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J Ang

Publications and source records attributed to J Ang.

11 recordsLinked to original sources
PubMed2001

Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability.

Nitric oxide (NO) plays a critical role in vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular hyperpermeability. However, the relative contribution of different NO synthase (NOS) isoforms to these processes is not known. Here, we evaluated the relative contributions of endothelial and inducible NOS (eNOS and iNOS, respectively) to angiogenesis and permeability of VEGF-induced angiogenic vessels. The contribution of eNOS was assessed by using an eNOS-deficient mouse, and iNOS contribution was assessed by using a selective inhibitor [l-N(6)-(1-iminoethyl) lysine, l-NIL] and an iNOS-deficient mouse. Angiogenesis was induced by VEGF in type I collagen gels placed in the mouse cranial window. Angiogenesis, vessel diameter, blood flow rate, and vascular permeability were proportional to NO levels measured with microelectrodes: Wild-type (WT) > or = WT with l-NIL or iNOS(-/-) > eNOS(-/-) > or = eNOS(-/-) with l-NIL. The role of NOS in VEGF-induced acute vascular permeability increase in quiescent vessels also was determined by using eNOS- and iNOS-deficient mice. VEGF superfusion significantly increased permeability in both WT and iNOS(-/-) mice but not in eNOS(-/-) mice. These findings suggest that eNOS plays a predominant role in VEGF-induced angiogenesis and vascular permeability. Thus, selective modulation of eNOS activity is a promising strategy for altering angiogenesis and vascular permeability in vivo.

Animals↗
PubMed1998

Size and number of epithelial cells washed from the cornea after contact lens wear.

Using the technique of Fullard and Wilson, tear samples were collected atraumatically from the corneas of 14 rigid gas permeable (RGP) contact lens wearers, 14 soft contact lens (SCL) wearers, and 22 controls who did not wear contact lenses. Samples were analyzed for the number, size, and contiguity of the cellular contents. Both RGP and SCL groups had, on average, significantly fewer cells per sample than controls (median values were 11 and 12 cells vs. 44). The difference remained significant even after a correction of three cells was applied to account for cells adherent to the lenses. Approximately 80% of epithelial cells from both lens wear and control eyes were found in isolation, whereas 20% were contiguous with 1 or 2 other cells. This result is compatible with the majority of epithelial cells having exfoliated from the surface of the cornea after detaching from their neighbors, rather than detaching in sheets of cells. The cell length and cell area were analyzed. RGP wearers had significantly smaller cells than controls, whereas SCL wearers had slightly (but significantly) larger cells. These results may reflect changes in the exfoliation mechanism of the corneal epithelium in contact lens wear.

Cell Count↗
PubMed1996

ZP3 peptide vaccine that induces antibody and reversible infertility without autoimmune oophoritis.

Autoantibodies to ZP3, a major glycoprotein of the zona pellucida (ZP) with sperm receptor function, can block sperm/oocyte interaction. However, only mice of certain major histocompatibility complex (MHC) haplotype respond to the ZP3 peptide. Moreover, ZP3-specific T cells can mediate ovarian autoimmune disease. A chimeric peptide has been designed that induces antibody to native ZP3 regardless of the MHC haplotype of the inbred mice tested. This results in reduction in fertility that is reversible. Infertility correlates well with ZP antibody titer, and the mice do not develop concomitant autoimmune oophoritis. The vaccine contains (1) a promiscuous foreign T-cell peptide capable of eliciting a T-cell response regardless of the animals' MHC haplotype, and (2) a modified native B-cell peptide of ZP3.

Animals↗
PubMed1996

Influence of autoimmune ovarian disease pathogenesis on ZP3 contraceptive vaccine design.

Zona pellucida (ZP) glycoproteins possess sperm receptor-binding activities. Antibodies against ZP can block sperm-egg interaction and thereby prevent fertilization. The feasibility of developing a safe contraceptive vaccine based on the ZP has been hampered by the finding that active immunization with autologous or heterologous ZP proteins results in infertility that is associated with ovarian dysfunction. A mouse model was used to investigate mechanisms of the ovarian pathology that is induced by active immunization with a 13mer peptide derived from mouse ZP3 (mZP3(330-342)). This peptide includes one native B-cell epitope and two nested T-cell epitopes. Ovarian pathology could be transferred into naive recipients by CD4+ T cells, but not by antibodies, from immunized mice, suggesting the importance of T cells in the mechanism of ovarian pathogenesis. Moreover, immune responses, as well as disease induction, were restricted to H-2a,k,u,s,axb haplotypes. On the basis of this mouse model, a strategy to generate a contraceptive anti-ZP antibody response without a pathogenic T-cell response, irrespective of H-2 haplotype, is described. The B-cell epitope was modified by amino acid substitution to eliminate the overlapping oophoritogenic T-cell epitope, and was linked to a promiscuous foreign T-cell epitope, bovine RNase94-104. The resultant chimaeric peptide (CP2) induced anti-ZP antibodies in 100% of the eight strains of inbred mice with different H-2 haplotypes without significant disease induction. An antifertility trial in B6AF1 female mice immunized with CP2 showed that the anti-ZP antibody was associated with a reduction in fertility. This infertility was reversed with a decline in anti-ZP antibody titre. Preliminary data show that this strategy of vaccine design may also be applied to primates.

Amino Acid Sequence↗
PubMed1995

A zona pellucida 3 peptide vaccine induces antibodies and reversible infertility without ovarian pathology.

Zona pellucida 3 (ZP3) is a major glycoprotein of the zona pellucida that possesses the sperm receptor function. ZP3 induces autoantibody that can block sperm/oocyte interaction. However, the feasibility of a ZP3 contraceptive vaccine has been marred by the finding that ZP3-specific T cells mediate ovarian autoimmune disease. Moreover, as reported in this work, only some inbred mouse strains respond to the ZP3 peptide. We now describe a chimeric peptide that induces Abs to native ZP3 regardless of the MHC haplotype of the inbred mice tested. Study in one mouse strain resulted in reduction in fertility that correlates well with zona pellucida Ab titer, and most importantly, the mice do not develop concomitant autoimmune oophoritis. Moreover, the infertility was completely reversible. The design of the vaccine chimeric peptide is governed by the inclusion of two essential components: 1) a promiscuous foreign T cell peptide capable of eliciting a Th cell response regardless of the MHC haplotype of the animals, and 2) the native B cell peptide of ZP3 that has been modified by substitution of residue(s) critical for T cell but not B cell response to ZP3.

Amino Acid Sequence↗
PubMed1994

Contraceptive vaccine assessment based on a murine ZP3 mini-autoantigen.

A summary is presented of published and some unpublished observations from studies on the immunological response of mice to a 13-mer peptide of the murine ovarian zona pellucida glycoprotein ZP3. The findings have the following implications for the design of immunocontraceptive vaccines. To be reversible, a ZP3 vaccine must not contain pathogenic T cell epitopes of ZP3, but contraception without autoimmune oophoritis may be feasible. The immune response to the ZP3 mini-autoantigen is highly variable among inbred mouse strains, suggesting that a single oophoritogenic peptide would not achieve irreversible contraception in an outbred population. The discovery of antigen mimicry at the level of T cell peptide has thrown doubt on the validity of current strategy in detecting relevant self-antigens that might cross react with vaccine immunogens and on the feasibility of fully predicting the cross-reactive autoimmunogenic potential of a peptide or polypeptide vaccine antigen. Autoantibodies directed against epitopes outside the ZP3 mini-autoantigen, produced by immunization with the pure T cell epitope, react with high affinity, with native zona pellucida, and may be useful in identifying B cell epitopes in ZP3.

Amino Acid Sequence↗
PubMed1985

A comparison of the acute effects of dextroamphetamine and fenfluramine in depression.

Fenfluramine (Fen) 40 mg, a selective releaser of serotonin, and dextroamphetamine (Dex) 15 mg were administered in a double-blind crossover design to 16 subjects with major affective disorder, depression. Three hours after administration both drugs significantly improved depression and improved vigor, fatigue, and confusion-bewilderment on the subscales of the Profile of Mood States. Dex was significantly better than Fen only on the vigor and fatigue subscales. Other data from this study suggest that when used acutely Fen can mimic long-term antidepressant effects, whereas the acute effects of Dex are similar to its stimulating effects in normals.

Adult↗
PubMed1982

The role of attitudes and social norms in adolescent cigarette smoking.

Measures of attitude and social norm (pressure) were gathered from 279 young people aged 14-16 attending one North Island high school. These data were analysed according to Fishbein's model of behavioural intention to determine the relative importance of attitudes and social pressures in young people's intentions to smoke cigarettes. New Zealand data are compared from a comparable group of US adolescents. Results clearly indicate that social pressures were much more important in determining intention to smoke cigarettes among the New Zealand sample than among the US sample. Among the New Zealand sample, there was less difference between the attitudes towards cigarette smoking of those who intend to smoke and those who do not than there was among the US sample. These New Zealand data are interpreted in terms of developing educational programmes to reduce adolescent cigarette smoking.

Adolescent↗
PubMed1977

Chemotherapy studies in autochthonous rat tumors. Forestomach and bladder cancer.

Acetoxymethyl-methyl-nitrosamine (AMMN) induced only carcinomas of the forestomach in female Sprague-Dawley rats after an induction time of about 100 days when applied orally twice weekly in single doses (d) of 3.5 mg/kg body weight, Butyl-butanol-nitrosamine (BBN) selectively produced bladder tumors in female Sprague-Dawley rats after about 280 days when given in daily oral single doses (d) of 10 mg/kg body weight. The reactions of a total of 520 rats with chemically induced tumors were tested using 4-drug combination chemotherapy with different equitoxic doses of Adriamycin (Adm), Methotrexate (Mtx), 5-Fluorouracil (5-FU) and Bleomycin (Blm). The influences of combined therapy on mean sruvival time, tumor weight, histology of tumors, and adverse side effects of therapy are herein described. The results showed to be tumorspecific. In addition, the comparability of experimental chemotherapy in autochthonous rat tumors to clinical experience is discussed.

Animals↗