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A Fischer

Publications and source records attributed to A Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2004

Determination of Henry's law constant for methyl tert-butyl ether (MTBE) at groundwater temperatures.

The dimensionless Henry's law constant was determined for methyl tert-butyl ether (MTBE) at six temperatures (3, 5, 10, 15, 20 and 25 degrees C) by using a thermostatted flask (430 ml) containing an aqueous MTBE solution. The ratio between the gas phase and the water phase in the flask was approximately 1.7:1. The aim of this study was to acquire data needed to model the behaviour of MTBE at groundwater conditions. The dimensionless Henry's law constant at 10 degrees C is approximately 0.01 but is 0.03 at 25 degrees C. This is important for modelling MTBE because the variation of vaporization cannot be disregarded at groundwater temperatures. In a second experiment the water solubility of MTBE was determined to be 62.1 g/l at 5 degrees C and 35.5 g/l at 20 degrees C). The high solubility at low temperatures could cause MTBE plumes from spills (fuel accidents etc.) to spread rapidly.

Fresh Water↗
PubMed2004

Impact of HLA matching on outcome of hematopoietic stem cell transplantation in children with inherited diseases: a single-center comparative analysis of genoidentical, haploidentical or unrelated donors.

SUMMARY: Hematological inherited diseases can be cured by hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical sibling donor (MSD), but the outcome of unrelated donors (URD) or haploidentical donors (HMD) has been a cause of concern. In all, 94 children affected with inherited diseases underwent HSCT at a single center using MSD (group A, n=31), URD (group B, n=23) or HMD (group C, n=40). There was no difference in the rate of engraftment or in the incidence of grades III-IV acute graft-versus-host disease (GVHD) between the groups. Survival rate was 80.6% in group A, 62.5% in group B and 47.5% in group C (P=0.023). In group B, survival rate was 73.7% in the subgroup with zero or one class I mismatch, and 25% in the subgroup with two or more class I mismatches (P=0.04). In group C, survival rate was 83.3% in the 9/10-identical subgroup, 64.3% in the seven or 8/10 subgroup, and 25% in the five or 6/10 subgroup (P=0.0007). Thus, engraftment, incidence of GVHD and survival are similar in recipients of grafts from MSD, URD with 0-1 class I-mismatch, or HMD with at least 7/10 HLA matches. The low success of HSCT using more disparate donors suggests reserving them for patients with very poor prognosis.

Adolescent↗
PubMed2004

Does haploidentical transplantation in children with primary immunodeficiencies have the potential to exploit donor NK cell alloreactivity?

Donor potential to exert NK cell alloreactivity has been shown to confer survival advantage in haploidentical hematopoietic cell transplantation for hematological malignancies. We investigated killer immunoglobulin receptor (KIR) ligand incompatibility in 40 children receiving haploidentical transplantation for primary immunodeficiencies. The conditioning regimen consisted of busulfan and cyclophosphamide. T-cell depletion of the graft used complement-dependent lysis or CD34+ selection. Two patients died in the first month. The remaining 38 patients were divided into those with (n=13) and those without (n=25) donor potential to exert NK cell alloreactivity. Engraftment was similar in the two groups (61.5 and 64%, respectively). The incidence of grade II-IV acute graft-versus-host disease (GVHD) tended to be lower in the group with donor potential to exert NK cell alloreactivity, but the difference was not significant. In conclusion, in this series of patients with primary immunodeficiencies, donor potential to exert NK cell alloreactivity was not associated with significant advantages in engraftment and prevention of acute GVHD.

Child, Preschool↗
PubMed2004

The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML).

The International Prognostic Scoring System (IPSS) for myelodysplastic syndrome (MDS) is based upon weighted data on bone marrow (BM) blast percentage, cytopenia, and cytogenetics, separating patients into four prognostic groups. We analyzed the value of the IPSS in 142 children with de novo MDS and 166 children with juvenile myelomonocytic leukemia (JMML) enrolled in retro- and prospective studies of the European Working Group on childhood MDS (EWOG-MDS). Survivals in MDS and JMML were analyzed separately. Among the criteria considered by the IPSS score, only BM blasts <5% and platelets >100 x 10(9)/l were significantly associated with a superior survival in MDS. In JMML, better survival was associated with platelets >40 x 10(9)/l, but not with any other IPSS factors including cytogenetics. In conclusion, the IPSS is of limited value in both pediatric MDS and JMML. The results reflect the differences between myelodysplastic and myeloproliferative diseases in children and adults.

Child↗
PubMed2004

Severe pulmonary hypertension: a frequent complication of stem cell transplantation for malignant infantile osteopetrosis.

This report describes eight infants who developed acute severe pulmonary arterial hypertension (PAH) at days -2 to +89 after allogeneic stem cell transplantation (SCT) for malignant infantile osteopetrosis (MIOP). They were taken from a total of 28 children (frequency 29%) transplanted for this disease at three institutions between 1996 and 2002. Typical presentations were acute dyspnoea, hypoxia and brady/tachycardia usually in the absence of fever, crepitations or other evidence of infection. Six patients (75%) required assisted ventilation and five (62%) died. There was clinical or pathological evidence of veno-occlusive disease (VOD) in three children, but absence of VOD in the remaining five suggests that a separate disease process may be responsible for the PAH. Responses to nitric oxide (NO), defibrotide (DF), nicardipine and steroids in varying combinations were disappointing. Three children showed sustained improvement after administration of epoprostenol (EP, prostacyclin) in conjunction with NO and/or DF and remain well and free of PAH 25, 31 and 32 months post-transplant. PAH must therefore be excluded in any child who becomes acutely breathless after SCT for osteopetrosis.

Antihypertensive Agents↗
PubMed2004

[Vasoactive intestinal polypeptide in the respiratory tract: physiology and pathophysiology].

Peptidergic neuromediators have gained importance in the field of respiratory physiology and pathophysiology due to the characterisation of numerous pulmonary effects in the past years. With regard to the multitude of mediators, the neuropeptide vasoactive intestinale polypeptide (VIP) plays a special role as it exerts potent anti-inflammatory and immunomodulatory effects. Neurophysiologically the peptide has been attributed to the family of the inhibitory non-adrenergic non-cholinergic (i-NANC) neuromediators of the pulmonary innervation. VIP-containing nerve fibres are localized in the airway and vascular smooth muscle layers of trachea and bronchi in the human respiratory tract. Apart from strong vasodilatory effects, the peptide also shows a high bronchodilatory potency. In a large number of respiratory diseases VIP may play a pathophysiological role. In this respect, increased levels of VIP have been demonstrated for inflammatory diseases of the upper and lower airways and the peptide may also play a role in pulmonary hypertension. Due to its fast enzymatic cleavage, VIP-based therapies have not been used in routine therapy so far. Also, the use of synthetic VIP-agonists did not lead to an improved outcome in patients with bronchial asthma if compared to classical drugs. However, recent data from animal experiments indicate potent immunomodulatory effects which suggest a future use of this mediator and its agonists in the therapy of immune diseases.

Anti-Inflammatory Agents↗
PubMed2004

Phenotypic alteration of neuropeptide-containing nerve fibres in seasonal intermittent allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is the most common allergic disease affecting the respiratory tract. Next to inflammatory changes, the airway innervation plays an important modulatory role in the pathogenesis of the disease. OBJECTIVE: To examine the participation of different neuropeptides in the human nasal mucosa of intermittent (seasonal) AR tissues in the allergic season. METHODS: Immunohistochemistry for substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide tyrosine (NPY) was related to the characterization of inflammatory cells in tissues of patients with seasonal AR (n=18). RESULTS: While there was a significant increase in the number of eosinophils present if compared with a control group, no changes occurred in mast cell numbers. Immunostaining was abundantly found in different nerve fibre populations of both groups. SP expression was significantly increased in mucosal nerve fibres of patients with intermittent (seasonal) AR. Also, significantly increased numbers of VIP- and NPY-immunoreactive nerve fibres were found in biopsies of rhinitis patients in comparison with sections of normal human nasal mucosa. In contrast, CGRP expression did not change significantly. CONCLUSION: The increase of neuropeptide expression in mucosal nerve fibres indicates a major role of the autonomous mucosal innervation in the pathophysiology of intermittent (seasonal) AR.

Biopsy↗
PubMed2004

Nerve growth factor-induced substance P in capsaicin-insensitive vagal neurons innervating the lower mouse airway.

BACKGROUND: Nerve growth factor (NGF) is elevated in allergic diseases such as bronchial asthma and can lead to an induction of substance P (SP) and related neuropeptides in guinea-pigs large-diameter, neurofilament-positive airway neurons. OBJECTIVE: In the present study, the effect of NGF on tyrosine kinase receptor trkA and the capsaicin receptor TRPV1 expression in airway-specific vagal sensory neurons located in the jugular-nodose ganglia complex (JNC) of mice was investigated. METHODS: Using retrograde neuronal tracing in combination with double-labelling immunohistochemistry, SP, trkA- and TRPV1-receptor expression was examined in airway-specific sensory neurons of BALB/c mice before and after NGF treatment. RESULTS: NGF injected into the lower airway was able to induce SP (13.0+/-2.03% vs. 5.9+/-0.33%) and trkA expression (78+/-2.66% vs. 60+/-2.11%) in larger diameter (>25 microm), capsaicin-insensitive and trkA-positive vagal sensory neurons that were retrograde-labelled with Fast Blue dye from the main stem bronchi. CONCLUSION: Based on the extent of SP and trkA co-expression in airway-specific neurons by NGF treatment, the present study suggests that, following a peripheral activation of trkA receptor on SP afferent by NGF which is elevated in allergic inflammation, there may be trkA-mediated SP induction to mediate neurogenic airway inflammation.

Animals↗
PubMed2004

Expression of tyrosine hydroxylase and neuropeptide tyrosine in mouse sympathetic airway-specific neurons under normal situation and allergic airway inflammation.

BACKGROUND: The traditional neurotransmitter catecholamine and the neuropeptide tyrosine in sympathetic airway nerves have been proposed to be involved in the pathogenesis of airway diseases. OBJECTIVE: The aim of the present study was to investigate the effect of allergic airway inflammation on the expression of catecholamine enzyme tyrosine hydroxylase (TH), neuropeptide tyrosine (NPY) and tachykinins in mouse sympathetic airway ganglia. METHODS: Using neuronal tracing in combination with immunohistochemistry, the present study was designed to characterize TH, NPY and tachykinin profiles of superior cervical (SCG) and stellate ganglia after allergen challenge. RESULTS: The vast majority of fast blue-labelled SCG neurons (allergen: 97.5+/-1.22% (mean+/-SEM) vs. controls: 94.5+/-1.48%, P=0.18) and stellate neurons (allergen: 95.3+/-1.01% vs. controls: 93.6+/-1.33%, P=0.34) were immunoreactive for TH. Of the TH immunoreactive and fast blue-labelled SCG neurons, 52.0+/-1.01% allergen vs. 51.2+/-3.58% controls (P=0.83) and stellate neurons, 57.3%+/-0.97 allergen vs. 56.4+/-1.65% controls (P=0.64) were positive for TH only but not NPY, whereas 45.3+/-1.05% allergen vs. 43.3+/-1.18% controls (P=0.47) of fast blue-labelled SCG neurons and 37.9+/-0.86% allergen vs. 37.1+/-1.24% controls (P=0.62) of fast blue-labelled stellate neurons were immunoreactive for both TH and NPY immunoreactivities. There was a trend of an increase, but not significant one, in the percentage of TH-/NPY-immunoreactive and fast blue-labelled neurons in allergen-treated animals in comparison with the controls. Tachykinins, however, were not expressed by sympathetic neurons and were also not induced in sympathetic neurons after allergen challenge. CONCLUSION: The present study indicates that allergic airway inflammation does not alter the expression of noradrenalin and NPY in sympathetic ganglia and also shows that sympathetic neurons do not respond to allergic airway inflammation with tachykinins induction. However, a participation of catecholamine and NPY in the pathogenesis of allergic airway inflammation cannot be excluded in the present study as a higher neurotransmitter output per neuron following allergen challenge could be possible.

Allergens↗
PubMed2004

Neurogenic mechanisms in bronchial inflammatory diseases.

Neurogenic inflammation encompasses the release of neuropeptides from airway nerves leading to inflammatory effects. This neurogenic inflammatory response of the airways can be initiated by exogenous irritants such as cigarette smoke or gases and is characterized by a bi-directional linkage between airway nerves and airway inflammation. The event of neurogenic inflammation may participate in the development and progression of chronic inflammatory airway diseases such as allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as substance P and neurokinin A, or calcitonin gene-related peptide. Also, other biologically active peptides such as neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids may modulate the inflammatory response and recently, novel tachykinins such as virokinin and hemokinins were identified. Whereas the different aspects of neurogenic inflammation have been studied in detail in laboratory animal models, only little is known about the role of airway neurogenic inflammation in human diseases. However, different functional properties of airway nerves may be used as targets for future therapeutic strategies and recent clinical data indicates that novel dual receptor antagonists may be relevant new drugs for bronchial asthma or COPD.

Animals↗
PubMed2004

Simple DNA extraction method for dried blood spots and comparison of two PCR assays for diagnosis of vertical human immunodeficiency virus type 1 transmission in Rwanda.

Dried blood spots (DBS) on filter paper facilitate the collection, transport, and storage of blood samples for laboratory use. A rapid and simple DNA extraction procedure from DBS was developed and evaluated for the diagnosis of human immunodeficiency virus type 1 (HIV-1) infection in children by an in-house nested-PCR assay on three genome regions and by the Amplicor HIV-1 DNA prototype assay version 1.5 (Roche Molecular Systems). A total of 150 samples from children born to HIV-1-infected mothers were collected in Kigali, Rwanda, in parallel as DBS and as peripheral blood mononuclear cell (PBMC) pellets. The results obtained on DBS by the two PCR assays were compared to the results of nested PCR on PBMCs. Of 150 PBMC samples, 10 were positive, 117 were negative, and 23 were indeterminate for HIV-1 infection. In DNA extracted from filter papers and amplified by using the in-house nested PCR, 9 of these 10 positive samples (90%) were found to be positive, and 1 was found to be indeterminate (only the pol region could be amplified). All of the negative samples and all of the 23 indeterminate samples tested negative for HIV-1 infection. When we used the Amplicor DNA test on DBS, all of the 10 PBMC-positive samples were found to be positive and all of the 23 indeterminate samples were found to be negative. Of the PBMC-negative samples, 115 were found to be negative and 2 were found to be indeterminate. We conclude that this simple rapid DNA extraction method on DBS in combination with both detection methods gave a reliable molecular diagnosis of HIV-1 infection in children born to HIV-infected mothers.

Acquired Immunodeficiency Syndrome↗
PubMed2004

beta-Catenin expression in thyroid follicular lesions: potential role in nuclear envelope changes in papillary carcinomas.

The morphologic distinction of benign and malignant thyroid follicular lesions can sometimes be challenging, therefore an immunohistochemical marker to aid in this distinction would be useful. beta-Catenin is one such potential marker. It is part of a membrane-bound cell growth-signaling complex that plays a role in cell adhesion, as well as in promotion of growth through activation of the Wnt signaling pathway. Oncogenic signaling occurs when beta-catenin is released, accumulates in the cytoplasm, translocates into the nucleus, and promotes transcription of genes including bcl-1 (cyclin D1) and c-myc that induce cell proliferation. Paraffin blocks from 133 thyroidectomy specimens were stained with monoclonal antibodies reactive with beta-catenin and cyclin D1. These included 53 cases of papillary thyroid carcinoma (PTC), 46 cases of follicular variant of papillary carcinoma (FVPC), 10 cases of follicular carcinoma (FC), and 24 cases of follicular adenoma (FA). Tissue from six normal thyroid specimens served as a control. The malignant lesions (PTC, FC, and FVPC) expressed strong cytoplasmic/nuclear staining and minimal residual membranous staining in 87%, 80%, and 71% of cases, respectively. In contrast, all normal thyroid tissue and 79% of FAs showed strong membranous reactivity with very minimal cytoplasmic staining. Interestingly, in 83% of PTC cases and 20% FVPCs, the intranuclear inclusions were distinctly beta-catenin positive. Cyclin D1 over expression correlated with cytoplasmic relocalization of beta-catenin in almost all cases, and no evidence of cyclin D1 gene amplification was observed. beta-Catenin can be of a diagnostic utility for thyroid lesions, because it highlights intranuclear inclusions in PTC, and shifts from a membranous localization to a cytoplasmic localization in malignant lesions. We speculate that the localization of beta-catenin in intranuclear inclusions may reflect a cytoskeletal remodeling activity of beta-catenin that is functionally significant for the PTC pathway.

Adenocarcinoma, Follicular↗
PubMed2003

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.

We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

Adaptor Proteins, Signal Transducing↗
PubMed2003

[The heart transplant in Lausanne from 1987 to 2003].

Since the availability of ciclosporine, the survival after heart transplantation has dramatically improved. We present our results since the beginning of our experience in 1987. We treated in the Lausanne University hospital, 150 patients for end-stage cardiac disease. Hundred and fifty-two transplantations were performed. The survival rate is comparable to the literature with 81% at one year, 70% at five year and 63 at ten year included the hospital mortality. We review the incidence of complications during the follow-up and report the modification in the management of these patients especially concerning the immunosuppression.

Adult↗
PubMed2003

Hematopoietic stem cell transplantation in patients with severe Langerhans cell histiocytosis and hematological dysfunction: experience of the French Langerhans Cell Study Group.

The aim of this study was to assess the results of hematopoietic stem cell transplantation (HSCT) in refractory Langerhans cell histiocytosis (LCH). Among 85 patients with LCH and hematological dysfunction diagnosed in France between 1987 and 2000, eight received HSCT in six institutions. Median age at diagnosis was 0.54 years. The median LCH activity score at diagnosis was 10 (range 3-20). All patients responded poorly to initial chemotherapy. At the time of HSCT, the median activity score was 16.5 (range 7-18). HSCT was autologous in three cases and allogeneic in five cases. The conditioning regimen consisted of TBI in two cases and chemotherapy alone in six cases. Conditioning had to be attenuated in two patients. All patients had persistent active disease after autologous HSCT, which was fatal in two cases and controlled by chemotherapy in one case. After allogeneic HSCT, two patients died from toxicity and three had complete responses; two patients had had no recurrences after 21 months and 7 years of follow-up, while the other patient relapsed and died from sepsis related to splenectomy. HSCT for refractory LCH can thus be highly toxic but can also achieve sustained disease control.

Chimera↗
PubMed2003

Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report.

A retrospective analysis was made of 122 children who had received an allogeneic haematopoietic stem cell transplantation (HSCT) for autosomal recessive osteopetrosis between 1980 and 2001. The actuarial probabilities of 5 years disease free survival were 73% for recipients of a genotype HLA-identical HSCT (n=40), 43% for recipients of a phenotype HLA-identical or one HLA-antigen mismatch graft from a related donor (n=21), 40% for recipients of a graft from a matched unrelated donor (n=20) and 24% for patients who received a graft from an HLA-haplotype-mismatch related donor (n=41). In the latter group, a trend towards improvement was achieved at the end of the study period (17% before 1994, 45% after 1994, P=0.11). Causes of death after HSCT were graft failure and early transplant-related complications. Severe visual impairment was present in 42% of the children before HSCT. Conservation of vision was better in children transplanted before the age of 3 months. Final height was related to height at the time of HSCT and better preserved in children transplanted early. Most children attended regular school or education for the visually handicapped. At present, HSCT is the only curative treatment for autosomal recessive osteopetrosis and should be offered as early as possible.

Body Height↗
PubMed2003

Autoimmune lymphoproliferative syndromes: genetic defects of apoptosis pathways.

Human and mouse natural mutants presenting with lymphoproliferative syndrome and autoimmunity (ALPS) have enlightened the role of the Fas and FasL in lymphocyte cell death and peripheral tolerance. Further study of the genetic basis of the human pathology led to the identification of apoptosis signaling defect, and pointed out to the crucial role of caspase-10 in the process of apoptosis induction. In contrast, the absence of lymproliferation in engineered mutants of 'death pathways' suggests that additional events are necessary to recapitulate the overt phenotype of ALPS patients or MRL/lpr mice. Moreover, these models highlight the roles of Fas and associated molecules, such as FADD and caspase-8, in lymphocyte development or activation. This review will discuss the main findings provided by the study of mouse models and human conditions.

Adaptor Proteins, Signal Transducing↗