Search PubMed⌕ Search

Biomedical subjects

C Griscelli

Publications and source records attributed to C Griscelli.

At least 91 records · Page 5Linked to original sources
PubMed1990

Germ-line mosaicism simulates genetic heterogeneity in Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome (IMD2) is an X-linked recessive immunodeficiency. Initial linkage studies mapped the disease locus on the proximal short arm of the X chromosome, a localization which was further refined to the interval framed by DXS7 and DXS14. We have recently shown that a novel hypervariable locus, DXS255, is very closely linked to the disease gene and is likely to be, at present, the marker closest to the disease gene. The analysis of one family, however, displayed conflicting linkage results, as all of the informative markers situated in the Xp11-q22 region appeared to recombine with the disease locus in two "phase-known" meioses. We have shown by X-inactivation studies that the segregation of the disease through three obligate carrier females in this family originates from a grandpaternal mosaicism, which accounts for the apparent recombinations. This shows that germ-line mosaicism can simulate genetic heterogeneity in linkage studies.

Blotting, Southern↗
PubMed1990

[Hypogammaglobulinemia G and A with hypergammaglobulinemia M. Apropos of 12 cases].

Hyper IgM with low IgG and IgA is a rare humoral immunodeficiency. We presently report 12 new observations which have been clinically and immunologically studied. On one occasion the syndrome was found to be associated with congenital rubella. Since 10/12 children were male, X-linked inheritance is suggested which has been confirmed in 2 cases. In most cases (9/12), the first infections occurred within the first year of life. The syndrome is causing upper and lower respiratory tract infections due to bacteria, as well as gut infections. Lymphoid organ hyperplasia has been noted in 11/12 patients. Polyclonal hyper IgM serum contrasts with low or absent IgG, IgA and IgE. In some instances, some IgM antibody response was detected. A dysfunction of cellular immunity was not detected. Autoimmunity was detected in 3 patients. Finally, transient neutropenia occurred in 50% of the patients. Intravenous immunoglobulin G substitution treatment resulted in a significant reduction in the occurrence of infections as well as in normalization of growth rate. Immunoglobulin infusion also frequently induced correction of hyper IgM and neutropenia.

Antibody Formation↗
PubMed1989

Inversion of chromosome 7 in ataxia telangiectasia is generated by a rearrangement between T-cell receptor beta and T-cell receptor gamma genes.

Specific and recurrent chromosomal rearrangements are often observed in the karyotypes of phytohemagglutinin-stimulated lymphocytes. The percentage of cells demonstrating these rearrangements is dramatically increased in the genetic disease ataxia telangiectasia. Inversion of chromosome 7 represents approximately half of the chromosomal rearrangements in this disease. Because the chromosomal locations of the inv(7) breakpoints coincide precisely with those of the T-cell antigen receptor (TCR) beta and gamma genes, it has been hypothesized that this rearrangement may occur by recombination between those two loci. Here, we present direct evidence that inversion of chromosome 7 in ataxia telangiectasia is generated by site-specific recombination between a TCR gamma variable segment and a TCR beta joining segment.

Ataxia Telangiectasia↗
PubMed1989

Development of immunologic functions after bone marrow transplantation in 33 patients with severe combined immunodeficiency.

We retrospectively analyzed the development of lymphocytes and of the main immunological functions in 33 patients with severe combined immunodeficiency who survived at least 6 months after bone marrow transplantation (BMT). Eighteen patients received HLA-identical BM and 15 received HLA-nonidentical BM. Development of immune functions occurred faster after HLA-identical BMT as full T- and B-lymphocyte-mediated responses were present at day 186 versus 505, respectively (P = .05). In addition, antibody responses remain completely or partially absent in 8 of 15 patients of the second group. Detection of antibody response after HLA-incompatible BMT correlated with engraftment of donor B cells in informative cases. In patients who received an HLA-nonidentical BMT after chemotherapy (6 of 15), development of immune functions occurred more rapidly and 6 of 6 had B-cell functions, including normal antibody production. Autoimmunity was not uncommon and was found after HLA-incompatible BMT (4 of 15) or after HLA-partially phenotypically identical BMT (2 of 3). Antibodies were in most cases specific for blood cells. Occurrence of autoimmunity correlates with poor B-cell functions and to a lesser extent with defective T-cell responses. This type of study may lead to definition of a more accurate strategy for performing BMT in patients with severe combined immunodeficiency.

Adolescent↗
PubMed1989

Hypoglycaemia induced by antibodies to insulin receptor following a bone marrow transplantation in an immunodeficient child.

Severe hypoglycaemia developed seven months after a bone marrow transplantation in a child with severe combined immunodeficiency. His serum exerted potent insulin-like activity: (a) it stimulated insulin receptor autophosphorylation and kinase activity in cell-free systems, this effect being additive to insulin; (b) it increased glucose transport in isolated soleus muscle. These insulin-like effects were due to immunoglobulins against the insulin receptor. Indeed, the patient serum immunoprecipitated human or murine insulin receptors from different tissues and inhibited insulin binding to receptor on human IM-9 lymphocytes. After corticoids and immunosuppressive therapy by azathioprine, the patient hypoglycaemic episodes disappeared, and concomitantly, the antibodies to insulin receptor were no longer detected, as judged by both immunoprecipitation of insulin receptor and stimulation of glucose transport.

Animals↗
PubMed1989

Effects of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on the expression of LFA-1 in the moderate phenotype of leukocyte adhesion deficiency (LAD).

Leukocyte adhesion deficiency (LAD) is a recessive autosomal disease characterized by life-threatening recurrent bacterial infections, associated with defective functions of leukocytes due to deficient membrane expression of leukocyte adhesion glycoproteins. These proteins, LFA-1, Mac-1 (CR3), and p150,95 are alpha 1 beta 1 heterodimers composed of different alpha chains noncovalently associated with a common beta chain. Patients with the severe phenotype of the disease completely lack the three glycoproteins on leukocyte surfaces, while patients with the moderate phenotype can express low levels of leukocyte adhesion proteins (1-10%). We have studied a patient with the moderate phenotype of LAD. Polymorphonuclear functions such as chemotaxis and adherence were altered, natural killer activity was low, and cytotoxic T-lymphocyte activity was abolished. Previous biochemical studies showed a conserved synthesis of both the LFA-1 alpha-chain precursor and the beta-chain precursor with, occasionally, some amount of alpha-beta complexes in the cytosol. beta chain-specific mRNA transcripts of normal size were detected at normal levels in patients' cells. Attempts to increase the transcription of the beta gene by in vitro treatment with TNF-alpha or IFN-gamma were successful but did not result in increased membrane expression of the alpha-beta complexes.

Antigens, Differentiation↗
PubMed1989

Activation of genetically major histocompatibility complex (MHC) class II-deficient B lymphocytes.

It has been suggested that MHC class II molecules can transduce signals required for B-cell activation. Enhancement or inhibition of B-cell stimulation by anti-MHC class II molecule antibodies has likewise been reported. The study of B cells from patients with a combined immune deficiency due to a defective expression of MHC class II genes provides a useful tool for approaching the functional role of B-cell HLA class II molecules. We have thus analyzed the specific and nonspecific, cognate and noncognate B-cell activation of genetically HLA class II-deficient lymphocytes. B lymphocytes from 14 tested patients were able to synthesize RNA following stimulation with ionomycin and phorbol myristate acetate or anti-mu antibodies and with mannan, a T cell-independent polysaccharidic antigen. They were also able to synthetize DNA following the addition of ionomycin and PMA or of anti-mu antibodies in the presence of recombinant interleukin 2. Pokeweed mitogen failed to induce B-lymphocyte terminal differentiation into immunoglobulin-producing cells in the presence of normal T lymphocytes, while a combination of anti-CD2 antibodies were capable of triggering IgG synthesis. B-cell activation, whatever the condition used, did not induce HLA class II expression. Mannan-specific T cell-dependent antibody production (IgM) was detected in 6 of 14 patients. Anti-influenza virus antibody production was always found absent. These results are compatible with the hypothesis that B-cell activation events that do not require a cognate interaction with T cells can occur in the absence of HLA class II molecule expression, while the absence of HLA class II molecule expression prevents T-B cognate interaction.

Adolescent↗
PubMed1989

Combined immunodeficiency with abnormal expression of MHC class II genes.

The MHC class II CID represents an example of immunodeficiency in which the defect in expression of membrane glycoproteins leads to abnormal cell to cell interactions and thus to abnormal immune responses. It represents an interesting model which confirms the importance of MHC molecules in all immune responses to foreign antigens. It also underlines the complexity of regulatory mechanism which control the expression of MHC class II genes. To elucidate these mechanisms, it is essential to identify and characterize the genes involved in control of MHC class II expression.

Agammaglobulinemia↗
PubMed1989

Serum IgG subclass levels in patients with primary immunodeficiency syndromes or abnormal susceptibility to infections.

Serum IgG subclass levels were measured using an indirect competitive immunoenzymatic assay with monoclonal antibodies in 221 patients affected with definite immunodeficiency (ID) syndromes and 229 patients presenting with infection patterns suggestive of ID, but with normal immunoglobulin class levels and no clear evidence of ID. In common variable ID and IgG-IgA deficiency with normal or high IgM, subclass imbalance (mostly IgG1-IgG3 or IgG2-IgG4 deficiency) was the rule, with a higher incidence of severe infections in IgG2-IgG4 defects. One-fifth of patients with IgA deficiency, especially those with autoimmune cytopenia, had subclass deficiencies with no significant correlation with the occurrence of infections. Subclass (mostly IgG2-IgG4) deficiencies were also observed in severe combined ID, defective expression of HLA class II antigens, chronic mucocutaneous candidiasis, and IgM deficiency. Subclass levels were normal in all but one (who was IgG3 deficient) patient with the Wiskott-Aldrich syndrome and in the Buckley's syndrome, except for an unusual patient who presented with low IgG and IgA levels. Subclass (mainly IgG2) deficiency occurred in 24% of infected patients without known ID.

Autoimmune Diseases↗
PubMed1989

Cost of allogeneic bone marrow transplantation in four diseases.

The cost of bone-marrow transplantation is compared in 4 diseases: acute myelogenous leukaemia, severe combined immunodeficiency, severe aplastic anaemia and chronic granulocytic leukaemia. Hospital cost components directly related to the clinical protocols applied are valorized. Results confirm the well-known fact that bone-marrow transplantation is a costly technique. The unit cost of a transplantation can vary from 1 to 2 between departments for the sole reason that patients treated are not suffering from the same illness. For one disease, the unit cost may vary from 1 to 2.7 when post-graft complications arise. Furthermore, in the health-care sector, as well as in every other economic sector, costs do not remain stable: they vary in time most especially when treatment protocols evolve. This type of cost information is the basis for management control systems without which physicians, hospital managers and health-care authorities cannot communicate effectively. In countries where health care is largely financed by the community, what is at stake is the future of advanced technologies in medicine.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Incidence, severity, and prevention of infections in chronic granulomatous disease.

We retrospectively analyzed the frequency and nature of infections occurring in 48 patients with chronic granulomatous disease. The long-term use of trimethoprim-sulfamethoxazole and ketoconazole as a preventive therapy for infections has also been evaluated. Lymphadenitis, lung infections, dermatitis, enteral infections, and hepatic abscesses were the most frequent infections. Staphylococcus aureus, Salmonella, and Aspergillus were the main microorganisms encountered. Twelve patients died: five from lung aspergillosis, three from hepatic abscesses, two from pneumonopathy of unknown origin, one from salmonellosis, and one from another probable infection that could not be proved. The actuarial survival rate was 50% at 10 years of age, with a prolonged plateau thereafter. There was no difference in survival rates between patients with X-linked and those with autosomal recessive chronic granulomatous disease. The 8-year actuarial survival rate was significantly higher for patients born in 1978 or afterward than for patients born before 1978 (92.9% vs 70.5%). A retrospective analysis of the occurrence of bacterial and fungal infections in patients who received trimethoprim-sulfamethoxazole and ketoconazole as infection prophylaxis indicated that the former was effective against bacterial infections but that ketoconazole provided no protection against Aspergillus infections.

Adolescent↗
PubMed1989

Mother-child transmission of HIV-1 and infant survival in Brazzaville, Congo.

The aim of this study was to compare the probability of survival of infants born to anti-HIV-1-positive and anti-HIV-1-negative mothers. One thousand, eight hundred and thirty-three pregnant women, recruited sequentially in two mother-child clinics in Brazzaville, were screened for anti-HIV-1 (by enzyme-linked immunosorbent assay with confirmation by Western blot). Each seropositive mother (71 out of 1833, 3.9%) was matched for age, presumed date of delivery and place of residence with two seronegative mothers. Sixty-four babies born to anti-HIV-1-positive mothers and 130 control babies born to anti-HIV-1-negative mothers were followed up for 12-22 months (mean, 18 months). The probabilities of survival were estimated by the Kaplan-Meier method. At birth, the two groups of babies did not differ with regard to rate of stillbirths, gestational age, sex ratio and weight. Among babies born to seropositive mothers, the probability of survival was 0.87 (s.d. 0.04) at 3 months, 0.71 (s.d. 0.06) at 6 months, 0.68 (s.d. 0.06) at 9 months and 0.61 (s.d. 0.06) at 12.5 months. In the controls the probability of survival was 0.98 (s.d. 0.01) at 3 months and 0.97 (s.d. 0.02) at 12 months. The excess of mortality in the babies born to anti-HIV-1-positive mothers is highly significant (P less than 0.001). The deaths occurred more frequently and earlier than in similar cohort studies performed in developed countries.

Age Factors↗
PubMed1989

[Prognostic factors in HIV seropositive children by materno-fetal transmission].

Ninety-four cases with HIV seropositive children who were found in the Hospital Necker Enfants Malades in France from April 1983 till September 1988 due to materno-fetal transmission were surveyed for immunological studies as well as the relationship between clinical symptoms and the prognosis. Lymphoadenopathy and/or hepatosplenomegaly were found in 98% of the total cases. Opportunistic infections, severe neurological problems and LIP were found in 28%, 16% and 15%, respectively. At the first laboratory examination, cases showing under 500/mm3 of OKT4 lymphocytes and with negative antigen-induced proliferative responses were observed in 24% and 44% of the cases, respectively. Negative serological profiles of antibodies to P18 and P25 HIV antigens appeared to show low values of OKT4 lymphocytes and abnormal responses to antigens. The survival cases with these findings were minimum. These data indicate that it is very much worth, while to estimate the degree of immunological deficiency and infectious complications.

CD4-Positive T-Lymphocytes↗
PubMed1989

Inherited immunodeficiency with a defect in a major histocompatibility complex class II promoter-binding protein differs in the chromatin structure of the HLA-DRA gene.

A defect in a trans-regulatory factor which controls major histocompatibility complex class II gene expression is responsible for an inherited form of immunodeficiency with a lack of expression of human leukocyte antigen (HLA) class II antigens. We have recently described and cloned an HLA class II promoter DNA-binding protein, RF-X, present in normal B cells and absent in these class II-deficient regulatory mutants. Here we report that these in vitro results correlate with a specific change in the chromatin structure of the class II promoter: two prominent DNase I-hypersensitive sites were identified in the promoter of the HLA-DRA gene in normal B lymphocytes and found to be absent in the class II-deficient mutant cells. The same two prominent DNase I-hypersensitive sites were observed in normal fibroblastic cells induced by gamma interferon to express class II genes. Interestingly, they were also observed in the uninduced class II-negative fibroblastic cells, which have also been shown to have a normal RF-X binding pattern. We conclude that the two DNase I-hypersensitive sites in the HLA-DRA promoter reflect features in chromatin structure which correlate with the binding of the trans-acting factor RF-X and which are necessary but not sufficient for the expression of class II genes.

B-Lymphocytes↗