Mandibular effects of maxillary distraction osteogenesis in cleft lip and palate.

Maxillary distraction osteogenesis (DO) is a reliable treatment for severe maxillary deficiency in cleft lip and palate (CLP). The objective was to analyze its long-term effects on the mandible. A retrospective study of 24 CLP treated with maxillary DO using the Polley and Figueroa technique was done; patients were followed for more than 4 years. Preoperative (T0), 6-12 months postoperative (T1), and ≥ 4 years postoperative (T2) cephalometric radiographs were evaluated. A classical cephalometric analysis was used to assess treatment stability, and a Procrustes superimposition method was used to assess local changes in the shape of the mandible. The mean age of patients at T0 was 15.4 ± 4.1 years. SNA increased at T1 and T2 (P < 0.001), with no significant relapse between T1 and T2, indicating stability at 1 year after treatment (T0 = 72.4 ± 5.3°; T1 = 81.3 ± 6.2°; T2 = 79.9 ± 6.1°). SNB, facial angle, gonial angle, and symphyseal angle remained stable. Long-term analysis of the mandible demonstrated a minimal counter-clockwise rotation of the body (mandibular plane = -0.2 ± 3.2°) and ramus (-0.6 ± 4.3°). Maxillary DO in CLP had no significant effect on the shape or rotation of the mandible. The maxillary advancement remained stable after 1 year.

[Mandibular asymmetry in plagiocephaly without synostosis]. / Etude de l'asymétrie mandibulaire dans les plagiocéphalies sans synostose.

SUBJECT: The number of plagiocephalies without synostosis (PWS) strongly increased in the last decade. Its impact on the mandible remains badly understood, the more so as there are various forms of PSS. The purpose of this study was to analyze mandible deformation according to the deformation of PWS. MATERIAL AND METHODS: The study was carried out retrospectively starting from three-dimensional scans of children presenting with a PWS. They were classified in 2 groups according to the deformation of the cranium. There were 51 frontal plagiocephalies (PF) and 19 occipital plagiocephalies (PO) for which the cephalic index was calculated. The position of the mandible compared to the base of cranium and its intrinsic asymmetry were analyzed (paired parametric Student test). RESULTS: The mandible was symmetrical in PO whereas it was asymmetrical for PF. This asymmetry was present at the level of the corpus and developed in 2 ways: that is to say asymmetry compensated for that of the base of the cranium (68.6%); or it worsened it (23.5%). The degree of brachycephaly was more important in PO than the PF with a cranial index of 0.93+/-0.07 and 0.85+/-0.07 respectively (P<0.05). In both cases the position of the mandibular condyle followed the asymmetry of the base of cranium and the asymmetry of the temporomandibular joint (TMJ) was secondary with that of the base of cranium. DISCUSSION: In addition to the asymmetry of TMJ position there was an intrinsic mandibular asymmetry in PF which was not found in PO. This asymmetry of the mandible was variable but in most cases it tended to compensate for the asymmetry of the base of the cranium which was more important in PF. The risk to have asymmetry of dental occlusion seems more important in PF than in PO, and an orthodontic follow-up appeared to be justified for these children.

The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis.

Lymphomas were studied in kindreds with autoimmune lymphoproliferative syndrome (ALPS; Canale-Smith syndrome), a disorder of lymphocyte homeostasis usually associated with germline Fas mutations. Fas (CD95/APO-1) is a cell surface receptor that initiates programmed cell death, or apoptosis, of activated lymphocytes. Lymphoma phenotype was determined by immunohistochemistry, frequency of CD3(+)CD4(-)CD8(-) T-cell-receptor alpha/beta cells by flow cytometry, nucleotide sequences of the gene encoding Fas (APT1, TNFRSF6), and the percentage of lymphocytes undergoing apoptosis in vitro. Of 223 members of 39 families, 130 individuals possessed heterozygous germline Fas mutations. Eleven B-cell and T-cell lymphomas of diverse types developed in 10 individuals with mutations in 8 families, up to 48 years after lymphoproliferation was first documented. Their risk of non-Hodgkin and Hodgkin lymphomas, respectively, was 14 and 51 times greater than expected (each P <.001). Investigation of these 10 patients and their relatives with Fas mutations revealed that all had defective lymphocyte apoptosis and most had other features of ALPS. The tumor cells retained the heterozygous Fas mutations found in the peripheral blood and manifested defective Fas-mediated killing. These data implicate a role for Fas-mediated apoptosis in preventing B-cell and T-cell lymphomas. Inherited defects in receptor-mediated lymphocyte apoptosis represent a newly appreciated risk factor for lymphomas.

Growth regulation of activated lymphocytes: defects in homeostasis lead to autoimmunity and/or lymphoma.

Homeostasis within the immune system is complicated by the need to selectively force the survival of potentially useful lymphocytes in the central lymphoid organs and of antigen-reactive cells in the periphery. Coupled with this requirement, is the need to delete strongly autoreactive cells in the thymus and bone marrow and downsize the foreign antigen-reactive cells following elimination of the pathogen. Homeostasis is achieved by coupling the fate of the cell to the integration of signals received through the antigen receptor, co-stimulatory receptors and cytokine receptors as well as members of the tumor necrosis factor receptor family that are highly specialized to promote survival or death of a cell. In this review, we briefly discuss how well-defined pathways that promote cell survival PI-3 kinase, Akt, Bcl-2 family and inhibitors of apoptosis (IAPs)-function within the cell. We discuss how cell death stimuli signal either the intrinsic, mitochondrial pathway of apoptosis or kill the cell through one of the six death receptors such as Fas (APO-1/CD95). Finally, the consequences of spontaneous and genetically engineered mutations within survival and death pathways are discussed in the context of predisposition to autoimmune disease and cancer.

Activation of the CD95 system increases with disease progression in human immunodeficiency virus type 1-infected children and adolescents.

BACKGROUND: Increased apoptosis in infected as well as noninfected cells has been invoked in CD4+ T helper cell depletion during HIV-1 infection. A strong increase in the expression of CD95 (APO-1/Fas) and CD95 ligand, key regulators of apoptosis in normal T cells, has previously been described in freshly isolated T cells from HIV-1-positive children when compared with healthy age-matched controls. We also found an increase in spontaneous as well as specific CD95-mediated apoptosis in CD4+ and CD8+ T cells from these patients. However, the relationship of these findings to disease progression in children with HIV infection is not known. MEASUREMENTS AND SUBJECTS: We studied expression of CD95 and CD95 ligand as well as sensitivity towards spontaneous and anti-CD95-triggered apoptosis of T cells in 33 HIV-1-positive children and adolescents in different disease stages. RESULTS: Loss of CD4+ T cells in vivo was paralleled by an increase in the percentage of CD95 high T cells and an increase in anti-CD95-induced apoptosis of CD4+ T cells. CD95L mRNA was constantly up-regulated in T cells from patients in intermediate disease stages whereas patients with normal CD4 counts and patients with advanced T cell loss showed CD95 ligand-mRNA levels in or slightly above the range of normal controls. CONCLUSIONS: Disturbed regulation of the CD95 system may play an important role in the development of immunodeficiency during the course of HIV infection in children.

Activation of the CD95 (APO-1/Fas) system in T cells from human immunodeficiency virus type-1-infected children.

Increased apoptosis of CD4+ T cells is considered to be involved in CD4+ T-cell depletion in human immunodeficiency virus type-1 (HIV-1)-infected individuals progressing toward acquired immunodeficiency syndrome (AIDS). We have recently shown that CD95 (APO-1/Fas) expression is strongly increased in T cells of HIV-1-infected children. In this report we provide further evidence for a deregulated CD95 system in AIDS. CD95 expression in HIV-1+ children is not restricted to previously activated CD45RO+ T cells but is also increased on freshly isolated naive CD45RA+ T cells. In addition, specific CD95-mediated apoptosis is enhanced in both CD4+ and CD8+ T cells. Furthermore, levels of CD95 ligand mRNA are profoundly increased. Specific T-cell receptor/CD3-triggered apoptosis in HIV-1+ children is more enhanced in CD8+ than in CD4+ T cells. Accelerated activation induced cell death of T cells could partially be inhibited by blocking anti-CD95 antibody fragments. These data suggest an involvement of the CD95 receptor/ligand system in T-cell depletion and apoptosis in AIDS and may open new avenues of rational intervention strategies.

Regulation of cell surface APO-1/Fas (CD95) ligand expression by metalloproteases.

APO-1/Fas (CD95) ligand (APO-1L) induces apoptosis in sensitive target cells. Activation-induced T cell death and Ca2(+)-independent cytotoxicity in perforin knockout mice are mediated by APO-1L. To define whether APO-1L is expressed on the surface of activated T cells and to investigate the mechanisms leading to the release of a soluble form, we developed rabbit anti-APO-1L antibodies (Ab). The purified rabbit Ab detected the mature forms of the human and mouse APO-1L of approximately 42 and 40 kDa. In addition, the Ab recognized the non-glycosylated form of APO-1L of approximately 32-33 kDa. In activated human T cells, the soluble form of APO-1L was detectable with a molecular mass of 26 kDa. Immunofluorescence of three human T lymphoblastoid cell lines showed that activation of these cells by phorbol 12-myristate 13-acetate/ionomycin induced a significant increase in cell surface APO-1L only in the presence of metalloprotease inhibitors. Zn2+, but not Ca2+, prevented the increase in surface APO-1L observed in the presence of 1,10-phenanthroline. Blocking of other classes of proteases (serine- and acid-proteases, chymotrypsin) had no effect. Increased expression of surface APO-1L by metalloprotease inhibitors was not dependent on T cell activation, as the metalloprotease inhibitors also modulated the low level of constitutive APO-1L expression. These results suggest that cell surface expression of human APO-1L is regulated by Zn2(+)-dependent metalloproteases. Cleavage of surface APO-1L may act as a regulatory mechanism to prevent accumulation of the membrane-bound form and may cause systemic effects of the APO-1L.

Molecular mechanisms of APO-1/Fas(CD95)-mediated apoptosis in tolerance and AIDS.

The cell surface molecule APO-1/Fas(CD95), a member of the Tumor Necrosis Factor (TNF) receptor/Nerve Growth Factor (NGF) receptor superfamily mediates apoptosis upon cross-linking by agonistic antibodies or its ligand. Recent findings suggest that APO-1/Fas(CD95) and its ligand are the key molecules for antigen receptor-induced apoptosis in activated mature T cells. Here we propose a mechanism for antigen receptor-induced apoptosis of activated T cells via APO-1 ligand mediated autocrine suicide. This mechanism may also contribute to the depletion of CD4+ T cells in AIDS.

Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)

The APO-1/(Fas/CD95) cell surface receptor is a member of the nerve growth factor (NGF)/tumour necrosis factor (TNF) receptor superfamily and mediates apoptosis. Peripheral activated T cells (ATC) from lymphoproliferation (lpr/lpr) mutant mice that express a reduced number of APO-1 receptors have a defect in T-cell receptor (TCR)-induced apoptosis. This suggests that TCR-induced apoptosis involves APO-1. We tested this hypothesis in various human T cells: (1) malignant Jurkat cells, (2) an alloreactive T-cell clone (S13), and (3) peripheral ATC. TCR triggering through immobilized anti-CD3 antibodies or Staphylococcus enterotoxin B (SEB) superantigen induced expression of the APO-1 ligand and apoptosis in these cells. Anti-CD3-induced apoptosis of Jurkat cells was demonstrated even in single-cell cultures. In all cases apoptosis was substantially inhibited by blocking anti-APO-1 antibody fragments and soluble APO-1 receptor decoys. The APO-1 ligand was found in the supernatant of activated Jurkat cells as a soluble cytokine. We propose that TCR-induced apoptosis in ATC can occur through an APO-1 ligand-mediated autocrine suicide. These results provide a mechanism for suppression of the immune response and for peripheral tolerance by T-cell deletion.

[Chlamydia trachomatis--detection of inflammatory diseases of the fallopian tubes]. / Chlamydia trachomatis--Nachweis bei entzündlichen Erkrankungen der Eileiter.

The prevalence of Chlamydia trachomatis in tubal swabs obtained by laparoscopy was investigated in a prospective study. Specimens were collected from women with salpingitis (group 1), tubal infertility (group 2) and from controls, which were considered as being not infected and subjected to laparoscopy for other reasons (group 3). In the period 12/1980-8/1984 chlamydial infection was diagnosed, by means of the McCoy tissue culture method, in group 1 in 19% (16/85), in group 2 in 4% (10/250) and in group 3 in 0% (0/122). In a second period until 6/1985, positive chlamydial cultures were seen in 2% (1/44), 2% (2/110) and 0% (0/75) respectively, however, a simultaneously used IFT (Micro Trak, Syva Merck) was negative in all cases. In the third period until 12/1986, positive chlamydial cultures were obtained in 12% (9/77), 1% (1/137) and 4% (4/90) respectively. The sensitivity of a simultaneously performed EIA (Chlamydiazyme, Abbott) in women with salpingitis was 67%, the specificity was 97%. The EIA seemed to provide an alternative diagnostic method to culture when evaluating tubal specimens. In an additional trial, chlamydial complement fixation test was positive in 26% of a total of 90 women with tubal infertility (and negative tubal culture) vs. 6% in a control group of pregnant females (p less than 0.001). In conclusion, the reported results support the etiologic role of Chlamydia trachomatis as an important agent in salpingitis as well as in tubal infertility.

[Elimination of major salivary glands by temporary medicamentous occlusion of the excretory ducts (author's transl)]. / Ausschaltung von Speicheldrüsen durch temporäre Okklusion des Gangsystems mit einer Aminosäurenlösung. Tierexperimentelle Studie zu einem neuen Therapieverfahren.

The treatment of chronic recurrent inflammation of major salivary glands means reduction or elimination of parenchyma. Several operative and non-operative procedures have been described for this purpose. A new method is the instillation of an amino-acid solution which is hardening in the excretory ducts. Histological findings in experiments on animals show an atrophy of parenchyma while the filling mass is completely removed. Some patients were treated successfully by this method up to now.