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Biomedical subjects

H Sauer

Publications and source records attributed to H Sauer.

At least 217 records · Page 12Linked to original sources
PubMed1991

Complement pore genesis observed in erythrocyte membranes by fluorescence microscopic single-channel recording.

The formation and opening of single complement pores could be directly observed in erythrocyte ghosts by confocal laser-scanning microscopy employing the recently introduced method of fluorescence microscopic single-channel recording. Resealed sheep erythrocyte ghosts were incubated with human complement. By limiting the concentration of C8, the eighth component of complement, the fraction of cells rendered permeable for the small polar fluorescent probe Lucifer Yellow was varied between 0.50 and 0.90. Under each condition the flux rate, k, of Lucifer Yellow was determined for a substantial number of ghosts. By analysing the sample population distribution of k the flux rate k1 of ghosts with a single pore was found to be (4.8 +/- 1.1) x 10(-3) s-1 consistent with a pore radius of about 3.5 nm (35 A). The genesis of single complement pores was studied by continuous influx measurements while triggering pore formation by a temperature shift. Pore genesis was found to be a very slow process, proceeding on a time scale of several minutes. During pore genesis the influx curves had a sigmoid shape, which excluded the possibility that the pore was preformed on the membrane surface and subsequently inserted. However, the influx curves could be well simulated by a model which assumed that pores grow stepwise by sequential incorporation of C9 monomers. The model predicts conditions under which the incorporation of single monomers can be directly revealed.

Animals↗
PubMed1991

A microassay for the pore-forming activity of complement, perforin, and other cytolytic proteins based on confocal laser scanning microscopy.

A fluorescence microscopic assay for the activity of complement, perforin, and other cytolytic proteins which form transmembrane pores in cellular membranes is described. The assay was worked out and tested with red blood cell membranes (ghosts) and was then applied to intact hemoglobin-free cells. Resealed human erythrocyte ghosts were incubated with complement or perforin. A small polar fluorescent probe (fluorescein-labeled 1-kDa dextran, FD1) which permeates through complement and perforin pores but not through normal cell membranes was added to the samples. The capability of the confocal laser scanning microscope (CLSM) to generate thin optical sections was exploited to visualize and quantitate fluorescence inside single ghosts and thus determine the fraction of ghosts which had become permeable for FD1. The activity of complement or perforin was quantitated by plotting the fraction of permeable cells versus the concentration of the pore-forming protein. The results were in good agreement with those of a conventional hemolytic assay. The CLSM-based assay was then applied to intact hemoglobin-free cells for which only few alternative assays are available. Compared to conventional hemolytic assays for the activity of pore-forming proteins the assay described here can be applied to a large variety of natural and artificial membrane systems. The assay can be performed under nonlysing conditions. Furthermore, the assay is simple, relatively fast, and requires only extremely small amounts of cells and pore-forming proteins.

Animals↗
PubMed1991

Functional size of complement and perforin pores compared by confocal laser scanning microscopy and fluorescence microphotolysis.

Confocal laser scanning microscopy and fluorescence microphotolysis (also referred to as fluorescence photobleaching recovery) were employed to study the transport of hydrophilic fluorescent tracers through complement and perforin pores. By optimizing the confocal effect it was possible to determine the exclusion limit of the pores in situ, i.e. without separation of cells and tracer solution. Single-cell flux measurements by fluorescence microphotolysis yielded information on the sample population distribution of flux rates. By these means a direct comparison of complement and perforin pores was made in sheep erythrocyte membranes. In accordance with previous studies employing a variety of different techniques complement pores were found to have a functional radius of approx. 50 A when generated at high complement concentrations. The flux rate distribution indicated that pore size heterogeneity was rather small under these conditions. Perforin pores, generated in sheep erythrocyte membranes at high perforin concentrations, were found to have a functional size very similar to complement pores. Furthermore, the functional size of the perforin pore seemed to be relatively independent of the dynamic properties of the target membrane since in two cell membranes which are very different in this regard, the human erythrocyte membrane and the plasma membrane of erythroleukemic cells, the functional radius of the perforin pore was also close to 50 A. A perforin-specific antibody reduced the functional radius of perforin pores to 45 A.

Animals↗
PubMed1991

[Therapy studies in medical oncology. Analysis of progress-- Usefulness for the individual patient].

Since the end of the nineteen-forties, medical oncologists have been using cytostatic drugs and, in the case of some tumors, hormone-active substances. To these have been added in recent years, although only for a few indications, the so-called biological response modifiers (BRM substances) such as interferons and interleukins. New substances and methods are accepted into routine practice only after well-documented clinical trials. This development is, however, far from being complete; there continues to be a requirement for new standards and an optimisation of indications, dosages, drug combinations, modes of administration, and intervals between dosages. On the basis of a number of studies, it is shown how, building on the experience obtained in earlier trials, the curative and palliative effects of such treatments can be improved. In the palliative situation, in particular, the indication and nature of chemotherapy must be reconsidered since most earlier studies failed to document the factor "quality of life".

Adult↗
PubMed1991

Improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas: updated report on 65 patients.

From July 1986 to 1990, 65 patients with deep-seated, advanced sarcomas (43 soft-tissue sarcomas, 12 Ewing's sarcomas, 7 chondrosarcomas and 3 osteosarcomas) were entered in a protocol involving regional hyperthermia (RHT) combined with systemic ifosfamide and etoposide. RHT was produced by an electromagnetic deep regional heating device (BSD Medical Corporation, Salt Lake City, Utah). Of these patients, 62% (40 patients) had received ifosfamide-containing drug regimens before entering the RHT study, 26% (17 patients) were pretreated by surgery and/or radiation and 12% (8 patients) were treated primarily. A total of 426 RHT treatments (mean 6.6 RHT/patient) were applied predominantly within the pelvic region (82%) bearing relative large tumours (mean volume 500 cm3). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1-5), etoposide (100 mg/m2, days 1, 3, 5) and 2-mercaptoethanesulphonic acid (mesna; 300 mg/m2 x 4, days 1-5) with RHT only given on days 1 and 5 in repeated cycles every 4 weeks. Detailed thermal mapping by invasive thermometry was performed in all patients. In 61 patients evaluable for tumour control the overall objective response rate including 9 complete responders (CR), 4 partial responders (PR) and 8 patients with favourable histological response (FHR) was 34% (95% confidence limits, 23%-46%). Following CR, the patients are alive and remain disease-free (mean disease-free survival 15.6 months). Of the patients with PR and FHR, 3 died from metastatic and/or local disease after 4, 17, and 39 months, and 1 patient died from other disease (acute myelocytic leukemia) after 27 months. The other 8 patients remain stable at 29, 25, 17, 11, 10, 8, 7, and 6 months. Twenty-two patients revealed no change and 18 patients showed local tumour progression (PD). Side-effects of RHT were tolerable and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. By analysis of temperature parameters, the time-averaged temperatures of all RHT treatments calculated for 20% (T20), 50% (T50) or 90% (T90) of measured tumour sites differed significantly between responders (CR + PR + FHR) and non-responders (PD), respectively (T20, P = 0.001; T50, P = 0.0005; T90, P = 0.0001). the data further support a strong potential for ifosfamide plus etoposide combined with RHT in pretreated patients with advanced sarcomas.

Adolescent↗
PubMed1991

Neurological soft signs in schizophrenia.

A new scale for neurological soft signs (NSS) was constructed and consists of 17 items compiled from the literature. The scale was found to have a high internal reliability (Cronbach's alpha 0.83) and a high interrater reliability (0.88). According to the results of a factor analysis, NSS are covered by five factors: 'motor coordination', 'integrative functions', 'complex motor tasks', 'righ/left and spatial orientation' and 'hard signs'. Using this scale, the associations of NSS with clinical course and brain alterations were investigated. NSS varied with the clinical course and were significantly correlated with some BPRS subscales, in particular 'thought disorder'. In addition, the 'motor coordination' soft signs were found to correlate with morphological alterations in the basal ganglia.

Adult↗
PubMed1991

[Determination of lymphocyte subpopulations and their activation status in patients with rheumatoid arthritis treated with plasma exchange and pulse therapy].

In patients with systemic rheumatoid arthritis (RA) and extraarticular manifestation treated with plasma exchange or prednisolute-pulse-therapy, respectively, and followed by an additional immunosuppression by cyclophosphamide we have assessed the lymphocyte subpopulations of the peripheral blood and the cells expressing activating markers by means of monoclonal antibodies using fluorescence microscopy or fluorescence flow cytometry. Before therapy the patients showed a very different level of lymphocyte subpopulations tested. During treatment in both groups of patients there was not any uniform tendency in CD3, CD4 and CD8 positive cells. The percentage of activated lymphocytes was initially elevated and we found significant reduction, mainly in the 4th week after starting of therapy. Following in the most cases the level recovered to the state before therapy. For the single patients an individual pattern of reaction was evident in relation to the initial position before treatment.

Arthritis, Rheumatoid↗
PubMed1991

[Circulating lymphocyte subpopulations in patients with Crohn's disease].

Circulating lymphocytes were enumerated in 25 patients with Crohn's disease and in 43 healthy donors by immunofluorescent staining using monoclonal antibodies for T cell surface phenotypic markers (CD 3, CD 4, CD 8) or for surface immunoglobulin of B cells (mu-chain). Proportions of peripheral T cells and percentages of T cell subsets in Crohn's disease were not significantly different from those in controls. For analyzing the lymphocytes for the expression of activation associated antigens (HLA-DR, CD 25) we found increased numbers of activated lymphocytes during acute exacerbation, whereas, in remission, the population of activated lymphocytes was in the upper normal range. The results leads to the conclusion that the assessment of activated lymphocytes may serve as a parameter in the evaluation of the activity of Crohn's disease.

Adolescent↗
PubMed1991

[Bicycle accidents of children].

Bicycles are funny and stimulating sport and play tools for children but riding a bicycle brings also a lot of risks. The most frequent causes of injuries, the accident patterns, the seriousness and patterns of injuries were examined by means of two investigations of 823 children injured in bicycle accidents. The safety consciousness of children and parents was evaluated as well. Three sources of danger were found to be the most frequent causes of accidents: "the agent" (bicycle), "the environment" (situations) and "psychodynamic risk factors" (behaviour). Prevention measure for all three sources of danger will be discussed. The use of bicycle helmets as simple, cheap and efficient protective measure is recommended in particular.

Adolescent↗
PubMed1990

Transients of perforin pore formation observed by fluorescence microscopic single channel recording.

A new type of single channel recording is described. Large pores were generated in the membranes of resealed human erythrocyte ghosts by incubation with perforin (cytolysin). The flux of the polar fluorescent probe Lucifer Yellow was measured in single ghosts by the fluorescence microphotolysis (photobleaching) technique. The distribution of flux rates for ghosts treated with a limiting perforin concentration showed equidistantly spaced peaks suggesting that subpopulations of ghosts with 0, 1 and 2 pores were resolved. Furthermore, distributions obtained for very different perforin concentrations could be well simulated by using one common value for the flux rate of the single pore (k = 4.65 x 10(-3) s) and assuming a Poisson distribution of pores among ghosts. The flux rate of the single pore corresponds to a pore radius of approximately 50 A, a value which is much smaller than that obtained previously by electron microscopic studies but which agrees well with recent electrical single channel recordings. Mature perforin pores were observed to be very stable. No closing events were detected at a time resolution of 0.2 s for a wide range of temperatures and Ca2+ concentrations. However, the formation of new pores was an unexpectedly slow process. Fluorescence microscopic single channel recording as introduced by this study is applicable to a variety of cellular systems and fluorescent probes and thus may complement the information obtainable by electrical single channel recording of anorganic ion fluxes.

Erythrocyte Membrane↗
PubMed1990

On the validity of the German version of the Comprehensive Psychopathological Rating Scale.

The construct validity of the German Version of the Comprehensive Psychopathological Rating Scale (CPRS) was investigated in a longitudinal study on 60 hospitalised RDC-schizoaffective patients. The validation included tests of hypotheses about means in crosssection and, in therapy, the course of schizoaffective psychoses. Thus, it is assumed that differences in diagnosis (RDC-schizodepressives versus RDC-schizomanics) are reflected by significantly higher scores on the respective subscales of the CPRS. Furthermore, the subscales of the CPRS should be sensitive to therapeutic change. In addition, correlations were tested using instruments of similar or different validity claim (Hamilton Depression Scale, Mania Rating Scale, Brief Psychiatric Rating Scale). All hypotheses about means could be confirmed. The convergent and discriminant validity of the CPRS is discussed on the basis of multiple-indicator matrices computed for each of the three points of measurement.

Adult↗
PubMed1990

Philadelphia chromosome-negative acute hematopoietic malignancy: ultrastructural, cytochemical and immunocytochemical evidence of mast cell and basophil differentiation.

We describe a patient with fever and multiple osteolytic bone lesions accompanied by hypercalcemia, a duodenal ulcer, anemia, and thrombocytopenia. Bone marrow showed a dense infiltration by abnormal cells characterized by small basophil granula, erythrophagocytosis and nuclear atypia. These cells were positive for toluidine blue and partly for myeloperoxidase and chloroacetate esterase, expressed myeloid differentiation markers, and exhibited multiple numerical and structural chromosome aberrations. Molecular genetic analysis showed no breakpoint cluster region rearrangement. Electron microscopy demonstrated granula both of basophil and mast cell type. Concluding, in this patient an acute hematopoietic malignancy with many features of malignant mastocytosis but also with signs of a basophil differentiation. This is further support for a hematopoietic stem cell origin of human mast cells.

Adult↗