection. Therefore, these data suggest that both humoral and cell-mediated immune responses were important mediators of immune protection in this model, though cell-mediated immune responses appear to play a more dominant role.

Animals↗
PubMed1997

[Quantitative change of glucagon and insulin immunoreactivities in the pancreas of fasting rats].

In this study, the glucagon and insulin immunoreactivities in the fasting rat pancreas were quantitated by image analysis. The results showed that the glucagon immunoreactivity significantly decreased in fasting rats and that of insulin increased, as compared with that in normal rats. The glucagon immunoreactivity significantly increased after intravenous injection of glucose but no marked difference was found in insulin. These results suggest that the A cells of pancreas may be directly stimulated by nutrients, and the B cells in a different way.

Animals↗