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Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 181 records · Page 10Linked to original sources
PubMed1998

Thermic effects in the "vestibule" during laser stapedotomy with pulsed laser systems.

BACKGROUND AND OBJECTIVE: Apart from the ablation properties at the stapes footplate, the degree of thermic loading in the inner ear is important in determining the suitability of pulsed lasers for stapedotomy. The aim of the study is to compare the thermic effects in the vestibule with different pulsed laser systems. STUDY DESIGN/MATERIALS AND METHODS: Temperature increases and heat exchange processes in the fluid (physiological saline) were examined in a calorically and physiologically approximated cochlea model for applying the laser parameters effective in creating footplate perforations. RESULTS: With all systems, increases in the energy density, number of pulses, and thus resultant total energy lead to higher temperatures. In the effective energy density range, the highest temperature increases achieved with the requisite number of pulses at a distance of 2 mm behind the perforation are 26 degrees C with the Ho:YAG laser. The lowest temperature maxima are 5.5 degrees C with the Er:YAG and <5 degrees C with the Er:YSGG laser. The excimer laser, investigated at only one energy density, showed maximal temperatures of 10 degrees C. CONCLUSION: The Er:YSGG and Er:YAG laser can be applied in laser stapedotomy in a relatively broad energy density range without a risk of inner ear damage by thermic loading. On the other hand, the Ho:YAG laser is not recommended for stapedotomy because of the higher energy density and pulse rate required for sufficient perforation and the resultant higher temperature increases in the perilymph. Though likewise achieving perforations with only slight temperature increases in the fluid of the cochlea model, the excimer laser does not seem appropriate for stapedotomy because of the long period of heat exposure (ca. 60 s) due to the lower ablation rate at the stapes necessitating a longer application time.

Cochlea↗
PubMed1998

Non-Hodgkin lymphoma (NHL) as a second neoplasm occurring after neuroblastoma treatment.

As far as we know, this is the first report of a non-Hodgkin lymphoma developing after successful treatment of neuroblastoma. A boy was found to have a mediastinal T-cell lymphoma at the age of 5. He had been treated for a neuroblastoma of the left adrenal region 4 years before, when by intensive chemotherapy and radiation a complete remission of the primary tumor was achieved. The second malignancy has also been controlled without evidence of recurrence 1 year after termination of treatment. We conclude that treatment of a neuroblastoma by cytostatic drugs and radiation may lead to a non-Hodgkin lymphoma as a second malignancy.

Humans↗
PubMed1998

Detection of the bcr/abl gene in bone marrow macrophages in CML and alterations during interferon therapy--a fluorescence in situ hybridization study on trephine biopsies.

A fluorescence in situ hybridization (FISH) study was performed on trephine biopsies of the bone marrow in chronic myelogenous leukaemia (CML) to evaluate the bcr/abl translocation in macrophages before and during interferon (IFN) therapy. Mature macrophages and osteoclasts were identified by the monoclonal antibody PG-M1, which recognizes a fixative-resistant epitope of the CD68 molecule. In contrast to a control group, in 145 of 479 (30 per cent) macrophages of the CML bone marrow, a positive fusion signal was found, together with corresponding translocation sites in the surrounding myeloid cells. In patients following IFN treatment for approximately 12 months and with haematological/cytogenetic remission by clinical standards, this number was reduced to 10 of 136 (9 per cent) macrophages. In addition, the few multinucleated osteoclasts of the untreated CML bone marrow displayed positive translocation spots. This finding supports the hypothesis that stromal macrophages and osteoclasts are of haematogenic stem cell origin. Moreover, clinical remission and reduction of bcr/abl-positive macrophages under IFN therapy lend support to the hypothesis that the presence of malignant stromal macrophages may contribute to the selective expansion of leukaemic precursors and the suppression of normal haematopoiesis in CML.

Antigens, CD↗
PubMed1998

Evidence for integrin receptor involvement in megakaryocyte-fibroblast interaction: a possible pathomechanism for the evolution of myelofibrosis.

Megakaryocytes are assumed to be functionally linked with the evolution of myelofibrosis, complicating chronic myeloproliferative disorders. It has already been shown that megakaryocytes will promote fibroblast growth in vitro when in spatial proximity. Here, we demonstrate that the integrin receptors alpha3beta1 and alpha5beta1 are involved in this megakaryocyte-fibroblast interaction. Upon addition of anti-alpha3 and -alpha5 antibodies to megakaryocyte-fibroblast cocultures, fibroblast growth was significantly impaired, and megakaryocyte attachment to the fibroblast feederlayer was significantly reduced. Unilateral blocking of megakaryocytes with anti-alpha3 or -alpha5 antibodies resulted in a suppression of adhesion, probably reflecting the prominent function of fibronectin receptors on the megakaryocyte surface. Moreover, the oligopeptide RGDS (Asp-Gly-Asp-Ser) caused a significant reduction of fibroblast growth as well as megakaryocyte adhesion. This feature reinforces that fibronectin receptors are involved. In addition, fibroblast proliferation was impaired by the application of fibronectin antibodies recognizing the cell-binding domain. However, no effect was observable with respect to megakaryocyte adhesion. In conclusion, our in vitro studies demonstrate the involvement of beta1-integrins, in particular the fibronectin receptor in the megakaryocyte-dependent fibroblast proliferation and therefore suggest a pivotal role of megakaryocytes in the complex pathomechanism causing myelofibrosis.

Adult↗
PubMed1998

[Langerhans cell histiocytosis in the elderly].

Disseminated Langerhans-cell-histiocytosis (LCH) is most frequent in children at the age of 1-3 years, seldomly seen in adults and extremely rare in the elderly. The clinical course may be acute, subacute or chronic, progressive or stationary. Spontaneous remissions are possible, but rare. In elderly patients often the disease is at first limited to the skin before it becomes systemic. A 73-year-old female patient with chronic stationary disease of 3.5 years duration died 4 weeks after the acute dissemination of her LCH. At the beginning, her skin and liver involvement had responded to chemotherapy with etoposide. Six months later cutaneous relapse occurred with a more disseminated pattern involving the external auditory meatus. Treatment with topical nitrogen mustard followed by thalidomide produced marked improvement. As complications an irritation after topical application of nitrogen mustard and a maculo-papular exanthem after thalidomide were noted. No further visceral involvement was documented for one year. Then the patient developed acute disseminated disease and died within four weeks. As LCH may show a highly unpredictable course with progress and spontaneous remission, the prognosis is difficult. Any therapeutical procedures should be based on the actual state of the disease as determined by careful examination of the organs most commonly involved.

Adult↗
PubMed1998

Purification and characterization of laccase II of Aspergillus nidulans.

Sexual development in Aspergillus nidulans is a morphogenetic differentiation process triggered by internal and environmental signals. As a first step in analyzing the developmental pathway at the molecular level, laccase II (EC 1.10.3.2), which is specifically expressed in early stages of fruitbodies, was isolated. The enzyme was purified to apparent homogeneity from a mutant strain (SMS1) in which the sexual cycle dominates and the number of cleistothecia is increased tenfold. Laccase II was enriched 560-fold to a specific activity of 892 U (mg protein)-1. The apparent molecular mass was determined to be 80 kDa under denaturing conditions and to be 100-120 kDa under native conditions. The internal peptide sequences gained from the protein will allow the isolation of the corresponding gene as a first step in determining the key regulators of sexual development.

Amino Acid Sequence↗
PubMed1998

Primary manifestation of Hodgkin's disease in the central nervous system.

A 62-year-old woman presented with loss of memory and a mild hemiparesis. Neuroradiology demonstrated a left frontoparietal tumour. Biopsy specimens of this lesion revealed intracerebral Hodgkin's lymphoma, a diagnosis supported by immunohistochemical reactions of the tumour cells for the CD30 antigen. Additional cell cycle studies revealed a high proliferative activity of the tumour cells in association with absence of apoptosis. There was no evidence that overexpression of bcl-2 or Epstein-Barr virus infection was involved in the pathogenesis of this neoplasm. Lymphomas in the lung were detected 3 months later. Following neurosurgical excision, radiotherapy, and chemotherapy, the patient had no evidence of Hodgkin's disease after 13 months of follow-up.

Apoptosis↗
PubMed1998

Structure and dynamics of human interphase chromosome territories in vivo.

A new approach is presented which allows the in vivo visualization of individual chromosome territories in the nuclei of living human cells. The fluorescent thymidine analog Cy3-AP3-dUTP was microinjected into the nuclei of cultured human cells, such as human diploid fibroblasts, HeLa cells and neuroblastoma cells. The fluorescent analog was incorporated during S-phase into the replicating genomic DNA. Labelled cells were further cultivated for several cell cycles in normal medium. This well-known scheme yielded sister chromatid labelling. Random segregation of labelled and unlabelled chromatids into daughter nuclei resulted in nuclei exhibiting individual in vivo detectable chromatid territories. The territories were composed of subcompartments with diameters ranging between approximately 400 and 800 nm which we refer to as subchromosomal foci. Time-resolved in vivo studies demonstrated changes of positioning and shape of territories and subchromosomal foci. The hypothesis that subchromosomal foci persist as functionally distinct entities was supported by double labelling of chromatin with CldU and IdU, respectively, at early and late S-phase and subsequent cultivation of corresponding cells for 5-10 cell cycles before fixation and immunocytochemical detection. This scheme yielded segregated chromatid territories with distinctly separated subchromosomal foci composed of either early- or late-replicating chromatin. The size range of subchromosomal foci was similar after shorter (2 h) and longer (16 h) labelling periods and was observed in nuclei of both living and fixed cells, suggesting their structural identity. A possible functional relevance of chromosome territory compartmentalization into subchromosomal foci is discussed in the context of present models of interphase chromosome and nuclear architecture.

Bromodeoxyuridine↗
PubMed1998

In situ detection of a fungal glycoprotein-elicitor in stem rust-infected susceptible and resistant wheat using immunogold electron microscopy.

Immunoelectron microscopy (IEM) was used to analyze the compatible and incompatible host-pathogen interaction between the obligate, biotroph stem rust (Puccinia graminis f.sp. tritici; Pgt) and primary leaves of wheat (Triticum aestivum L.). The investigation was focused on the subcellular localization of a fungal elicitor glycoprotein of stem rust (Pgt-elicitor). Uredospores as well as fungal infection structures of stem rust on wheat leaves were probed with a specific monoclonal antibody, in order to determine the in situ distribution pattern of the antigen. Binding to the anti-elicitor antibody was observed over the cell wall and the germ pore of germinating uredospores. Immunogold staining was found over the infection structures of stem rust within the wheat leaf tissue of both the compatible and incompatible plant-pathogen interaction. Distinct cell wall layers of the intercellular mycelium, of the haustorial mother cells, as well as of the haustoria were clearly labeled. Gold particles were also detected over the intercellular space and the extrahaustorial matrix in between the extrahaustorial membrane and the haustorial cell wall which indicated a release of elicitor molecules from the fungal cell wall. No labeling was observed over the host cell cytoplasm of the compatible and incompatible interaction, respectively. The immunocytochemical detection of elicitor epitopes over the hyphal cell walls of in vitro grown axenic cultures of P. graminis f.sp. tritici confirmed the occurrence of elicitor molecules in young hyphal material. Elicitor molecules were released by the hyphae of axenic cultures of stem rust in vitro.

Basidiomycota↗
PubMed1998

Enrichment of human bone marrow mononuclear phagocytes and characterization of macrophage subpopulations by immunoenzymatic double staining.

In order to isolate and enrich bone marrow mononuclear phagocytes, we performed magnetic-activated cell sorting using beads coupled to a monoclonal antibody directed against the monocyte/macrophage surface molecule CD14. Colocalization of antigens in single cells was achieved by combining an alkaline phosphatase-anti-alkaline phosphatase and an avidin-biotin complex immunoassay, avoiding the use of peroxidase. Bone marrow macrophages were first labelled by the monoclonal antibody PG-M1 (anti-CD68). Subsequently, cytoplasmic and/or surface double staining by the monoclonal antibodies against HLA-DR and Mac-2 antigen or the lectin GSA-I-B4 was carried out. Whereas HLA-DR was co-expressed by the great majority of PG-M1+ macrophages (84.9%+/-6.9%), only a subpopulation exhibited Mac-2 (69.9%+/-5.9%) antigen or galactoside structures detected by GSA-I-B4 (65.0%+/-6.7%). The latter result differed only slightly from the percentage of GSA-I-B4+ macrophages determined in a previous comparative immunomorphometrical study. Therefore, using our method of isolation and enrichment by magnetic-activated cell sorting, only a negligible portion of macrophages is apparently stimulated, as shown by GSA-I-B4 staining. This methodology seems to be a valuable tool for further studies on the monocyte-macrophage system.

Antigens, CD↗
PubMed1998

Pantoprazole 20 mg is effective for relief of symptoms and healing of lesions in mild reflux oesophagitis.

AIM: To investigate the efficacy of a low dose of pantoprazole, a gastric proton pump inhibitor, for the relief of symptoms and healing of lesions in mild gastro-oesophageal reflux disease (GERD), and to compare it with the efficacy of ranitidine. METHODS: Patients with endoscopically established GERD (Stage I, Savary-Miller classification) were enrolled into a randomized, double-blind, parallel-group and multicentre study (intention-to-treat n = 209, age range 19-82 years). They were treated once daily with oral pantoprazole 20 mg or ranitidine 300 mg, for up to 8 weeks. End-point parameters included relief of symptoms (heartburn, acid regurgitation, pain on swallowing) and the healing of GERD lesions. Relief from symptoms was assessed after 2 and 4 weeks, and endoscopically confirmed healing of lesions after 4 and 8 weeks. RESULTS: The proportion of patients reporting complete relief from symptoms after 2 weeks was greater in the pantoprazole than in the ranitidine group (69 vs. 48%, P < 0.01), with further improvements seen in the pantoprazole group after 4 weeks (80 vs. 65%, P < 0.05, Cochran-Mantel/Haenszel test). Healing of lesions was confirmed in 70/87 (80%) patients after 4 weeks (pantoprazole group), as compared with 55/86 (64%) patients (ranitidine group) (P < 0.05, per protocol population); after 8 weeks the respective results were 78/87 (90%) and 63/86 (73%) patients (P < 0.01). Both study medications were well tolerated. CONCLUSION: Low-dose pantoprazole (20 mg) is clinically superior to ranitidine (300 mg) in providing fast relief from symptoms and healing of lesions in patients with mild GERD.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Prevalence of the C282Y and H63D mutations in the HFE gene in patients with hereditary haemochromatosis and in control subjects from Northern Germany.

Mutation analysis was performed for two HFE mutations (C282Y, H63D) in unrelated patients with hereditary haemochromatosis (n = 92), family members of patients (n = 34), and unrelated controls (n = 157) from Northern Germany, 87/92 patients (94.6%) revealed the C282Y mutation in homozygous form, five were heterozygous. No H63D mutation was found in 174 chromosomes of patients homozygous for C282Y, whereas four of the heterozygote patients also carried the H63D mutation. Among the control group, 9.6% were heterozygotes for C282Y. 2/157 subjects were homozygous, 37/157 were heterozygous for the H63D mutation, but showed no signs of iron overload.

Adult↗
PubMed1998

Increased nuclear traffic chaos in hyphae of Aspergillus nidulans: molecular characterization of apsB and in vivo observation of nuclear behaviour.

Filamentous fungi are model microorganisms for studying nuclear migration in eukaryotic cells. Two genes, apsA and apsB (=anucleate primary sterigmata), were identified in Aspergillus nidulans that affect nuclear distribution in hyphae and specifically block conidiophore development at the metula stage when mutant. Here we describe the cloning, sequencing and molecular analysis of apsB. The gene encodes a 121 kDa coiled-coil, hydrophilic protein that was localized in the cytoplasm. No protein-protein interaction was detected between ApsB and ApsA, a membrane-associated, previously identified protein. An apsB null mutant was characterized by video epifluorescence microscopy using strains that express green fluorescent protein (GFP) in nuclei. With this novel approach, we have discovered a new mutant phenotype and have found that nuclei display an increased chaotic movement in older hyphal compartments that results in clustering and an uneven distribution of these organelles. These results suggest a regulatory role of ApsB in nuclear migration.

Amino Acid Sequence↗
PubMed1998

Effect of IFN-alpha on normal human hematopoiesis: an immunohistochemical and morphometric study on trephine biopsy specimens.

To elucidate the effects of interferon-alpha (IFN-alpha) on normal human bone marrow in vivo, an immunomorphometric study was performed using trephine biopsy specimens without hematopoietic pathology. Samples were derived from patients with mycosis fungoides but no marrow involvement, who were undergoing low-dose IFN-alpha treatment. Parameters included density of reticulin (argyrophilic) fibers, CD61+ megakaryocytes, PGM1+ macrophages, the GSA-I lectin-expressing (activated) macrophage subpopulation, proliferative activity (PCNA staining), and apoptosis. Following IFN-alpha therapy (3 x 3 x 10(6) U/week between 6 and 21 months), morphometric evaluation of sequential bone marrow examinations revealed a significant increase in the number of megakaryocytes and the amount of reticulin fibers. Additionally, there was an overall decrease in PCNA+ cells, accompanied by a reduction in the incidence of apoptotic bodies. On the other hand, total number of macrophages and their activated subfraction remained unchanged. Opposed to in vitro findings, a fibrogenetic capacity of IFN-alpha associated with megakaryocyte growth was detectable. Moreover, contrasting with effects of IFN-alpha treatment in chronic myelogenous leukemia, the incidence of apoptosis was significantly reduced. This feature was assumed to contribute to a maintenance of steady-state hematopoiesis expressed by a nonaltered bone marrow cellularity in our specimens.

Biopsy↗
PubMed1998

Impact of clinical and morphological variables in classification and regression tree-based survival (CART) analysis of CML with special emphasis on dynamic features.

To determine parameters of predictive value in CML, a retrospective clinico-pathological study was performed. This included laboratory data and (pretreatment) bone marrow biopsies of 120 patients with a monotherapy by busulfan (BU) and 50 patients with interferon-alpha 2b (IFN) treatment. Median survival in the BU group was 39 months and in the IFN-treated patients 65 months. Morphological features (CD61-positive megakaryocytes, argyrophilic fibres, pseudo-Gaucher cells) were evaluated by morphometry. Additionally, we measured the incidence of apoptosis (in situ end-labelling technique) and the expression of the proliferating cell nuclear antigen (PCNA). The ratio between the proliferative and apoptotic cell fraction was coined leukaemia turnover index (LTI). In order to estimate the impact of clinical and various morphological as well as dynamic features of prognostic significance, a multivariate analysis was carried out using the classification and regression tree approach (CART). Discrimination of single disease parameters revealed that fibrosis remained the most significant variable for survival in both therapeutic groups. Indicators of myeloid metaplasia such as occurrence of erythro-normoblasts and/or splenomegaly were important clinical parameters for prognosis. Inclusion of morphological as well as dynamic disease features in risk classification resulted in a substantial improvement of prognostic efficiency compared to other predictive scores which could be demonstrated by means of ROC-analysis.

Adult↗
PubMed1998

The impact of mammography quality improvement legislation in Michigan: implications for the National Mammography Quality Standards Act.

OBJECTIVES: This study examined the impact of state legislation on mammography quality and access in Michigan. METHODS: The impact of state legislation was analyzed with respect to utilization, numbers of machines and facilities, and image quality. RESULTS: The legislation had a positive effect on image quality improvement, had no impact on utilization by women aged 50 years and above, and resulted in few facility closures. CONCLUSIONS: Michigan's legislative intervention appears to have had a positive effect on efforts to improve mammography quality assurance with implications for other federal and state efforts to achieve quality assurance in health care delivery.

Aged↗