Israel's ban on Ethiopians' blood.
Explore the source record for details and available documents.
Blood Donors↗
Biomedical subjects
A Fischer
Publications and source records attributed to A Fischer.
Deficient peptide loading and MHC class II endosomal sorting in a human genetic immunodeficiency disease: the Chediak-Higashi syndrome.
The Chediak-Higashi syndrome (CHS) is a human recessive autosomal disease caused by mutations in a single gene encoding a protein of unknown function, called lysosomal-trafficking regulator. All cells in CHS patients bear enlarged lysosomes. In addition, T- and natural killer cell cytotoxicity is defective in these patients, causing severe immunodeficiencies. We have analyzed major histocompatibility complex class II functions and intracellular transport in Epstein Barr Virus-transformed B cells from CHS patients. Peptide loading onto major histocompatibility complex class II molecules and antigen presentation are strongly delayed these cells. A detailed electron microscopy analysis of endocytic compartments revealed that only lysosomal multilaminar compartments are enlarged (reaching 1-2 micron), whereas late multivesicular endosomes have normal size and morphology. In contrast to giant multilaminar compartments that bear most of the usual lysosomal markers in these cells (HLA-DR, HLA-DM, Lamp-1, CD63, etc.), multivesicular late endosomes displayed reduced levels of all these molecules, suggesting a defect in transport from the trans-Golgi network and/or early endosomes into late multivesicular endosomes. Further insight into a possible mechanism of this transport defect came from immunolocalizing the lysosomal trafficking regulator protein, as antibodies directed to a peptide from its COOH terminal domain decorated punctated structures partially aligned along microtubules. These results suggest that the product of the Lyst gene is required for sorting endosomal resident proteins into late multivesicular endosomes by a mechanism involving microtubules.
Amino Acid Sequence↗
Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency.
In humans, interferon gamma (IFN-gamma) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas. Interleukin-12 (IL-12) receptor deficiency was found in otherwise healthy individuals with mycobacterial infections. Mature granulomas were seen, surrounded by T cells and centered with epithelioid and multinucleated giant cells, yet reduced IFN-gamma concentrations were found to be secreted by activated natural killer and T cells. Thus, IL-12-dependent IFN-gamma secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12-independent IFN-gamma secretion.
Animals↗
Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients.
We have performed a retrospective analysis of the development of T- and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixteen of 193 patients were alive with evidence of engraftment 6 months after BMT. Development of T-cell function occurred earlier than B-cell function and was achieved more frequently up to the time of last follow-up. The median time to achieve normal T-cell function was 8.7 months, whereas the median time to achieve normal B-cell function was 14.9 months. Twenty-four patients died later than 6 months post-BMT, mainly due to chronic graft-versus-host disease (cGVHD) and/or viral infection. Absence of T-cell reconstitution 6 months after BMT, unlike absence of B-cell reconstitution, was associated with a poor outcome. Two additional factors were associated with a poor outcome: presence of cGVHD 6 months after BMT and B- SCID versus B+ SCID. However, two of these three factors remained as significant prognostic factors in a multivariate analysis: the absence of T-cell function and the presence of cGVHD 6 months after BMT. Analysis of the factors influencing the development of immune reconstitution showed that T- and B-cell functions occurred earlier and more frequently in B+ SCID versus B- SCID patients. Acute GVHD was associated with a slower development of T-cell function at 6 months, and cGVHD had a negative influence on the development of T-cell function afterwards, but neither acute nor chronic GVHD was found to influence the development of B-cell function. Once engraftment occurred, whether patients had or had not received Busulfan in the conditioning regimen did not influence the kinetics and quality of T-cell function development. In a multivariate study, two factors were found to influence the T-cell function 6 months after BMT: type of SCID and acute GVHD. The results of this retrospective analysis should lead to new protocols adapted to SCID disease, considering that disease-related as well as BMT-related parameters influence the development of immune function and thereby long-term outcome after HLA-nonidentical T-cell-depleted BMT.
B-Lymphocytes↗
Evidence for an esophageal origin of VIP-IR and NO synthase-IR nerves innervating the guinea pig trachealis: a retrograde neuronal tracing and immunohistochemical analysis.
Nonadrenergic noncholinergic (NANC) relaxations of the guinea pig trachea are thought to be mediated by vasoactive intestinal peptide (VIP) and nitric oxide (NO). Physiological studies have indicated that the parasympathetic ganglion neurons mediating NANC relaxations of the guinea pig trachea but not the ganglion neurons mediating cholinergic contractions are in some way associated with the adjacent esophagus. In the present study, we attempted to locate precisely the noncholinergic parasympathetic ganglia innervating the trachealis. Two days after injection of the retrograde neuronal tracer DiI into the trachealis of organotypic cultures of the guinea pig trachea and esophagus, neurons within the myenteric plexus of the esophagus or closely associated with the outer striated longitudinal muscle layers of the esophagus were labeled. Subsequent immunohistochemical analyses revealed that a majority of the retrogradely labeled neurons possessed VIP immunoreactivity (IR) or NO synthase (NOS)-IR or had VIP-IR nerve fibers associated with their cell bodies. By contrast, no labeling of esophageal neurons was seen when the tissue between the trachea and esophagus had been disrupted by blunt dissection prior to tracer injection or when the cultures were treated with the axonal transport inhibitor colchicine. The results of these experiments provide the first direct evidence that VIP-IR and NOS-IR neurons intrinsic to the guinea pig esophagus project axons to the adjacent trachealis. Based on their location and phenotype and the results of our previous studies, it is likely that these neurons are the postganglionic parasympathetic neurons mediating NANC relaxations of the trachealis.
Animals↗
Natural and engineered disorders of lymphocyte development.
Mammals have evolved complex developmental pathways to generate a large repertoire of B and T lymphocytes capable of mounting effective immune responses. Analysis of natural and engineered immunodeficiencies constitutes a powerful approach to delineating these pathways and identifying the molecular sensors that couple the survival of developing lymphocytes to the achievement of successful gene rearrangements at the loci coding for B and T cell antigen receptors. Besides identifying cytokines, growth factors, and transcription factors involved in lymphocyte development, genetic analysis also makes it possible to organize most of these protagonists into gene networks that control critical events in the life of developing lymphocytes.
Animals↗
Ligands of CD4 inhibit the association of phospholipase Cgamma1 with phosphoinositide 3 kinase in T cells: regulation of this association by the phosphoinositide 3 kinase activity.
We have previously shown that CD4 ligands inhibit interleukin-2 (IL-2) production and T cell proliferation in human peripheral CD4+ T lymphocytes, in an MHC-independent way. Two major pathways implicated in T cell activation are inhibited by binding of CD4 ligands to the CD4 molecule, i.e. Ca2+ signaling by phospholipase Cgamma1 (PLCgamma1), and ERK-2 activation, suggesting a p21ras inhibition. We have correlated these inhibitions with the disruption of multifunctional complexes containing PLCgamma1, p120GAP and Sam68, induced by T cell activation. We report here that T cell activation through the TCR/CD3 induces an association of the phosphoinositide 3 kinase (PI3 kinase) with PLCgamma1, both in peripheral CD4+ T lymphocytes and the HUT-78 CD4+ T cell line. PI3 kinase is present in the multifunctional complexes that we have described previously. Preincubation of human peripheral CD4+ T cells and HUT-78 CD4+ T cells with gp160 or a peptide analogue of the HLA class II DR molecule precludes the association of PLCgamma1 with PI3 kinase. We also demonstrate, using two specific inhibitors of PI3 kinase activity (LY294002 and wortmannin), that this activity plays a key role in the association of PLCgamma1 with PI3 kinase. Moreover, we demonstrate the implication of the PI3 kinase activity in the negative signal mediated by HIV gp160 binding to CD4 molecules. We propose that the products of the PI3 kinase are important mediators of the negative signaling induced by the binding of CD4 ligands to the CD4 molecule implicated in the regulation of the formation of multifunctional complexes.
Amino Acid Sequence↗
Normal CD40-mediated activation of monocytes and dendritic cells from patients with hyper-IgM syndrome due to a CD40 pathway defect in B cells.
Patients with X-linked hyper-IgM syndrome [CD40 ligand (CD40L) deficiency] are prone to infections by intracellular parasites. It has been suggested that this susceptibility is caused by defective macrophage activation through the CD40L-CD40 pathway. We studied the CD40-mediated activation of monocytes and dendritic cells from patients affected with a CD40L+ hyper-IgM syndrome characterized by a defect of B lymphocyte responses to CD40 agonists. We show that the CD40-induced production of IL-6, IL-8 and TNF-alpha by monocytes, and IL-12 by dendritic cells, and expression of the activation markers CD83, the costimulatory molecules CD86 and CD80, and HLA-DR antigens were all similar in patient and control cells. This observation is consistent with the clinical characteristics of the syndrome: a defect of immunoglobulin switch but no susceptibility to opportunistic infections, as observed in CD40L-deficient patients. These observations suggest that CD40-mediated activation pathways could be, at least in part, different in B and monocytic/dendritic cell lineages.
Antigens, CD↗
Incidence and prognostic value of electrocardiographic abnormalities after heart transplantation.
BACKGROUND: The improvement of surgical techniques and the use of immunosuppressive drugs within the past 15 years has made heart transplantation an increasingly performed procedure and an accepted treatment for end-stage cardiac failure. HYPOTHESIS: The aim of this study was to describe the changes of the 12-lead electrocardiogram (ECG) after heart transplantation and to determine their prognostic value on complications such as rejection or graft coronary artery disease during follow-up. METHODS: The ECGs of 62 consecutive patients were analyzed for 5 years at follow-up periods of 1, 2, 3, 6 months and yearly after transplantation. RESULTS: The most prevalent abnormality was the presence of complete or incomplete right bundle-branch block (RBBB). New RBBB appeared in 69% (43/62) of the patients, mainly during the first month (21/43). There was no left bundle-branch block. We detected nine episodes of supraventricular arrhythmias: one atrial fibrillation, six atrial flutter, one junctional tachycardia, one orthodromic tachycardia on a Wolff-Parkinson-White syndrome; all appearing during the first 3 months. Three of the six episodes of atrial flutter occurred during an episode of acute rejection. There was no relation between RBBB and the gender and age of recipients and donors, nor with the graft ischemic time and the pretransplantation hemodynamic values. Right bundle-branch block was not associated with acute rejection nor with graft coronary artery disease. CONCLUSION: The ECG abnormalities after heart transplantation have no predictive value on the long-term evolution. Right bundle-branch block is very frequent and is not associated with adverse prognosis.
Adult↗
Clinical effects of mutations to CD95 (Fas): relevance to autoimmunity?
Explore the source record for details and available documents.
Animals↗
Stem cell transplantation for immunodeficiency.
Explore the source record for details and available documents.
Bone Marrow Transplantation↗
Anticipation of and adjustment to retirement.
The role of anticipation of retirement was studied by comparing two samples under different conditions: in the West German sample, retirement could be anticipated as "normal" with regard to the economic changes in most industrial societies between 1992 and 1994, whereas the members of the East German sample were faced with mandatory retirement, with few changes in the anticipation of this event. Findings confirm the hypotheses regarding a more negative view of retirement, different ways of coping with retirement, and equal status of cognitive functioning and health. They did not confirm the hypothesis of a lower degree of well-being in the East.
Adaptation, Psychological↗
Spiral CT aortography: an efficient technique for the diagnosis of traumatic aortic injury.
The objective of this study was to assess the efficiency of spiral CT (SCT) aortography for diagnosing acute aortic lesions in blunt thoracic trauma patients. Between October 1992 and June 1997, 487 SCT scans of the chest were performed on blunt thoracic trauma patients. To assess aortic injury, the following SCT criteria were considered: hemomediastinum, peri-aortic hematoma, irregular aspect of the aortic wall, aortic pseudodiverticulum, intimal flap and traumatic dissection. Aortic injury was diagnosed on 14 SCT examinations (2.9 %), five of the patients having had an additional digital aortography that confirmed the aortic trauma. Twelve subjects underwent surgical repair of the thoracic aorta, which in all but one case confirmed the aortic injury. Two patients died before surgery from severe brain lesions. The aortic blunt lesions were confirmed at autopsy. According to the follow-up of the other 473 patients, we are aware of no false-negative SCT examination. Our limited series shows a sensitivity of 100 % and specificity of 99.8 % of SCT aortography in the diagnosis of aortic injury. It is concluded that SCT aortagraphy is an accurate diagnostic method for the assessment of aortic injury in blunt thoracic trauma patients.
Accidental Falls↗
Risk factors for suicides of inpatients with depressive psychoses.
Research on identifying the relevant risk factors for suicides is faced with a multitude of methodological problems. The present study attempts to improve on some of these problems and to isolate those risk factors that are accessible in the early stages of the treatment of inpatients. A total of 3792 inpatients with monopolar or bipolar depression were treated during the period 1981-1992. Suicides (n=33) and controls (n=3759) were compared with respect to 77 sociodemographic and anamnestic variables and 195 standardised items of the admission summary. In addition to an analysis of contingency tables a discriminant analysis was performed. The suicide rate of patients with depressive psychosis was 2.7 times higher than the average rate of 0.324% for the entire clinic. Suicidal tendencies on admission proved to be the best predictor with a frequency of 91% in the suicide group and 40% in the control group, previous attempted suicide being the second best predictor. We conclude that the rate of inpatient suicide may have been underestimated for methodological reasons in the past decades. Many of the risk factors discussed in the literature may be of little predictive value at least in the initial stages of hospital treatment.
Adult↗
[Prevention of intestinal allograft rejection by anti-adhesion molecule antibodies in a mouse model].
STUDY AIM: Small bowel transplantation is still hampered by a high morbidity and mortality linked to the heavy non specific immunosuppression which is required by the transplantation of this lymphoid organ. Adhesion molecules appear to be potential targets for specific immunosuppression. The aim of the study was to investigate the effect of a transitory administration of anti-LFA-1 or anti-alpha 4 monoclonal antibodies (mAb) in the prevention of rejection in a model of fetal small-bowel transplantation in mice. MATERIALS AND METHODS: The small bowel of C57BL/6 (H-2b) fetus (16 to 20 days of gestation) was transplanted into adult C3H/He mice (H-2k) or C57BL/6 recipient mice. Recipients were treated with a short course of either anti-LFA-1 mAb alone, either with anti-alpha 4 mAb alone, or with both mAb. Biopsies with histological study of the grafts were performed between post-operative day 5 and 60. A score of development and rejection was assigned to each sample. RESULTS: Normal intestinal development with no sign of rejection was observed in 24/28 syngenic grafts till post-operative day 45. In the absence of treatment, intense rejection was observed as soon as day 5 and all allogenic grafts were rejected (n = 22). In contrast, in anti-LFA-1 mAb treated mice, 18/20 allogenic grafts developed normally with minimal signs of rejection. In anti-alpha 4 treated mice, a transient protective effect on small bowel allograft survival was observed on day 7 but thereafter, all grafts were massively rejected within a few days (n = 18). The combination of both mAb didn't improve the survival of the grafts when compared to anti-LFA-1 mAb treated grafts (n = 10). CONCLUSION: These results demonstrate that a transitory administration of anti-LFA-1 mAb, but not of anti-alpha 4 mAb, is able to prolong significantly the survival of non vascularized small bowel fetal grafts in mice. Our results are promising for the possible use of the anti-LFA-1 mAb in clinical intestinal transplantation.
Animals↗
The protein tyrosine kinase p60c-Src is not implicated in the pathogenesis of the human autosomal recessive form of osteopetrosis: a study of 13 children.
Osteopetrosis has been described in mice generated by homozygous gene disruption of c-src gene encoding for the p60c-Src protein tyrosine kinase (Src-/- mice). The similarities of bone histologic findings in this murine model to those observed in some patients first seen with autosomal recessive osteopetrosis, "malignant" osteopetrosis, led us to investigate the potential role of p60c-Src in the pathogenesis of malignant osteopetrosis in 13 children. In 4 patients a c-src mutation was ruled out by an intragenic microsatellite segregation study. In the other 9 we analyzed p60c-Src expression and function, as well as c-src sequence. The expression was normal in all of the patients tested. In addition, the tyrosine phosphorylation and kinase activity of p60c-Src were also normal in all of the patients. Moreover, in these patients, sequences of the coding region of c-src were identical to the published sequence of the human c-src complementary DNA. These results exclude a role for c-src in the pathogenesis of human malignant osteopetrosis in the 13 patients analyzed.
Antibodies, Monoclonal↗
Bone marrow transplantation in metachromatic leukodystrophy caused by saposin-B deficiency: a case report with a 3-year follow-up period.
A 2-year-old child had a metachromatic leukodystrophy-variant phenotype mainly involving the peripheral nervous system (PNS) that was caused by saposin-B deficiency. Bone marrow transplantation resulted in transient deterioration then continuous improvement of PNS functions. These findings were supported by nerve conduction velocity measurements, but the symptoms ultimately worsened. Magnetic resonance imaging showed persistent white matter lesions and progressive pontocerebellar atrophy.
Bone Marrow Transplantation↗
Severe aplastic anemia of neonatal onset: a single-center retrospective study of six children.
We report severe aplastic anemia of neonatal onset diagnosed in six girls between 1985 and 1995 in a single center. Initial blood cell counts (mean age 3.8 days old, 1 to 15 days) showed thrombocytopenia (six of six), anemia (four of six), and neutropenia (two of six). Neutrophil counts gradually decreased below 0.5 x 10(9)/L, and severe aplastic anemia occurred in three patients by 3 months of age and in all patients by 1 year of age. Lymphocyte number and functions were normal. In all children bone marrow biopsy showed hypocellularity for age and absence of fibrosis, blasts, lymphocytic infiltrates, and cytologic abnormalities. Blood and medullary cytogenetic studies were normal. A search for known constitutional, viral, or toxic causes was negative. Immunosuppressive therapy failed to restore hematopoiesis (three of six). Five children received a bone marrow transplantation at an average age of 9 months (range 2.7 to 29 months). One child is alive and well after a human leukocyte antigen-identical bone marrow transplantation, whereas the other four died. Both congenital onset and the high rate of familial involvement suggest that this condition may be inherited.
Anemia, Aplastic↗