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Biomedical subjects

A Blancher

Publications and source records attributed to A Blancher.

85 records · Page 5Linked to original sources
PubMed1989

Interferons and multiple sclerosis.

Interferons (IFNs) are a family of proteins with antiviral, antitumoral and immunomodulating properties. Multiple Sclerosis (MS) is a CNS disease in which the immune reaction (IR) is the cause of the inflammatory demyelinating lesions. IFNs have been demonstrated in active lesions. The location of IFN gamma on astrocytes suggests an enhancing activity on IR by inducing Ia antigen expression on these cells. In contrast, IFN alpha/beta located on microglial cells and astrocytes might limit the growing lesion. MS patients frequently present a defective response of NK cell activity and an abnormally low production of IFNs reflecting immune dysregulation. The therapeutic trials available to date are discussed: IFN gamma possesses a severe deleterious effect but IFN alpha/beta are still under consideration due to a possible beneficial activity.

Humans↗
PubMed1989

Natural autoantibodies in nude and normal outbred (Swiss) and inbred (BALB/c) mice.

Spleen cells from adult unprimed outbred (Swiss) and inbred (BALB/c) mice, either normal (no) or athymic-nude (nu) as well as spleen cells from Swiss nude mice bearing two different human tumors (BUR and PINQ), were fused with the mouse non-secreting myeloma cell line P3X63 Ag8-653. The supernatants of immunoglobulin secreting hybrids, all containing IgM, were screened for antibody activity against macromolecular antigens (autologous: actin, tubulin, myosin, dsDNA) and haptens (TNP, NP, NIP and NBrP). Furthermore, their idiotypic determinants were analyzed using a rabbit anti-idiotype which recognizes a major cross-reactive idiotype (IdD23) of BALB/c natural polyreactive autoantibodies. In all the mice studied, we identified: (1) hybrids reacting strongly with one or more haptens (10.7 to 37.8%) and (2) hybrids secreting natural monoclonal autoantibodies (NMoAb) with broad reactivities (polyreactive and/or oligoreactive) against autoantigens and/or haptens (11.4 to 26.8%). The results indicate that: (1) cells secreting natural autoantibodies with broad reactivities exist in both normal and nude mice, independently of the genetic background (inbred/outbred) of the mouse. However, in nude mice, the natural autoantibodies exhibit a more restricted pattern of reactivity (oligoreactive) compared to those of normal mice, and do not express the common idiotype IdD23 of natural polyreactive autoantibodies. (2) Tumors grafted into nude mice seem to induce the expression of polyreactive autoantibodies bearing the IdD23.

Animals↗
PubMed1989

Human monoclonal autoantibodies produced by hybridomas derived from lymphocytes of multiple sclerosis patients.

The aim of this study was to characterize autoantibodies produced in vitro by peripheral blood lymphocytes (PBL) of patients affected with multiple sclerosis (MS). We studied supernatants from man-mouse hybridomas established by fusion of PBL from 6 MS patients (group I) and from 13 individuals free of any neurological pathology (group II) with the mouse myeloma cell line P3X63 Ag8-653. They were screened for human IgG or IgM production by ELISA. Autoantibody activity against lymphocytes was studied by cell-binding ELISA. Anti-tissue reactivity was assessed by indirect immunofluorescence assay (IFA) on human cerebellum and peripheral nerve as well as on a panel of 8 non-nervous tissues. Additional ELISA tests were performed on 4 purified cellular antigens. Among 522 supernatants in group I, 13.7% contained Ig, mainly IgM, as compared to 25% among 1212 supernatants in group II; 8.3% in group I and 6.7% in group II contained anti-tissue autoantibodies. Antibodies against purified cellular antigens were found in 6% of the supernatants in group II versus 7% in group II. One human monoclonal anti-astrocyte antibody from group I was further studied. This IgM lambda (SAN-7) was particularly polyreactive and recognized glial fibrillar acid protein and other intermediate filaments, as well as tubulin and myosin. Moreover, cross-reactivity was observed with a hapten (TNP-BSA).

Antibodies, Monoclonal↗
PubMed1989

Characterization of an IgG2, G2m(23) anti-Rh-D antibody.

IgG2, G2m(23) anti-Rh-D antibodies were detected in the serum of a donor. It has been characterized by Gm typing and the use of polyclonal and mouse monoclonal anti-IgG subclasses (which had proved to be satisfactory for agglutination of sensitized red blood cells). This anti-D constitutes a good reagent for G2m(23) typing.

Antibodies, Monoclonal↗
PubMed1987

Production of monoclonal antibodies using spleen cells from nude mice bearing human tumors.

Monoclonal antibodies were generated with spleen cells from nude mice bearing human tumors. Three grafted tumors were selected because of their difference in metastatic ability in nude mice. Two were non-metastasizing carcinomas and one a highly metastasizing adenocarcinoma of the lung (Bur-tumor). Two normal nude mice were used as controls. Culture supernatants were screened by immunoperoxidase using frozen sections from both the immunizing human tumor and normal human tonsil to detect unexpected monoclonal antibodies. Two kinds of monoclonal antibodies were obtained. The first were directed against miscellaneous membrane and/or cytoplasmic antigens expressed by normal cells (e.g. normal tonsillar epithelium). Most of these antibodies corresponded to auto-antibodies and their frequency did not appear to be influenced by the fact that the mice were with or without grafted human tumors. The second type of antibodies were directed against tumor-associated antigen and generated only by fusing splenocytes from nude mice bearing the metastasizing lung adenocarcinoma. On frozen sections Bur-1-anti-tumor antibody stained all but one lung carcinoma. Occasional carcinomas originating from other organs such as pancreas and breast were also labelled. On the other hand, more than half of the cases of so-called "malignant histiocytosis" (Ki-1 lymphoma) seemed to express this epithelial antigen. Some normal cells in the lung, pancreas (acini), and kidney (distal tubules) also bound Bur-1 antibody. These results suggested that Bur-1 antibody could be related to some antibodies already described, directed against epithelial membrane antigens. When Bur-tumor was analysed by immunoblotting with Bur-1 antibody a positive reaction was obtained with material migrating in the kD-45kD molecular-weight region.

Adenocarcinoma↗
PubMed1986

[Radiologic examination of anorectal malformations].

The aim of the radiological exploration of an infant born with an ano-rectal malformation is the definition of the level and the type of the anomaly. At first a lateral abdominal roentgenogram is performed in an head-down position. The relation of the rectal cul-de-sac to the levator ani muscles is determined by its relation to the bony landmarks of the pelvis as reported by Stephens and Cremin. A real time perineal sonography is a useful complement, and permits the recognition of the same landmarks sought for by X-Ray. The research of a perineal or urinary fistula is performed at that time. In a second time, the research of associated malformations, mainly vertebral and urinary, is done.

Anal Canal↗
PubMed1983

[Production of human antitetanus antibodies by hybridomas].

Peripheral blood lymphocytes from healthy people recently immunized against tetanus toxoid (TT) were fused with human malignant B-cell lines or mouse myeloma cells (X63 Ag8.653) in an attempt to establish stable B cell hybridomas secreting anti TT antibodies. Human-human fusion experiments were not successful. In contrast, the five heterospecific fusion experiments yielded between 60 and 100% of wells that contained growing hybrids. Five of these hybrids repeatedly secreted anti-TT antibodies. One of the hybrids was cloned and secreted 10-20 micrograms/ml of human IgM, lambda anti-TT antibody. Heterospecific hybridization thus appears as an interesting method to obtain human monoclonal antibodies, allowing the study of their properties.

Animals↗
PubMedDate not supplied

Comparative study of natural autoantibodies in the serum and cerebrospinal fluid of normal individuals and patients with multiple sclerosis and other neurological diseases.

Using a panel of antigens (actin, myosin, tubulin, albumin, transferrin, peroxidase, thyroglobulin, DNA, prolactin, TNP and myelin basic protein (MBP], we have tested the antibody activity of serum and cerebrospinal fluid (CSF) from healthy individuals, patients with multiple sclerosis (MS) and individuals with other neurological diseases. No differences in the concentrations and specificities of the serum antibodies were observed among the 3 groups. In contrast, we found that MS patients often had elevated CSF antibody levels against many antigens of the panel. The MS patients with local immunoglobulin production in the central nervous system (CNS) had the highest antibody levels. Restricted antibody activity against a given antigen of the panel was not observed. Compared to the two other groups, the MS group had equivalent titres of anti-MBP antibodies in the CSF. These results suggest that, in MS, a general immune dysregulation exists which leads to a local expansion of B lymphocytes producing autoantibodies with reactivities similar to those of serum natural autoantibodies.

Antibody Specificity↗
PubMedDate not supplied

Evolution of RH genes in hominoids: characterization of a gorilla RHCE-like gene.

The human RH locus is responsible for the expression of the Rh blood group antigens. It consists of two closely linked genes, RHD and RHCE, that exhibit 92% similarity between coding regions. These observations suggest that they are derived from a relatively recent duplication event. Previously a study of nonhuman primate RH-like genes demonstrated that ancestral RH gene duplication occurred in the common ancestor of man, chimpanzees and gorillas. By amplification of intron 3 and intron 4 of gorilla RH-like genes, we have now shown that, like man, gorillas possess two types of RH intron 3 (RHCE intron 3 being 289 bp longer than the RHD intron 3) and two types of intron 4 (RHCE intron 4 being 654 bp longer than the RHD intron 4). Here we report the characterization of a cDNA encoded by a gorilla RH-like gene which possesses introns 3 and 4 of the RHCE type. A comparison of this gorilla RHCE-like coding sequence with previously characterized human and ape cDNA sequences suggests that RH genes experienced complex recombination events after duplication in the common ancestor of humans, chimpanzees and gorillas.

Amino Acid Sequence↗
PubMedDate not supplied

Local immunotherapy of recurrent glioblastoma multiforme by intracerebral perfusion of interleukin-2 and LAK cells.

A non randomized pilot study has been undertaken to evaluate the feasibility of local immunotherapy (IT) of recurrent glioblastoma multiforme (GM) by continuous intracerebral perfusion of recombinant interleukin-2 (rIL-2, Eurocetus) with and without lymphokine activated killer (LAK) cells. At time of surgical removal of the tumor, a catheter was implanted in the cavity left by tumor debulking allowing continuous perfusion of rIL-2. Five patients received 18 x 10(6) IU/day or rIL-2 for five days. At days 1, 3, and 5 after surgery, rIL-2 perfusion was briefly interrupted for the injection of LAK cells. Eight other patients received rIL-2 alone, either 24 x 10(6) IU/day (five patients) or 54 x 10(6) IU/day (three patients). Capillary leak syndrome, which is the main side effect of systemic infusion of rIL-2, was never observed, but local immunotherapy induced fever, confusion, and cerebral edema in all patients. Despite local IT, tumor progression was diagnosed by CT scan 4 to 12 weeks after the treatment.

Adult↗