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Biomedical subjects

P Calvas

Publications and source records attributed to P Calvas.

11 recordsLinked to original sources

t(9;11)(p22;q23) translocation in blastic phase of chronic myeloid leukemia.

A patient with chronic myeloid leukemia showed clonal karyotypic evolution, with the appearance of an i(17q) and t(9;11)(p22;q23). This case sheds light upon leukemogenic events related to t(9;11)(p22;q23). The presence of t(9;22) and t(9;11) in the same clone showed that t(9;11) may affect a pluripotent stem cell, thus accounting for t(9;11) in both lymphoid and monocytic leukemias. In this patient, t(9;11) could not be related to a prior cytotoxic exposure and was instead the result of natural evolution of chronic myeloid leukemia. Furthermore, this led us to assume that the phenotype of blast cells may be determined by a chromosome abnormality. A phenotypic conversion from myeloblastic to undifferentiated morphologic aspect was observed when t(9;11) was detected, suggesting that t(9;11) may have induced a loss in differentiation of blast cells affected by this change. This assumption is in agreement with the putative presence of genes activated in pluripotent progenitors by 11q23 rearrangements.

Blast Crisis

[Role and contribution of karyotyping in male infertility].

In the context of the aetiological investigation of male infertility, the authors stress the place and the contribution of blood karyotype testing in the light of their personal experience based on 1,612 subjects. This examination has an important place, as about 15% of azoospermic subjects and 6 to 7% of subjects with oligospermia less than 10 million spermatozoa per ml, either alone or in combination with other abnormalities of the semen examination, present a congenital chromosomal abnormality. A remarkable constancy of the results was observed according to identical recruitment criteria. The contribution of this examination is also important: the medical and psychological value of detecting the cause of azoospermia, genetic counselling and antenatal chromosomal diagnosis for non-azoospermic subjects with an equilibrated structural abnormality, in whom treatment allows a chance of procreation, genetic counselling for the family of these subjects in order to prevent the appearance of a chromosomally abnormal infant. In conclusion, the authors argue in favour of the routine use of this test in all infertile subjects with at least isolated oligospermia less than 10 million spermatozoa per ml.

Chromosome Aberrations

[Study of equivalents of rhesus antigens in non-human primates].

Human alloantibodies specific of some Rh antigens cross-react with non human primates red blood cells. These crossreactions demonstrated that only African apes express equivalents of Rho (D) and hr' (c). The antigenic resemblance between these two human antigens and their primate homologues is confirmed by the reactivities of human anti-D and anti-c monoclonal antibodies. The use of a human Rh cDNA probe allowed to confirm by Southern blot hybridization that nonhuman primates possess Rh-like genes. The number of Rh-like genes per haploid genome was deduced from the results obtained with exon-specific probes.

Animals

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

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

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

[Detection of triple X syndrome during a familial inquiry for hemophilia A].

In order to give a genetic counsel to the mother and the two twin-sisters of an Hemophilia A boy, a familial investigation has been carried out. The study with the restriction fragment length polymorphism probes together with the hemostasis screening enabled to specify the status of each member of the family with respect to hemophilia A gene. This investigation evidenced the presence of two maternal alleles and one paternal allele in one of the twin-sisters. This led us to assume that she had a chromosomal abnormality in spite of her normal phenotype. The 47, XX, +(X) result of her karyotype confirmed this assumption. Therefore an accurate genetic counsel was provided to the members of this family and more particularly to the triple X subject.

Female

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

[Chromosome anomalies and male infertility. A study of 1,444 subjects].

Chromosomal anomaly was detected in 7.6% of a cytogenetic survey of 1,444 infertile male azoospermia or oligozoospermia with a sperm count below 20 million/ml. Anomalies are especially of the sex-chromosome and of autosomal robertsonian translocation type. Distribution of these subjects on account of the sperm count has pointed out an increase of chromosomal anomalies in inverse ratio to the sperm count.

Chromosome Aberrations

[Partial trisomy 13 due to t(X;13) translocation. Contribution of in situ hybridization].

A new case of partial trisomy 13 through unbalanced de novo translocation t(X;13) is reported. In situ hybridization has been used to specify breakage points on the X chromosome. This case is cytogenetically comparable with another reported case; the phenotypical aspect of these two patients is however different. This discrepancy is discussed.

Chromosomes, Human, Pair 13