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Biomedical subjects

P Lambert

Publications and source records attributed to P Lambert.

At least 91 records · Page 5Linked to original sources
PubMed1991

The cystine-stabilized alpha-helix: a common structural motif of ion-channel blocking neurotoxic peptides.

Neurotoxic peptides from venoms of scorpions and honey bees exhibit a consensus pattern in the two disulfide bridgings related to the sequence portions Cys-X-Cys and Cys-X-X-X-Cys. A revised three-dimensional structure of charybdotoxin, as determined by two-dimensional nmr spectroscopy, confirms that the consensus cystine dislocation generates in all these toxins a common structural element, i.e., the cystine-stabilized alpha-helical (CSH) motif, which may be correlated with their common ion channel blocking activity.

Amino Acid Sequence↗
PubMed1991

Effect of short- and long-term administration of lithium on the release of endogenous 5-HT in the hippocampus of the rat in vivo and in vitro.

The present study determined the effect of short- (3 days) and long- (21 days) term treatment with lithium on the release of 5-hydroxytryptamine (5-HT) form the hippocampus of the rat, measured both in vivo using microdialysis and in vitro using incubated slices. In the in vivo experiments (on the chloral hydrate-anaesthetized rat) electrical stimulation of the dorsal raphe nucleus for 20 min evoked an increase of 5-HT in dialysates of hippocampus, which both lasted for the duration of the stimulus and was frequency-dependent (2-10 Hz). Electrical stimulation of the dorsal raphe nucleus, at low stimulation pulse frequencies (2 and 3 Hz), released 3-4 fold more 5-HT in rats treated for 3 days with lithium chloride (3 mmol/kg s.c. twice daily), compared to controls. However, the effect of stimulation of the dorsal raphe nucleus was not altered in rats receiving lithium in the diet for 21 days. Basal levels of 5-HT in hippocampal dialysates for rats receiving long- but not short-term treatment with lithium, were significantly lower than controls. In agreement with the in vivo experiments, the in vitro experiments showed that depolarization (high potassium)-evoked release of endogenous 5-HT from slices of hippocampus of rats treated with short- but not long-term administration of lithium was enhanced compared to controls. These experiments provide direct biochemical evidence that short-term treatment with lithium increases depolarization-evoked release of endogenous 5-HT in the hippocampus, an effect which may be related to the rapid antidepressant actions of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Solution synthesis of charybdotoxin (ChTX), a K+ channel blocker.

Charybdotoxin, a 37 amino acid peptide which is a minor component of Leiurus quinquestriatus venom, was synthesized by the solution procedure applying our maximum protection strategy. After formation of the three disulfide bonds, for which a redox buffer was necessary, the final product was purified to homogeneity and found to have similar biological potency to that reported by others for the natural product. The disulfide bond configuration was found to be: Cys7-Cys28; Cys13-Cys33; Cys17-Cys35. Conformational analysis by 1H-NMR showed that the molecule exists as a very tightly folded structure, in which residues 1-7 and 24-37 form a triple-stranded beta-sheet, with a turn at positions 30-31. The region from 11-20 appears to adopt an alpha-helical conformation.

Amino Acid Sequence↗
PubMed1990

Increased expression of Ia antigens on B cells after neonatal induction of lymphoid chimerism in mice: role of interleukin 4.

BALB/c mice rendered chimeric at birth by injection of 10(8) (A/J X BALB/c)F1 spleen cells develop a lupus-like autoimmune disease linked to the activation of donor B cells by host T cells. As in vitro studies previously indicated that interleukin 4 (IL4) was a mediator of the interactions between T and B cells, we analyzed the intensity of Ia antigen expression on B cells of chimeric mice. Flow cytometric analysis with anti-Ia monoclonal antibodies (mAb) revealed that B cells from spleens and lymph nodes of 2-week-old chimeric BALB/c mice displayed a two- to threefold increase in membrane Ia antigen expression, this increase still being present in spleens of 30-week-old animals. An increase in Ia antigen expression was also found in the small number of donor B cells detected in spleens and lymph nodes of chimeric mice. IL4 was the major stimulus leading to increased B cell Ia antigen expression, as this phenomenon was substantially prevented by in vivo treatment of chimeric mice with the anti-IL4 11B11 mAb. In vitro experiments revealed that host splenic T cells of chimeric mice, while unable to generate anti-donor cytotoxic T lymphocytes, secreted significant amounts of IL 4 when stimulated in mixed lymphocyte cultures (MLC) with donor alloantigens. This IL4 secretion led to an increased expression of Ia antigens on donor-type F1 B cells present in MLC. No significant increase in Ia antigen expression was found on syngeneic BALB/c B cells co-cultured with T cells from chimeric mice unless A/J B cells were added to the cultures. Taken together, these findings indicate that increased Ia antigen expression on donor B cells is induced by IL4 secreted by anti-donor T cells. IL4 released in this setting also leads to increased Ia antigen expression on host B cells through a bystander effect.

Animals↗
PubMed1990

[Trimetazidine versus betahistine in vestibular vertigo. A double blind study].

The efficacy of trimetazidine (60 mg/day) in vertigo was compared with that of betahistine (24 mg/day) in a three-month double-blind study. Included in the study were only patients with peripheral vertigo associated or not with tinnitus or hearing loss, and excluded were those presenting with symptoms related to retrocochlear or central disease. Out of the 40 patients enrolled, 20 suffered from Meniere's disease; 4 patients either dropped out of the study or were non-compliant to therapy and could not be taken into account in the final analysis, which bore on 36 patients (18 treated by trimetazidine and 18 with betahistine). There were no dropouts in the Meniere's disease subgroup (10 receiving trimetazidine and 10 receiving betahistine). Results revealed a better response to therapy with trimetazidine in patients suffering from vertigo, and this was particularly true of the Meniere's disease subgroup (p less than 0.025). Moreover, in the latter subgroup, all patients treated with trimetazidine fully recovered from vertigo spells, while these disappeared completely only in 4 of the patients administered betahistine (p less than 0.005). There was no noticeable difference between the two treatment groups as regards the evolution of the accompanying symptoms and the audiometric or vestibular test results. Clinical acceptability was equally excellent in both treatment groups. Overall, this study allowed to confirm the therapeutical efficacy of trimetazidine in the management of vertigo, as well as establishing the clinical advantage of trimetazidine over betahistine in patients suffering from Meniere's disease.

Adult↗
PubMed1988

Autoimmunity and glomerulonephritis after neonatal induction of lymphoid chimerism in mice: role of donor B cells and host T cells.

Balb/c mice neonatally injected with semiallogeneic (A/J x Balb/c) F1 or (C57 BL/6 x Balb/c) F1 hybrid spleen cells develop autoantibodies, marked increase in serum levels of IgG1 and IgE, lymphoid hyperplasia, and immune-complex glomerulonephritis. F1 donor B cells play a dominant role in the pathogenesis of this autoimmune disease since B-cell chimerism is required for the occurrence of immunopathology, donor-specific allotype is expressed on serum anti-DNA antibodies, and substantial amounts of donor-derived immunoglobulins are present in the kidney eluate of chimeric mice. In vitro experiments indicate that T cells from diseased Balb/c mice induce activation of F1 donor B cells with secretion of anti-DNA antibodies. These findings suggest that a host-versus-graft reaction between recipient T cells and donor F1 B cells is responsible for the secretion of pathogenic antibodies in this model.

Animals↗
PubMed1988

Cellular and molecular mechanisms of antiretroviral effects of HPA23.

HPA23 is an antimonio-tungstate that exhibits numerous antiviral activities both in vivo and in vitro. It has been described as a competitive inhibitor of human immunodeficiency virus (HIV) reverse transcriptase (RT). Patients treated with daily injections of HPA23 show an inhibition of HIV RT activity in cell culture in 60% of the cases. Using biophysical (electronic spin resonance [ESR]), ultrastructural (microspectroscopic analysis), chemical (spectroscopy), and biological (cell culture) assays, HPA23 cellular and molecular mechanisms may be summarized as follows: 1) competitive inhibition of HIV-RT, 2) no or slight effect on cells infected with HIV in culture, 3) interactions with the cell membranes when long incubations are performed, and 4) antiviral activity possibly mediated by immune modulator effect of the drug.

Antimony↗
PubMed1988

Hyperactivity of donor B cells after neonatal induction of lymphoid chimerism in mice.

Balb/c mice made chimaeric by neonatal injection of semi-allogeneic (A/J x Balb/c)F1 hybrid spleen cells develop anti-DNA and rheumatoid factor-like antibodies in the context of hypergammaglobulinaemia with marked elevation of IgG1 and IgE serum levels. Chimaeric mice also display increased levels of antibodies to different haptens and to tobacco mosaic virus (TMV). The allotypic marker of the A/J strain is present on anti-DNA and anti-hapten antibodies. In addition, spleen cells of chimaeric mice spontaneously produce high levels of IgG1 and anti-DNA antibodies in vitro and this hyperactivity is abolished after lysis of donor lymphocytes. These findings indicate that polyclonal activation of donor B cells plays an important role in this model of autoimmunity.

Animals↗
PubMed1987

The nursing process: the effect on patients' satisfaction with nursing care.

This study compares the effects of the nursing process and traditional care in a patient population where the environment, nurses, other multidisciplinary team members and the nursing model were the same for two patient groups. Both groups were nursed using traditional therapeutic community techniques. One group also received care using a nursing process approach. Patients in the nursing process group did not feel nurses were significantly more therapeutic nor were they more satisfied with their care.

Consumer Behavior↗
PubMed1987

Pregnancy and humoral immune response in mice chronically infected by Trypanosoma cruzi.

The effect of pregnancy on the humoral immune response induced by Trypanosoma cruzi was studied in groups of chronically infected and pregnant mice (IP) or chronically infected and nonpregnant mice (INP) of strain BALB/c. Groups of noninfected and nonpregnant mice (NINP) or noninfected and pregnant mice (NIP) served as controls. The pregnant mice were killed on day 17 of pregnancy. Anti-T. cruzi immunoglobulin G (IgG) and IgM antibodies, detected by immunofluorescence or enzyme-linked immunosorbent assay or both, underwent a pregnancy-associated decrease of 20 to 40%, whereas complement-mediated lytic antibodies were unaffected by pregnancy. Immunoblotting analysis indicated identical specificities of the anti-T. cruzi antibodies in IP and INP groups. The levels of all the immunoglobulin isotypes (particularly IgG2a and IgG3), circulating immune complexes, rheumatoid-like factor, and anti-DNA antibodies were considerably increased during chronic infection (NINP versus INP), which could be related to the high degree of polyclonal B-cell activation occurring in T. cruzi infection. However, pregnancy significantly decreased (by 20 to 60%) such parameters. IgG levels were particularly affected (by 40 to 60%), and the decreases could be ordered as follows: IgG3 greater than IgG2a greater than IgG1 greater than IgG2b for IP versus INP. Comparisons between the noninfected groups indicated differences only in IgG levels. These results indicate the following. (i) The specific humoral anti-T. cruzi immune response is weakly affected by pregnancy, which is not sufficient to modify the course of the mother's infection. (ii) Pregnancy does not modify the expression of the anti-T. cruzi antibody repertory. (iii) Pregnancy reduces the polyclonal B-cell activation, particularly the levels of the IgG isotypes undergoing the greatest activation.

Animals↗
PubMed1987

Autoimmune disease after neonatal injection of semi-allogeneic spleen cells in mice: involvement of donor B and T cells and characterization of glomerular deposits.

Balb/c neonates injected with semi-allogeneic (A/J x Balb/c) F1 hybrid spleen cells develop an autoimmune disease associated with an immune-complex glomerulonephritis. The successful induction and maintenance of B cell chimerism is required for the occurrence of autoimmunity. The percentage of chimeric mice displaying autoimmune features increases in parallel with the number of cells injected at birth. T cell depleted inocula although readily inducing B cell chimerism were found unable to induce hypergammaglobulinaemia, circulating immune complexes and glomerulonephritis. IgG1 is the most and IgG3 the least represented IgG isotype among the immunoglobulins deposited in the glomeruli. Immunoglobulins bearing donor (A/J) allotype are detected in the glomeruli of six out of 11 chimeric mice. Rheumatoid factor activity is significantly concentrated within the immunoglobulins eluted from the kidneys, whereas anti-DNA activity is not.

Animals↗