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Biomedical subjects

A Fischer

Publications and source records attributed to A Fischer.

At least 379 records · Page 21Linked to original sources
PubMed1996

Correction of congenital erythropoietic porphyria by bone marrow transplantation.

Congenital erythropoietic porphyria (Gunther disease) is a rare metabolic disorder caused by uroporphyrinogen III synthetase deficiency. We report the case of a 2-year-old girl with a severe form of this disease who received HLA-identical bone marrow transplantation from her heterozygous sister. Two transplantations were necessary to obtain full hematopoietic chimerism. Correction of the enzyme deficiency was confirmed by measuring erythrocyte uroporphyrinogen III synthetase activity. The patient's clinical condition improved dramatically, and she is well 1 year after the second transplantation, with no further treatment. Although long-term efficacy remains to be confirmed, we conclude that allogeneic bone marrow transplantation can cure patients with congenital erythropoietic porphyria.

Bone Marrow Transplantation↗
PubMed1996

Isolated X-linked thrombocytopenia in two unrelated families is associated with point mutations in the Wiskott-Aldrich syndrome protein gene.

The Wiskott-Aldrich syndrome (WAS) is characterized by defective platelet and lymphocyte function associated with eczema and increased susceptibility to malignancies. It is caused by mutations of the WAS protein-encoding gene (WASP). X-lined thrombocytopenia, defined by low platelet counts and volume, may be an allelic variant of WAS. In patients with XLT from two unrelated families, WASP gene defects were identified by single-strand conformational polymorphism and by sequencing. Point mutations in exon 2 of the WASP gene were found in the patients from both families in which XLT segregated. Several obligate heterozygote female members of these families display a random pattern of X inactivation in their peripheral blood leukocytes. This study shows that XLT may be caused by mutations of the WASP, thus representing an allelic variant of WAS.

Adult↗
PubMed1996

Bone marrow transplantation in 26 patients with Wiskott-Aldrich syndrome from a single center.

We retrospectively analyzed the outcome of bone marrow transplantation (BMT) performed in 26 patients with Wiskott-Aldrich syndrome (WAS) in one center. Twenty-eight transplantation procedures were performed. Ten unselected patients received unmanipulated marrow from a donor with genetically identical human leukocyte antigen (HLA). Eight patients were cured and survive 1.5 to 16.5 years after BMT. One patient successfully received a T-cell-depleted marrow from a matched unrelated donor. Sixteen patients were selected to receive a related HLA partially incompatible BMT because of the occurrence of life-threatening complications from the WAS (i.e., refractory thrombocytopenia, autoimmunity including vasculitis and sepsis). All but one received T-cell-depleted marrow after a conditioning regimen of busulfan and cyclophosphamide. One patient had two BMTs. Engraftment occurred in 12 of 17 attempts. The addition of monoclonal antibodies to lymphocyte function-associated antigen-1 and CD2 molecules appeared to improve engraftment. Six patients were long-term survivors, whereas others died of viral infections (n = 7), among which Epstein-Barr virus-induced B-lymphocyte proliferative disorder was predominant. Delay in development of full T- and B-cell functions accounted for severe infectious complications. These results confirm the excellent outcome of HLA genetically identical BMT in WAS, whereas BMT from HLA partially incompatible donors should be strictly restricted to patients with severe complications of WAS.

Adolescent↗
PubMed1996

Pathogenicity of IgA and/or IgM antibodies to heparin-PF4 complexes in patients with heparin-induced thrombocytopenia.

Antibodies to heparin-PF4 (H-PF4) complexes have been tested and isotyped in 38 patients who developed severe heparin-induced thrombocytopenia (type II HIT). All patients had a platelet count <120x10(9)/1 or a reduction of > 30% of the initial value, occurring at least 5d after the onset of heparin. Thrombocytopenia, which rapidly reversed following the withdrawal of heparin, was associated with thrombosis in nine patients. Although IgG isotypes were found in most cases (n=26), the presence of only IgM and/or IgA was observed in 12 patients, including three cases showing a thrombotic complication. Our results indicate that type II HIT may be induced by IgA and /or IgM anti-H-PF4 antibodies even in the absence of IgG isotypes. This finding demonstrates that platelet Fc receptors (FcgammaRII) are not necessarily involved in the pathogenicity of heparin-dependent antibodies and emphasizes the major role of platelet PF4 receptors. The increased expression of the latter following a slight activation by thrombin, and the subsequent binding of IgM and IgA antibodies to H-PF4 on the platelet surface, may directly trigger platelet activation aggregation and thrombosis. Alternatively, thrombocytopenia could be indirectly induced through the mediation of neutrophils, monocytes and lymphocytes which expose receptors for IgA (FcalphaR) or IgM FcmuR). IgM-platelet complexes may also bind and activate complement, leading to platelet activation or destruction. Moreover, the reactivity of the antibodies with glycosaminoglycans-PF4 complexes present on the endothelial surface could also induce endothelial lesions and promote procoagulant activity and predisposition to thrombosis.

Adult↗
PubMed1996

A phase II trial of partially incompatible bone marrow transplantation for high-risk acute lymphoblastic leukaemia in children: prevention of graft rejection with anti-LFA-1 and anti-CD2 antibodies. Société Française de Greffe de Moelle Osseuse.

Bone marrow transplantation (BMT) from matched sibling donors has been useful for the treatment of acute lymphoblastic leukaemia in children with a poor prognosis but is not available to more than two-thirds of patients who do not have a matched allogeneic donor. This study was undertaken to assess one strategy of marrow graft rejection prevention when alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives were used. Results have been compared with two matched groups of children with the same risks factors and disease status who underwent HLA-genoidentical or autologous BMT. The conditioning regimen was the same for the three groups of patients; in the study group anti-LFA-1 and anti-CD2 monoclonal antibodies combined with T-cell depletion of the marrow was added to prevent graft rejection and graft-versus-host disease. Nineteen patients were included and followed for a median of 25 months (14 months to 3 years). Bone marrow engraftment occurred in 83% of the evaluable patients. Post-transplantation infectious diseases were the most frequent causes of death in the study group, occurring in 31% of patients. No fatal infections occurred in the two control groups. Post-transplantation relapse of leukaemia occurred in 26% of study group's patients, in 58% of autologous BMT control group's patients and 5% of HLA-genoidentical allogeneic group's patients. The event-free survival was 83% in the HLA-genoidentical control group, and 30% and 24% in the study group and in the autologous control group, respectively. In conclusion, a high rate of engraftment was achieved by the use of anti-LFA-1 and anti CD2 antibodies. Occurrence of a long-lasting immunodeficiency, however, led to a high incidence of lethal infections and relapses. Combined approaches are therefore to be investigated accelerating immune reconstitution after transplantations of T-depleted HLA partially incompatible marrow.

Adolescent↗
PubMed1996

[Addition of ethanol to the distension medium in surgical hysteroscopy as screening to prevent "fluid overload". A prospective randomized comparative study of ablative versus non-ablative surgical hysteroscopy and different ethanol concentration].

For answering the question at which hysteroscopical procedures an intraoperative screening method is necessary to avoid a fluid overload and whether a beginning fluid absorption can be diagnosed early by adding ethanol to the distension medium, a prospectively randomised comparative study of ablative versus non-ablative operative hysteroscopy with differing ethanol concentrations was performed (n = 120). Purisole (a mannit/sorbit solution) was used a distension medium. The measuring parameters (breath alcohol, amount of absorbed fluid, haematocrit and haemoglobin values, central venous pressure, heart frequency) were intraoperatively determined at 5-minute intervals. The results of the study show that with those hysteroscopical procedures during which the endometrium is not or only minimally injured (e.g. syneciolysis, hysteroscopic proximal tubal catheterisation). Intraoperative screening is not necessary due to the low absorbing amounts. With hysteroscopical procedures such as resection of myoma, endometrium ablation and septum resection, however, an addition of ethanol of 2% to the distension medium has proved useful, because with this method absorption amounts of 400 ml and more can be detected by positive values of breath alcohol. As the result of a further absorption of fluid, delayed in time compared to the first positive value of breath alcohol, there is an increase in central venous pressure and hyponatraemia. Intraoperative ethanol monitoring is a non-invasive procedure which can be performed during ablative-operative hysteroscopies and has no negative influence on the course of the intervention and the general condition of the patients.

Adult↗
PubMed1996

A synthetic peptide mimicking the HLA-DR beta 2-binding site for CD4 inhibits antigen-independent CD4+ T cell adhesion to B cells and CD4+ T cell activation.

We studied the ability of a peptide mimicking the major binding site of HLA-DR beta 2 for CD4 (i.e. amino acids 134-148) to inhibit the adhesion of CD4+ T cells to B cells and ICAM-1-DR-expressing fibroblasts, as well as the proliferation of TCR-CD3-triggered CD4+ T cells. Peptide DR134-148 blocked CD4+ T cell (but not CD8+ T cell) binding to B cells and to DR+ ICAM-1+ fibroblasts in a concentration-dependent manner. A peptide composed of randomly associated identical amino acid residues had no effect. This inhibitory activity was not additive with the effect of an anti-CD4 antibody, peptide DR35-46 (mimicking another potential binding site of HLA-DR beta 1 to CD4) or an anti-LFA-1 antibody. Adhesion of a T cell line (HUT78) expressing a mutated form of CD4 unable to bind p56lck cytosine kinase was not inhibited by peptide DR134-148. In addition, herbimycin A, a tyrosine kinase inhibitor, abrogated the inhibitory activity of DR134-148. Since CD4-MHC class II interactions have been shown to play no detectable role in mediating antigen-independent adhesion in this assay, peptide interactions with CD4 may trigger an off signal down-regulating LFA-1-mediated adhesion. Indeed, adhesion of CD4+ T cells to ICAM-1- fibroblasts was not inhibited by peptide DR134-148, while the same peptide inhibited antigen (protein-pure derivative)- and anti-CD3 antibody-induced CD4 T cell proliferation. These findings suggest that the major sequence involved in the MHC class II interaction with CD4 is sufficient to induce a downstream negative regulatory signal that is mediated by p56lck, independently of antigen-specific TCR triggering.

Amino Acid Sequence↗
PubMed1996

Impact of the implantable cardioverter-defibrillator on rehospitalizations.

UNLABELLED: Patients who survive out-of-hospital ventricular tachycardia or ventricular fibrillation are at risk of sudden cardiac death and often return to hospital after initial discharge. The frequency and duration of readmittance to hospital are not well known. Thus, the purpose of this study was to evaluate the impact of the implantable cardioverter defibrillator on frequency and duration of hospitalizations. METHODS: Between 1989 and 1993, 38 consecutive patients who had drug-refractory ventricular tachyarrhythmias were selected for the study. A total of 38 patients were implanted with the implantable cardioverter-defibrillator in accordance with the guidelines of the European Society of Cardiology. This analysis includes 35 of the 38 patients (92%). All hospitalizations which occurred one year before and one year after were studied. Clinical information for all patients was obtained by consulting medical records and by interviewing personal general practitioners. RESULTS: The annual number of hospitalizations before and after implantation of the implantable cardioverter-defibrillator was, respectively, 3.28 +/- 2.38 hospitalizations/ patient/year and 0.88 +/- 1.23 hospitalizations/patient/year (P < 0.05). Before implantation of the implantable cardioverter-defibrillator, patients were hospitalized a mean of 32.94 +/- 24.18 days/patient/year and after, 9.31 +/- 32.14 days/patient/year (P < 0.05). The number of hospitalizations for cardiac reasons decreased by 90%. Before implantation, the most frequent cause was ventricular tachyarrhythmia (47 hospitalizations for ventricular tachycardia and eight for ventricular fibrillation), while after implantation, it was as a result of the shock from the implantable cardioverter-defibrillator (11 hospitalizations). The number of hospitalizations for non-cardiac reasons were similar in the two time periods. Of the 35 patients, 26 (74%) had at least one appropriate successful ventricular tachycardia interrupted by the implantable cardioverter-defibrillator, while 17 patients (49%) had their ventricular fibrillation terminated. There is a significant difference in the rate of hospitalizations to intensive care units (ICU) between the two periods. Before implantation, 30% of hospital days were spent in the ICU, with 3% after. CONCLUSIONS: This study documents that the implantable cardioverter-defibrillator not only reduces the frequency and duration of hospital stays, but reduces admissions to the more expensive units in hospital. Taking into account the reduction in hospitalizations, the payback period for the implantation of an implantable cardioverter-defibrillator is 19 months.

Adolescent↗
PubMed1996

Basic innervation pattern and distribution of classic autonomic neurotransmitters in human nasal mucosal vasculature.

The neural control of human nasal vasculature is still not completely understood. This study was performed to demonstrate the innervation pattern of the different vessel types and to distinguish between nor-adrenergic and cholinergic structures. General innervation was demonstrated using antibodies to neuron-specific enolase and S-100 protein. Autonomic structures were shown by using antibodies to tyrosine hydroxylase and choline acetyltransferase (ChAT). In addition, choline acetyltransferase (AChe) histochemistry was performed. Nasal vasculature is controlled by a dense innervation that increases with the thickness of the tunica media. While all larger vessels show a mixed autonomic innervation, sympathetic structures seem to predominate in veins. These findings demonstrate that classic neurotransmitters play a major role in the regulation of nasal vasculature. The stronger innervation of arteries and cushion veins underlines their central position in the control of nasal air flow.

Adrenergic Fibers↗
PubMed1996

Mite control with low temperature washing. I. Elimination of living mites on carpet pieces.

BACKGROUND: Washing of delicate textiles at low temperature combined with mite control is one of the important aims for domestic mite prevention. OBJECTIVES: Estimation or assessment of mite numbers without and after the application of detergents or detergents with mite control additive. Trials at low temperature, detergents and washing as usual at household conditions (programme of a household washing machine). METHODS: The domestic mite Dermatophagoides farinae can be cultured on carpet samples under favourable conditions, and the breeding success monitored in terms of population and distribution using the free mite mobility test. The mite containing carpets were cut into pieces in order to investigate the effects of washing at low temperature with different commercial detergents with and without an additive for mite control. The heat escape method was used to assess the number of mites remaining on the carpet pieces. RESULTS: The estimation of the mite populations on different carpet pieces before and after washing showed that between 40 and 60% of the mites were able to resist washing, rinsing, spinning and drying. The allergen containing dust, however, was flushed out. In contrast, complete mite control was achieved by the application of the same detergents together with an additive. CONCLUSION: Mite control by low temperature washing is possible with a mite control additive provided that a concentration of benzyl benzoate of about 0.03% is achieved in the washing suds.

Animals↗
PubMed1996

Nitric oxide synthase in neurons and nerve fibers of lower airways and in vagal sensory ganglia of man. Correlation with neuropeptides.

The mediator accounting for the major relaxant responses to electrical field stimulation of human airways was previously identified as nitric oxide (NO). In the present study, we examined the distribution of the neuronal isoform of the NO-generating enzyme, nitric oxide synthase (bNOS, type I NOS) in nerve fibers of the human airways (trachea, large and small bronchi, bronchioli) as well as in human intrinsic and sensory ganglia of airway innervation by means of quantitative histochemistry (NADPH-diaphorase technique) and immunohistochemistry. Correlation with substance P (SP) and vasoactive intestinal peptide (VIP) was performed by double-labeling immunohistochemistry. NOS-containing nerve fibers were found to be present in the airway smooth muscle, around submucosal glands, around blood vessels and, very rarely, in the lamina propria. The innervation density of airway smooth muscle by NOS-containing nerve fibers decreased significantly from trachea to large-diameter bronchi to small-diameter bronchi, whereas NOS-containing nerve fibers were completely absent from bronchioli. Colocalization of NOS with VIP but not with SP was frequent in these nerve fibers. In airway intrinsic ganglia, the number of NOS-containing neuronal cell bodies increased from 57% in the trachea up to 83% in small bronchi. Around these perikarya, many nerve fibers displaying VIP-immunoreactive (VIP-IR) or SP-IR were found. In the superior vagal sensory (i.e., jugular) ganglion most of the neuronal cell bodies contained either NOS-IR or SP-IR; a colocalization of both was not as frequent. These data contribute to the understanding of the morphologic basis underlying the functional differences of the neural relaxant responses mediated by NO at different levels of the airway tree.

Bronchi↗
PubMed1996

Radiommunological measurement of leptin in plasma of obese and diabetic human subjects.

Studies in mice have identified the ob gene product, leptin, as a signaling factor regulating body weight homeostasis and energy balance. Defective production of the encoded protein may be one of the causes for the development of obesity. Using a high affinity antibody, that in immunohistochemical studies specifically stained human adipocytes, a radioimmunoassay was established and leptin immunoreactivity was quantified in plasma of lean and obese human subjects. Chromatographic analysis suggested that the immunoreactive material in plasma is identical to that found in extracts from human fat and represent a protein with a molecular size of approximately 16 kD. Fasting levels were measured in plasma of 75 lean and obese human subjects (body mass index (BMI) 17.7 - 87.3). The mean concentration of leptin in plasma of lean subjects (BMI < or = 28) was 69.3 +/- 36.9 fmol/ml plasma (mean +/- SD, n=27). The highest concentration measured in obese was 533.3 fmol/ml plasma. The levels showed a strong positive correlation with BMI (r=0.77, p<0.001). A subgroup of diabetic patients did not significantly differ in their leptin plasma levels from non-diabetic subjects with similar BMI.

Adult↗
PubMed1996

Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, often fatal, disease of early infancy. The diagnosis of HLH is frequently delayed or made at autopsy because no genetic or biologic marker has been identified. To improve the classification and treatment of HLH, the Histiocyte Society has established an 'International Registry for HLH'. Data collected included family history, clinical and laboratory features at the onset of illness, and treatment outcome. Stringent diagnostic criteria (ie fever, splenomegaly, cytopenia, hypertriglyceridemia, and/or hypofibrinogenemia, and hemophagocytosis without evidence of malignancy) were used for patient selection. One hundred and twenty-two patients (61 males, 61 females) were enrolled from 17 centers in 11 countries. The rate of parental consanguinity was 24%. A positive family history was reported in 49% of cases including two pairs of affected male twins. The median age at disease onset was 2.9 months, with no difference between familial and sporadic cases. Age at onset was similar in affected sibs from 10 of 14 families, but in four up to 3-year differences were observed. Hemophagocytosis was present at diagnosis in 75%. An associated infection (usually by common viral pathogens) was reported in 50 of the 122 (41%) cases, of which 25 had familial disease. Natural killer activity was impaired in 36 of 37 patients studied. Chromosome analysis was normal in all tested patients. A decreased frequency of HLA-B7 and B8 alleles and increased frequency of HLA-B21 and DQ3 were observed. The estimated 5-year survival (SE) was 21% (18.7) for all patients. It was 66% (37.8) for patients who received allogeneic bone marrow transplant and 10.1% (9.6) for patients treated with chemotherapy alone (P=0.0001). None of the previously proposed prognostic indicators (age, associated infection, cerebrospinal fluid pleocytosis, family history) correlated with treatment outcome.

Age of Onset↗
PubMed1996

Metabolism of oocyte construction and the generation of histospecificity in the cleaving egg. Lessons from nereid annelids.

The growing oocyte and the developing egg of nereid polychaetes are easily accessible to observation and experimental work, a precondition for our research. In preparation for a single semelparous act of reproduction, nereid females reutilize somatic biomass for the synchronized production of numerous oocytes. To keep oogenesis going somatic resources become recycled by the eleocytes and are supplied to the oocytes in form of vitellogenin and nucleotides (among other identified and yet unidentified substances). Both oocytes and eleocytes are free-floating coelomic cells. We postulate that availability of metabolites produced by the eleocytes might suffice to drive synchronous oocyte growth. The cortex of the fully differentiated oocyte contains numerous cortical granules which after fertilization empty by exocytosis thus causing a profound structural reorganization of the zygote cortex. Early development of nereids is extremely constant in time and spatial pattern and from the onset cleavages create diversity among the blastomeres. We have documented a correlation between the quality and amount of cytoplasm, the cell cycle duration and the histogenetic fate of such blastomeres. Experimental change of cytoplasmic proportions of early cleavage cells has serious consequences for axial development. Using a number of differentiation markers we were able to analyze the necessity of certain cleavage steps for the acquisition of the determined state.

Amino Acids↗
PubMed1996

Genetic and physical mapping of the Chediak-Higashi syndrome on chromosome 1q42-43.

The Chediak-Higashi syndrome (CHS) is a severe autosomal recessive condition, features of which are partial oculocutaneous albinism, increased susceptibility to infections, deficient natural killer cell activity, and the presence of large intracytoplasmic granulations in various cell types. Similar genetic disorders have been described in other species, including the beige mouse. On the basis of the hypothesis that the murine chromosome 13 region containing the beige locus was homologous to human chromosome 1, we have mapped the CHS locus to a 5-cM interval in chromosome segment 1q42.1-q42.2. The highest LOD score was obtained with the marker D1S235 (Zmax = 5.38; theta = 0). Haplo-type analysis enabled us to establish D1S2680 and D1S163, respectively, as the telomeric and the centromeric flanking markers. Multipoint linkage analysis confirms the localization of the CHS locus in this interval. Three YAC clones were found to cover the entire region in a conting established by YAC end-sequence characterization and sequence-tagged site mapping. The YAC contig contains all genetic markers that are nonrecombinant for the disease in the nine CHS families studied. This mapping confirms the previous hypothesis that the same gene defect causes CHS in human and beige pheno-type in mice and provides a genetic framework for the identification of candidate genes.

Animals↗