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Biomedical subjects

D Quintana

Publications and source records attributed to D Quintana.

9 recordsLinked to original sources
PubMed2001

Plasmid DNA-recombinant Opc protein complexes for nasal DNA immunization.

The nasal mucosa may provide a simple, non-invasive route to deliver DNA encoding genes that stimulate a specific immune response. Based on this, a new approach using pCMVbeta-gal plasmid DNA complexed to the Opc meningococcal outer membrane protein was assayed for. Optimal conditions of interaction were established between recombinant Opc protein and pCMVbeta-gal plasmid DNA. Complexes were fully characterized by electrophoresis analysis, DNAse resistance assay and transmission electron microscopy. DNA-protein complexes were also evaluated in in vitro transfection experiments. After the characterisation of complexes, Balb/c mice were intranasal (i.n.) and intramuscularly (i.m.) immunized. The humoral immune response against beta-galactosidase was measured by ELISA. The proliferative response in the spleen lymph nodes was also measured. Complexes administered by i.n. route induced both systemic and mucosal antibody responses. This behavior was not observed with the naked DNA. Finally, a lymphoproliferative response specific to beta-galactosidase induced by DNA-protein complexes was also detected.

Administration, Intranasal↗
PubMed2001

Multivalent DNA-based immunization against hepatitis B virus with plasmids encoding surface and core antigens.

The immune response against hepatitis B surface and core antigens was evaluated by either coinoculation or independent intramuscular administration of pAEC compact DNA immunization vectors carrying their genes. The pAEC vectors bear just the essential elements for mammalian expression and bacterial amplification. Balb/c mice were immunized with 100 microg of each construct, either alone or in combination. In spite of lacking known immunostimulatory sequences (e.g., AACGTT), significant cellular (proliferative) and humoral immune responses were raised against both antigens. Coadministration of both plasmids maintained the immune response against the two antigens, without interference between them. Modulation of the antigen expression and further immune response, by using the Kozak's translation initiation sequence, was also analyzed. No differences due to its presence or absence were observed.

Animals↗
PubMed2001

Improved prognostication of renal cell carcinoma using an integrated staging system.

PURPOSE: To integrate stage, grade, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) into a clinically useful tool capable of stratifying the survival of renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: The medical records of 661 patients undergoing nephrectomy at University of California Los Angeles between 1989 and 1999 were evaluated. Median age was 61 years, male-to-female ratio was 2.2:1, and median follow-up was 37 months. Survival time was the primary end point assessed. Sixty-four possible combinations of stage, grade, and ECOG PS were analyzed and collapsed into distinct groups. The internal validity of the categorized was challenged by a univariate analysis and a multivariate analysis testing for the accountability of each UCLA Integrated Staging System (UISS) category against independent variables shown to have impact on survival. RESULTS: Combining and stratifying 1997 tumor-node-metastasis stage, Fuhrman's grade and ECOG PS resulted in five survival stratification groups designated UISS, and numbered I to V. The projected 2- and 5-year survival for the UISS groups are as follows for the groups: I, 96% and 94%; II, 89% and 67%; III, 66% and 39%; IV, 42% and 23%; and V, 9% and 0%, respectively. UISS accounted for the significant variables in the variate analysis. CONCLUSION: A novel system for staging and predicting survival for RCC integrating clinical variables is offered. UISS is simple to use and is superior to stage alone in differentiating patients' survival. Our data suggests that UISS is an important prognostic tool for counseling patients with various stages of kidney cancer. Further prospective large-scale validation with external data is awaited.

Adult↗
PubMed2001

Study of different coupling agents in the conjugation of a V3-based synthetic MAP to carrier proteins.

The conjugation of synthetic peptides to carrier proteins is a widely used method for immunological studies. Different coupling agents have been described to form the conjugate with carrier proteins. In this paper, we demonstrate that the antibody response toward V3-based synthetic MAPs derived from HIV-1, JY1 isolate, conjugated to two different carrier proteins using either m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) or beta-maleimidopropionic acid N-hydroxysuccinimide ester (MPS), or succinic anhydride (SA) show different behaviors. An excellent anti-JY1 response without a strong response to the coupling agent is observed in the case of succinic anhydride spacer. In contrast, MBS produces total abrogation of the antibody response with a high response toward the coupling agent.

Animals↗
PubMed2000

Immunogenicity comparison of a multi-antigenic peptide bearing V3 sequences of the human immunodeficiency virus type 1 with TAB9 protein in mice.

The multiple antigenic peptide system (MAP) has been proposed as a novel and valuable approach for eliciting antibodies for peptides and developing synthetic vaccines. Multi-epitope polypeptides (MEP) have also been developed as an alternative to the recombinant approach for vaccines. The V3 loop from the HIV type 1 (HIV-1) external glycoprotein (gp120) contains the principal neutralization domain (PND). Antibodies against this region neutralize HIV-1 in vitro and in vivo. In this work, a novel presentation of di-epitope MAP was synthesized. A monomeric MAP carrying two identical JY1 V3 sequences as B-cell epitopes and the 830-843 region of tetanus toxoid as a T-helper cell epitope was synthesized. This basic structure was covalently linked to produce a four-JY1-branched homodimer (JY1-MAP4). Additionally, six different monomeric MAPs, bearing four copies of V3 from isolates LR150, JY1, RF, MN, BRVA and IIIB, were synthesized. These monomers were conveniently linked among themselves to produce homodimeric and heterodimeric MAPs of eight V3 branches (V3-MAP8). JY1-MAP8 elicited higher antibody titers in Balb/c mice than JY1-MAP4. The immunogenicity of two different, hexavalent V3-MAP8 mixtures and the MEP TAB9, which tandems the same six V3 sequences in a single molecule, were compared. The antibody response against the mixtures of the heterodimeric MAP showed a wider recognition pattern of the V3 region, while the homodimeric cocktail showed an intermediate pattern. Antibodies elicited by TAB9 recognized only the JY1, LR150 peptides. These results emphasize the influence of V3 epitope presentation upon the characteristics of the antibody response generated.

Amino Acids↗
PubMed1999

A prime-boost regime that combines Montanide ISA720 and Alhydrogel to induce antibodies against the HIV-1 derived multiepitope polypeptide TAB9.

A phase I clinical trial with the HIV-1-derived multi-epitope polypeptide (MEP) TAB9 in the oil adjuvant Montanide ISA720 (M-ISA720) was recently performed. Although severe local reactions were reported after the second and third injections of this vaccine candidate, the first inoculation was well tolerated. In this article we evaluated a prime-boost regime consisting of one inoculation of TAB9 in M-ISA720 followed by a booster with the same antigen in aluminum hydroxide. This combination of adjuvants elicited similar antibody levels in rabbits than the traditional two-dose schedule with M-ISA720. A control group injected three times with TAB9 in aluminum hydroxide developed markedly lower antibody titers. These results showed that although oil adjuvants are better than alum for priming the immune system for antibody production against TAB9, both kinds of adjuvants can be equally effective in booster immunizations. Therefore, by using the more reactogenic oil adjuvant only for priming, we should be able to eliminate the undesirable reactions characteristic of these compounds while achieving equivalent levels of specific antibodies.

AIDS Vaccines↗
PubMed1997

Urinary calcium excretion in healthy school children.

Two hundred and twenty Argentinian primary school children (122 boys, 98 girls, aged 6-13 years) were studied to establish reference values of 24-h urinary calcium excretion (UCa) and calcium/creatinine ratio (Ca/Cr) in 24-h urine collections and in first-morning urine samples. Mean UCa excretion was 2.05 +/- 1.40 mg/kg per day and the 95th percentile was 4.74 mg/kg per day. UCa excretion was higher in boys than girls (2.33 +/- 1.47 and 1.70 +/- 1.24 mg/kg per day respectively, P < 0.001). Statistically significant differences were found between the 6- to 9-year and the 10- to 13-year age groups (2.37 +/- 1.49 vs. 1.73 +/- 1.25 mg/kg per day, P < 0.001). Mean Ca/Cr ratios in 24-h collections and in first-morning urine samples were 0.129 +/- 0.086 and 0.105 +/- 0.079 for the group overall (P < 0.001). The Ca/Cr ratio in the first-morning urine sample correlated poorly with the 24-h calcium excretion, suggesting that the Ca/Cr ratio in first-morning urine samples cannot replace the 24-h measurement.

Adolescent↗
PubMed1997

Broadly reactive antibodies against a gp120 V3 loop multi-epitope polypeptide neutralize different isolates of human immunodeficiency virus type 1 (HIV-1).

A gene encoding for a novel multi-epitope polypeptide (TAB4) was synthesized and expressed in Escherichia coli. The protein was composed of 15 amino acid fragments derived from the V3 loop of HIV-1 isolates MN, IIIB, RF, JY1, BRVA and LR150, joined by five-amino-acid linkers. Immunogenicity of TAB4 in rabbits was studied, and the antibody response against individual peptides investigated. TAB4 was shown to be immunogenic in Complete Freund's Adjuvant in a dose-dependent manner, and was able to elicit a humoral response against all V3 epitopes included on the protein. Sera from some of the animals were able to neutralize the replication of viral strain MN, and in one case IIIB, with moderate titers. Some sera also neutralized several Cuban clinical strains, isolated in peripheral blood mononuclear cells, after one round of amplification in MT4 cells.

Amino Acid Sequence↗