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Biomedical subjects

A Achour

Publications and source records attributed to A Achour.

At least 91 records · Page 5Linked to original sources

Critical sites: a semantic approach to protein sequences. Application to the HIV-1 envelope molecule.

We have designed two software systems allowing the study of proteins through a comparison to those stored in data banks. The first one, "Automat", locates in a systematic manner all identities shared by a given protein and the proteins in a data bank. The second, "Critic" enables the selection of specific segments in a given molecule by comparing them with those gathered in a data bank. These sites were termed "critical" since they mostly correspond to functional sites (active sites) of the well-known proteins which were studied with the aid of this program (somatostatin, insulin, IL2, etc). Automat allowed us to reveal homologies between HIV-1 and the CD4, which have remained unsolved until now. These similitudes proved to be critical sites (according to Critic). The putative involvement of these sites in the physiopathological processes as induced by HIV-1 are worth considering since the results of our experiments are consistent with this assumption.

Amino Acid Sequence↗

Removal of gp160 induced bio-hazards for a safe AIDS vaccine candidate.

In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system--anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1--particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp160 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs.

AIDS Vaccines↗

Cell-mediated immunity against HGP-30, a group-specific peptide of HIV p17 in individuals infected with the AIDS virus.

HGP-30, the synthetic peptide analogue and active component in an HIV-1 (human immunodeficiency virus, type 1) p 17 core-based experimental vaccine, has previously been shown to induce cytotoxic and helper T-lymphocyte responses. In order to further define the T-helper cell responses which are known to play a role in enhancing the immunological response to foreign antigens, we studied the response of individuals infected with HIV to HGP-30 at various stages of disease progression. We have investigated the proliferative cellular response of peripheral blood mononuclear cells (PBMCs) derived from individuals infected with HIV-1 to HGP-30. We have found a PBMC proliferative response to HGP-30 in 40% of the healthy seroconverted patients, in 35% of the CDC stage III patients and in 18% of the CDC stage IV patients. There was no correlation between the proliferative response to HGP-30 and other antigens such as HIV-like proteins or tetanus toxoid not to CD4 cell count. HLA-DR typing revealed the possible presentation of HGP-30 by several different class II molecules. Since these class II molecules occur frequently in the general population, HGP-30 appears to contain broadly reactive epitopes and thus is not restricted as are many peptide vaccines. Due to its broad reactivity and extreme conservation in many HIV-1 strains. HGP-30 is one of the promising candidates for inclusion as a subunit vaccine against HIV-1.

Acquired Immunodeficiency Syndrome↗

[Pregnancy with delivery at term in hemodialyzed women].

Genital disturbances are frequent in chronic renal failure with amenorrhea anovulatory cycles, elsewhere a good hemodialysis improve these disturbances pathogenesis of there; derived from central gonado stimuline dysfunction. We stated 13 pregnancies in our hemodialysed population. Only one successful delivery of a (baby alive and in due time) is registered. Residual diuresis and blood pressure are the most important predictor pregnancy factors in spite of a good dialysance the fetal prognosis in still unclear. Complications were observed in the mother as well as new babies.

Adult↗

A 2-year follow-up of an anti-HIV immune reaction in HIV-1 gp160-immunized healthy seronegative humans: evidence for persistent cell-mediated immunity.

The first trial of an anti-HIV immunization, using a recombinant vaccinia virus expressing gp160 (rV) for priming and paraformaldehyde-fixed rV-infected PBLs and soluble gp 160 for boosting, clearly showed an in vitro HIV-protective immune reaction. This result led us to carry out an additional 2 year Phase I clinical trial in 25 HIV-seronegative volunteers, using HIV gp 160 antigens for immunization in four different protocols. The 2 year trial showed (a) the safety of the preparations, (b) a transient humoral immunity following each boost, and (c) a long-lasting memory T-cell response. Memory cytotoxic T-lymphocytes (CTLs) induced by gp 160 antigen with or without vaccinia vector lysed HLA class I restricted target cells expressing HIV-1 env antigens. These results are consistent with CTLs being an effective component of an AIDS vaccine to control cell-to-cell viral replication, dissemination in the organism, and subsequent evolution toward AIDS.

AIDS Vaccines↗

One-year follow-up of vaccine therapy in HIV-infected immune-deficient individuals: a new strategy.

Immunization of AIDS/ARC patients with autologous cells expressing HIV antigens, although providing clinical and biological benefits, fails to restore cellular immunity. The latter result is due partly to the antiproliferative effect of HIV-1 on activated T-cells (immune suppression), which leads to blockade of specific immune reactions. To overcome immune suppression, a new vaccine strategy was designed consisting of an immunization against HIV-1 combined with components of the T-cell-suppressive (antiproliferative) network. This new vaccine treatment proved to be innocuous in mice, monkeys, and two non-HIV-infected humans. A Phase I clinical trial was performed in six patients previously under cellular immunotherapy and still presenting a cellular immune defect. Preliminary results confirmed, after a 1-year follow-up of the patients, the safety of the new vaccine, which also partially restored the cellular immune response, including anti-HIV HLA-restricted cell-mediated cytotoxicity, delayed hypersensitivity to recall antigens, and proliferation of T-cells specifically activated by recall antigens.

AIDS Vaccines↗

[The effects of high-dose ascorbic acid administration on the factors of lithogenesis in the rat].

Administration of ascorbic acid, at 150 mg/100 ml of water intake, for one month, induced hyperoxaluria in the rats (P less than 0.001) and decreased citraturia (P less than 0.001) magnesuria (P less than 0.001) and pyrophosphaturia (P less than 0.01). The same disorders were observed when the dose administered was 300 mg/100 ml, excepted that oxaluria was considerably enhanced in this group. Despite these variations, renal deposits were not observed, even in the animals receiving 300 mg of ascorbate/100 ml of water intake. This protection was due to decreased calcium excretion (P less than 0.01 in two groups) and probably to acidification of the urine.

Animals↗

[Is sucrose a risk factor in calculus formation?].

The addition of sucrose to drinking water of rats at the rate of 2.5 or 5 grams per 100 ml, for one month, induced hypercalciuria which appeared to be dependent on the degree of supplementation. In spite of these disorders, calcium deposits were not observed in treated animals. This protection against renal calculi was probably due to high urinary excretions of magnesium, phosphorus, zinc and copper. These lithogenesis inhibitors varied, like oxaluria and calciuria, in parallel with dietary sucrose intake.

Animals↗

[Dietetic approach to renal lithiasis].

Because of the diversity and importance of dietary factors in the pathogenesis of renal stones, a nutritional survey must be carried out in order to determine the quantity of protein, calcium, oxalate, sodium, sugar, vitamin D, vitamin C, ingested and the fluid intake and the quality of the drinking water. Although defects are observed in all parameters, it is essential to reduce the intake of protein, calcium, oxalate, sodium, vitamin D, vitamin C as well as increase the sucrose intake and recommend dietary therapy based on mineral water rich in bicarbonate.

Humans↗

[Study of anti-lithogenic action of zinc sulfate in experimental lithiasis in the rat].

Sodium oxalate injected into young rats, via the intraperitoneal route, at a dose of 8 mg per 100 g of body weight, induced death in 50 p. cent of animals, and induced calcium oxalate crystals in renal tissue. When a zinc solution was administered prior to sodium oxalate, at the dose of 12 micrograms/100 g of body weight, the mortality rate decreased, and at the same time oxalate and calcium deposits were significant reduced (respectively P less than 0.01; P less than 0.01). The same results were found when zinc was administered at 24 micrograms/100 g of body weight, however, oxalic accumulation was found to be significantly lower in this group than in the group treated at 12 micrograms. This protection against calcium oxalate deposits was complete in the animals treated with various doses of zinc, because compared to reference animals, which received distilled water, calcium accumulation in these groups was not different and oxalate accumulation was also found to be lower (respectively P less than 0.05; P less than 0.001). Microscopic examination showed calcium crystals only in the group treated with sodium oxalate, localized preferentially in the renal papilla. All these experiments conclude on the total inhibitory effect of zinc on experimental lithiasis induced by oxalic acid, even though it was administered at a dose of only 12 micrograms/100 g of body weight.

Animals↗

[Comparative study between the anti-lithogenic action of zinc and copper against oxalic lithiasis in the rat].

Intraperitoneal injection of sodium oxalate, at the dose of 8 mg/100 g of body weight, induced into rats oxalate and calcium deposits in renal tissue, compared to animals which received distilled water (respectively P less than 0.05; P less than 0.05). However, when a zinc solution was administered previously, at the dose of 24 micrograms/100 g of body weight, oxalate and calcium accumulation was found to be significantly lower than in the group treated exclusively with sodium oxalate. Similar results were found when the metal used was copper, but oxalate accumulation was found to be significantly higher in this group than in the group treated with zinc (P less than 0.01). Compared to reference animals, which received distilled water, oxalate accumulation was found to be significantly decreased in the groups treated with both zinc (P less than 0.001) and copper (P less than 0.01), whereas calcium accumulation was found to be similar. Microscopic examination showed calcium crystals only in the group treated with sodium oxalate, preferentially localized in the renal papilla. These results suggest that zinc and copper, when administered at the dose of 24 mu/100 g of body weight, completely protect against experimental lithiasis induced by oxalic acid. However, the inhibitory effect of zinc was more pronounced than that of copper, especially against oxalate accumulation.

Animals↗

[Primary hypothyroidism and glomerular involvement].

Association between auto-immune dysthyroidism and glomerulonephritis is quite rare. The authors report 3 cases with proteinuria varying from 2.72 to 6.06 g/day and hypothyroidism. Nephrotic syndrome was found in 2 cases and thyroid auto-antibodies (microsomal and thyroglobulin) and circulating immun complexes (C.I.C.) in 1 case, complement fractions C3 and C4 were normal in all cases. Renal biopsy showed membranous glomerulonephritis in 2 cases and minimal lesions in the third case. Proteinuria disappeared with glucocorticoids and thyroxine in 1 case, with thyroxine alone in an other case and persisted in the third case with normal thyroid function.

Adult↗

HGP-30, a synthetic analogue of human immunodeficiency virus (HIV) p17, is a target for cytotoxic lymphocytes in HIV-infected individuals.

Evaluation of the immune response of individuals exposed to human immunodeficiency virus (HIV) is an important component of any plan designed to lead toward the development of an AIDS vaccine. Since the levels of antibodies to HIV p17 and the synthetic p17 peptide HGP-30 correlate with stages of progression to AIDS, studies were initiated to determine whether cytotoxic lymphocytes directed toward target cells pulsed with HGP-30 and radioactive chromium were present in seropositive individuals. The significance of such cells in controlling HIV viral infection has recently been enhanced by reports that HIV p17 is on the surface of infected cells and that an inactivated virus vaccine depleted of viral envelope appears to be effective in controlling expression. The selection of HGP-30 as the p17 peptide to be evaluated in early studies is based on the presence of both T-cell and B-cell epitopes as predicted by computer modeling and mouse studies and the demonstration of in vitro neutralization activity by antibodies to the epitope. By using B-lymphoblastoid cells pulsed with HGP-30 and radioactive chromium as autologous targets and mixed leukocyte culture-expanded peripheral blood lymphocytes as effectors, CD8+ cytotoxic T lymphocytes against HGP-30-coated targets were identified in seropositive individuals. In this report we demonstrate that a synthetic p17 epitope can be a target for major histocompatibility complex-restricted cytotoxic T lymphocytes in HIV-infected individuals.

Cells, Cultured↗