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Biomedical subjects

M Pla

Publications and source records attributed to M Pla.

At least 19 recordsLinked to original sources
PubMed1992

Localization of the conformational alteration of MHC molecules induced by the association of mouse class I heavy chain with a xenogeneic beta 2-microglobulin.

Changes in the antigenicity of major histocompatibility complex (MHC) class I molecules resulting from the association of bovine beta 2-microglobulin (beta 2-m) with mouse class I heavy chains were investigated. Mice (H-2b) were immunized with syngeneic Concanavalin A (Con A) blasts induced in the presence of fetal calf serum (FCS) in conditions allowing exchange between mouse and bovine beta 2-microglobulin (beta 2-m). Spleen cells from hyperimmunized mice were fused with myeloma cells and two monoclonal antibodies which required for their reactivity the presence of FCS have been further studied. One of them (CAB 297) recognized a determinant of bovine beta 2-m which is present on free molecules in solution as well as when they are associated with either mouse or bovine class I heavy chains. In contrast, the second monoclonal antibody (CBB 70) did not react with free bovine beta 2-m molecules, nor with beta 2-m associated with bovine class I heavy chains. It did react with cells of some H-2 haplotypes (b, f, p and r) but only when their class I heavy chains are associated with bovine or with human beta 2-m. Therefore, expression of the CBB 70 defined antigenic determinant requires both xenogeneic beta 2-m and class I heavy chain of a given H-2 molecule. In order to precisely localize the antigenic determinant defined by this monoclonal antibody and therefore the region altered by the association of class I heavy chain with xenogeneic beta 2-m, we made use of exon shuffled class I molecules. The results indicate that changes induced by the association of bovine beta 2-m with H-2 class I heavy chain affect the conformation of the alpha 2 domain. These studies illustrate that MHC class I molecules exhibit a considerable conformational flexibility which could influence their ability to bind and present various peptides to the T-cell receptor.

Animals↗
PubMed1992

Clinical experience with a single field rotational total skin electron irradiation technique for cutaneous T-cell lymphoma.

Between October 1981 and December 1989, 44 patients with cutaneous T-cell lymphoma (CTCL) were treated with a single field rotational total skin electron irradiation (RTSEI) technique developed in the McGill University, Department of Radiation Oncology. Only 11 (25%) of the 44 patients had received no prior treatment. Three-quarters (33/44) had advanced (T3 or T4) disease. Complete responses were seen in 32/44 (73%) of patients (91% T2, 71% T3 and 58% T4), but only 3/11 (27%) of patients with T2 disease and 3/21 (14%) of patients with T3 disease remain in continuous complete remission in the skin, after median intervals of 58 and 35 months, respectively. Median cause-specific survival for the whole group is 43 months and survival at 5 years is 38%. Survival was significantly better for patients with T2 disease than for patients with T3 disease (relative risk 4.3; 95% CI 1.4-13.2) and patients with T4 disease (relative risk 3.1; 95% CI 0.8-12.1). The RTSEI technique used at McGill has depth-dose characteristics and photon contamination similar to other commonly used TSEI techniques. It is relatively simple and provides a homogenous dose distribution over the entire skin surface in a short treatment time. Results of treatment are similar to those obtained with other techniques. For T2 disease, TSEI is an effective treatment modality with a possibility of long-term tumor control. For more advanced disease, more aggressive treatment, which may include TSEI, is necessary.

Adult↗
PubMed1992

Expression of human CD4 in transgenic mice does not confer sensitivity to human immunodeficiency virus infection.

Transfection of the human CD4 molecule into mouse cells does not confer susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. Expression of the human CD4 molecule in transgenic mice was seen to offer some new possibilities. However, transgenic mouse T cells expressing either the human CD4 receptor, or a hybrid human/mouse CD4 receptor alone or in conjunction with human major histocompatibility complex class I molecules, were refractory to in vitro HIV-1 infection. In addition, no infection was observed after in vivo HIV inoculation to mice of these various transgenic lines. Injection of recombinant gp160 viral protein to the transgenic mice did not alter their T and B cell populations. The existence of a dominant block in mouse cells that prevents HIV entry is discussed.

Animals↗
PubMed1992

The interaction of two groups of murine genes determines the persistence of Theiler's virus in the central nervous system.

Theiler's murine encephalomyelitis virus is responsible for a chronic inflammatory demyelinating disease of the central nervous system of the mouse. The disease is associated with persistent viral infection of the spinal cord. Some strains of mice are susceptible to viral infection, and other strains are resistant. The effect of the genetic background of the host on viral persistence has not been thoroughly investigated. We studied the amount of viral RNA in the spinal cords of 17 inbred strains of mice and their F1 crosses with the SJL/J strain and observed a large degree of variability among strains. The pattern of viral persistence among mouse strains could be explained by the interaction of two loci. One locus is localized in the H-2D region of the major histocompatibility complex, whereas the other locus is outside this complex and is not linked to the Tcrb locus on chromosome 6.

Animals↗
PubMed1991

Fractionated stereotactic radiation therapy for intracranial tumors.

In stereotactic radio surgery, a single, large dose of radiation is delivered to a small, well-defined, stereotactically localized intracranial lesion. In contrast to conventional radiation therapy, in radio surgery no attempt is made to spare normal cells within the target volume by fractionating the tumor dose. In 1987, the authors began a program of fractionated stereotactic radiation therapy for selected tumors involving sensitive brain structures. Their objective was to improve the therapeutic index and study the feasibility of the fractionated technique. Fifteen patients were treated with a multifraction regimen typically consisting of six fractions of 700 cGy each, given on alternate days for 2 weeks (total tumor dose, 4200 cGy). All patients were treated with the dynamic stereotactic radio surgical technique. A head ring ("halo frame") was used for immobilization and setup during radiation treatments. At a median follow-up time of 27 months, the symptoms of the majority of the patients improved clinically; this improvement usually occurred within a few weeks after completion of the treatment. The radiologic response was much slower. Currently, only two patients have had complete radiologic disappearance of their lesions; the majority of the patients have only had a decrease in tumor size. The treatments were well tolerated by the patients and no acute complications were observed. One patient who had a vasogenic edema 11 months after treatment fully recovered after steroid therapy. Fractionated stereotactic radiation therapy is a feasible treatment technique and may prove to be useful for selected patients with intracranial tumors. Although the preliminary data are encouraging, this technique should still be considered experimental. A larger number of patients and a longer follow-up time are necessary to determine whether the results of this technique are actually better than those of conventional radiation therapy.

Adolescent↗
PubMed1991

Regulation of the maize rab17 gene promoter in transgenic heterologous systems.

The maize rab17 gene is expressed in different plant parts in response to ABA and osmotic stress (J. Vilardell et al., Plant Mol Biol 14 (1990) 423-432). Here we demonstrate that 5' upstream sequences of the rab17 gene confer the appropriate patterns of expression on the chloramphenicol acetyl transferase (CAT) reporter gene in transgenic tobacco plants, as well as in protoplasts derived from cultured rice cells. Specifically, a CAT construct containing a large 5' upstream fragment of rab17 (-1330/+29) results in high levels of CAT activity in embryos, leaves and roots of transgenic plants subjected to water stress or ABA treatment. Transient expression assays in rice protoplasts transfected with CAT genes fused to rab17 promoter deletions indicate that a 300 bp DNA fragment (-351/-102) is sufficient to confer ABA responsiveness upon the reporter gene. Furthermore, a 100 bp sequence (-219/-102) is capable of conferring ABA responsiveness upon a minimal promoter derived from the 35S CaMV promoter. Gel retardation experiments indicate that maize nuclear proteins bind to this fragment. This region of 100 bp contains a sequence (ACGTGGC) which has been identified as an abscisic acid response element in studies of other ABA-responsive plant genes.

Cell Nucleus↗
PubMed1991

Recognition of HLA-B27 by mouse cytotoxic T-cell clones: a transgenic mouse model.

As a basis for the characterization of mouse T cells involved in the recognition of xenogeneic HLA molecules, a panel of HLA-B27-reactive cytotoxic T-cell clones was generated upon stimulation by cells from HLA-B27-transgenic mice. The HLA-B27-induced T-cell response was found to comprise two categories of clones: some recognizing HLA-B27 independent of H-2 molecules expressed by the target cells (unrestricted clones), others recognizing HLA-B27 in an H-2-restricted manner. The unrestricted clones exhibited diverse specificities, as judged from their various cross-reactivities with other xenogeneic (HLA) or allogeneic (H-2) molecules. In addition, although most of the unrestricted clones were able to react with both mouse and human HLA-B27-transgenic mice. The HLA-B27-induced T-cell which reacted only with HLA-B27-positive mouse, and not human cells. These findings illustrate that both H-2-restricted and unrestricted T cells with diverse specificities contribute to HLA-B27-xenorecognition.

Animals↗
PubMed1991

Regulation of the abscisic acid-responsive gene rab28 in maize viviparous mutants.

We have isolated a new maize gene, rab28, that responds to abscisic acid (ABA) treatment. This gene has been characterized by determining the sequence of the cDNA and corresponding genomic copy, and by mapping the start site of its transcript. The rab 28 gene encodes a protein of predicted molecular weight 27713 Da which shows strong homology with the Lea D-34 protein identified in cotton. The proximal promoter region contains the conserved ABA-response element, CACGTGG, reported in other plant genes to be responsible for ABA induction. rab 28 mRNA has been identified as ABA-inducible in embryos and young leaves. It is also induced by water-stress in leaves of wild-type plants. Regulation of the rab 28 gene was studied in maize viviparous mutants. The results obtained with the ABA-insensitive vp1 mutant show that rab 28 transcripts do not accumulate to a significant level during embryogenesis. Surprisingly, induction of rab 28 mRNA can be achieved in young embryos by exogenous ABA treatment. Moreover, water-stressed or ABA-treated seedlings of vp1 contain significant levels of rab 28 mRNA which is not detectable in well-watered seedlings. Regulation of the rab 28 gene in excised young embryos of ABA-deficient vp2 mutants, in which influences of the maternal environment are absent, closely resembles that found in non-mutant excised young embryos. The significance of these results is discussed.

Abscisic Acid↗
PubMed1991

Physical aspects of the angle-beta concept in electron arc therapy.

A technique for the determination of treatment parameters that are required to achieve a desired depth dose distribution in electron arc therapy is discussed and a method for calculating isodose distributions is presented. Both the treatment technique and the dose calculation method rely on the angle beta concept, which uniquely describes the dependence of the radial percentage depth doses in electron arc therapy on the nominal field width, isocenter depth, and virtual source-axis distance. The angle beta concept is discussed in detail and the electron pseudo-arc therapy technique used at McGill is described. Also presented is the method used to achieve dose homogeneity in target volumes treated with the pseudo-arc technique.

Electrons↗
PubMed1991

Induction of ovulation in rabbits with pure urinary luteinizing hormone and human chorionic gonadotrophin: comparison of oocyte and embryo quality.

Thirty-six 18-week-old nulliparous does were stimulated with a single dose of 25 IU pregnant mare serum gonadotrophin (PMSG). Ovulation was induced 48 h later with 50 IU luteinizing hormone (LH) (18 does) or 50 IU human chorionic gonadotrophin (HCG) (18 does) in order to determine the effects of pure urinary LH and HCG on the quality of oocytes and embryos. Nine does were mated in each group. The does were slaughtered 24 h after induction of ovulation to recover oocytes and 48 h after mating to recover embryos. The number of haemorrhagic, preovulatory and luteinizing follicles per ovary were recorded. The quality of oocytes and embryos recovered were evaluated. No significant differences in the number of haemorrhagic follicles (blood follicles without stigma), preovulatory and luteinizing follicles were observed between LH and HCG groups. LH has a selective action, which could permit the acquisition of better quality oocytes. Although the fertilization rate was similar in both groups (LH versus HCG), the percentage of degenerate embryos (grade 5) was lower for the LH (3%) than the HCG (13%) groups.

Animals↗
PubMed1991

Analysis of primary HLA-specific cytotoxic T cell response in graft-draining lymph nodes--a transgenic mouse model for in vivo recognition of human MHC antigens.

In order to characterize primary anti-HLA cytotoxic T cells and especially those involved in graft rejection, we have utilized a transgenic mouse model. Mice (non-transgenic and HLA-transgenic) were grafted with spleen cells originating from H-2-matched transgenic mice expressing HLA-B27 molecules, and cells from graft-draining lymph nodes were tested in CML assay to investigate the primary in vivo induced CTL responses. The results showed that HLA-B27 molecules were able to raise strong primary xenogeneic CTL responses. Results from split-well analysis indicated that although recognition of HLA-B27 by primary CTL induced in nontransgenic recipients is predominantly unrestricted by H-2, a small fraction (ranging from 2% to 27%) of the primary in vivo induced CTL is able to recognize HLA-B27 in an H-2-restricted manner. HLA-specific H-2-restricted CTL had never so far been demonstrated in the primary T cell response. Thus the protocol used in our study for the generation of a primary CTL response seems to provide not only a more appropriate representation of cytotoxic T cells sensitized by a graft, but also to be a more sensitive approach than the usually used in vitro mixed lymphocyte culture.

Animals↗
PubMed1991

The SCID mouse.

Numerous investigations of the mammalian hematopoietic system in normal and pathologic states have been facilitated by the study of genetically determined immunologic dysfunctions in experimental animals. This article focuses on the scid mutation of the mouse (SCID mouse) that causes severe defects in the development of the immune system. The mutation appears to impair the recombination of antigen receptor genes, causing in the SCID mice a lack of functional T and B lymphocytes. Other hematopoietic cell types appear to develop and function normally. SCID mice readily support normal lymphocyte differentiation and can be reconstituted with normal lymphocytes from syngeneic or allogeneic mice and even partially reconstituted with human lymphocytes. They also support the growth of allogeneic and xenogeneic tumors. Thus, SCID mice might be useful for studies of both normal and abnormal lymphocyte development and function.

Animals↗
PubMed1990

Dynamic stereotactic radiosurgery in arteriovenous malformation. Preliminary treatment results.

From December 1986 through August 1988, 25 patients with intracranial arteriovenous malformations underwent radiosurgery with the dynamic stereotactic irradiation technique. The prescribed dose at isocenter ranged from 50 Gy to 55 Gy, given as a single fraction in 92% of the patients. Field sizes, defined at the 90% isodose surface, varied from 5 mm to 25 mm and were chosen in order to deliver 20 to 25 Gy at the periphery of the malformation. To date, 14 angiographic studies were repeated at 1 year posttreatment. In six patients (43%) a complete obliteration of the lesion was achieved. Late side effects were observed in three patients. Our initial analysis, at 1 year posttreatment, suggests that our results are comparable with those previously reported for other radiosurgical techniques. The linac-based dynamic stereotactic technique appears to be a valid alternative to radiosurgery with the Gamma unit or with heavy-charged particle beams.

Adolescent↗
PubMed1990

Radiosurgery with photon beams: physical aspects and adequacy of linear accelerators.

The question of the adequacy of isocentric linear accelerators (linacs) for use in radiosurgery is addressed. The general physical requirements for radiosurgery, mainly a high spatial and numerical accuracy of dose delivery, reasonable treatment time, and low skin and leakage dose as well as cost considerations are examined. Various linac-based procedures are analyzed in view of their ability to meet these requirements and are contrasted with the clinically proven system of the Gamma unit. It is shown that the linac-based multiple converging arcs techniques and the dynamic rotation meet the stringent physical requirements on dose delivery and are thus viable alternatives to radiosurgery with the commercially available and dedicated Gamma unit.

Costs and Cost Analysis↗
PubMed1990

Radiosurgery of cerebral arteriovenous malformations with the dynamic stereotactic irradiation.

From December 1986 through December 1988, 33 patients with inoperable arteriovenous malformation (AVM) were treated in our center with the dynamic stereotactic radiosurgery, which uses a standard 10 MV isocentric linear accelerator. There were 18 females and 15 males with a median age of 26 years (range: 9-69) and a median follow-up time of 16 months (range: 7-32). The arteriovenous malformation volumes treated ranged from 0.2 to 42 cm3. The prescribed doses at the isocenter varied from 50 to 55 Gy and were given as a single fraction in the majority of the patients (31/33). Late complications consisting of intracranial bleeding and/or hemiparesis were observed in three patients. To date, 21 patients underwent repeat angiographic studies at 1 year post-treatment. A complete obliteration of the lesion was achieved in 38% of these patients. For the patients whose arteriovenous malformation nidus was covered by a minimum dose of 25 Gy, the total obliteration rate was 61.5% (8/13), whereas none of the patients who had received less than 25 Gy at the edge of the nidus obtained a total obliteration. Our preliminary analysis at 1 year post-radiosurgery reveals results comparable to those previously reported for other radiosurgical techniques for the same follow-up period.

Adolescent↗
PubMed1990

HLA- and H-2-associated variations of intra- and extracellular magnesium content.

Erythrocyte and plasma magnesium (EMg, PMg) levels have been shown to be genetically controlled in human and mouse. The possible association of these genetic factors with the major histocompatibility complex (MHC) (HLA and H-2) was investigated. Among unrelated adult male blood donors, HLA-B35 carriers have PMg (P less than 0.01) and EMg (P less than 0.0005) levels lower than those of noncarriers, while HLA-B38 carriers exhibit a significant (P less than 0.05) increase of both PMg and EMg levels when compared to the other individuals. Furthermore, HLA identical sibs have EMg values more similar than those of HLA different sibs. In the mouse, erythrocyte (P less than 0.001), plasma (P less than 0.001), liver (P less than 0.03), and spleen (P less than 0.04) Mg contents vary significantly according to H-2, with higher values being found in H-2k than in H-2q or H-2b congenic strains. However, non-MHC genes also have an influence on erythrocyte (P less than 10(-10], plasma (P less than 10(-10], spleen (P less than 10(-5], and kidney (P less than 10(-6] Mg contents as shown by differences between H-2 identical strains, which differ by the C3H and B10 genetic backgrounds. In conclusion, genetic factors controlling intra- and extracellular Mg levels are composed of at least three components: MHC (HLA and H-2)-associated genes, non-MHC genes, and tissue factors modulating the respective importance of the first two sets of factors. The mechanisms underlying this genetic system are discussed.

Adult↗