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Biomedical subjects

J Lorenzen

Publications and source records attributed to J Lorenzen.

108 records · Page 6Linked to original sources

Radiotherapy of the rhabdomyosarcoma R1H of the rat: postoperative radiotherapy.

Rhabdomyosarcoma R1H of the rat was excised aiming for a complete macroscopic local excision. Adjuvant radiotherapy was performed from the third postoperative day on. Former tumor sites were locally irradiated with 200 kVp X rays 4 times per week over a period of 6 weeks. Total doses of 0, 15, 30, 45 and 60 Gy were applied. The tumor volume was measured and the time to regrow to initial volume was assessed. The results were compared to the effect of a standard radiotherapy alone with 30 fractions of 2 Gy applied within 6 weeks. All tumors recurred despite of the irradiation treatment. At high total doses (greater than 30 Gy), adjuvant radiotherapy was found to improve short term tumor response considerably, whereas no positive effect was seen at low doses. After a total dose of 60 Gy and long time intervals after start of treatment, radiotherapy alone and a combination of surgery and radiotherapy seem to be isoeffective in our tumor system.

Animals↗

Megakaryocytes in myelodysplasia: an immunohistochemical study on bone marrow trephines.

Megakaryocytes in 63 bone marrow trephine biopsies were examined for their staining characteristics, location and size distribution using the monoclonal antibody Y2/51 directed against platelet glycoprotein IIIa (CD61). Megakaryocytes in normal bone marrow were evenly distributed and demonstrated homogeneous staining with Y2/51. In addition, there was little variation in their size or shape. In contrast, myelodysplastic and myeloproliferative bone marrow trephines showed considerable dysmegakaryopoiesis demonstrated by heterogeneity of staining, an altered architectural distribution with a predominantly paratrabecular location and considerable variation in size and shape. Furthermore, in myelodysplasia 25% of the CD61 positive cells were micromegakaryocytes as opposed to less than 10% in normal or reactive marrows. Such dysmegakaryopoiesis is believed to be a clinically important feature of myelodysplasia, although until now it has only been possible to assess it subjectively. The availability of the monoclonal antibody Y2/51 provides a rapid and reproducible means of studying megakaryocyte size, shape and distribution in routine trephine specimens and may help to overcome some of the diagnostic problems currently associated with myelodysplasia and other intrinsic bone marrow neoplasias.

Antibodies, Monoclonal↗

Differential effects of LPS, IFN-gamma and TNF alpha on the secretion of lysozyme by individual human mononuclear phagocytes: relationship to cell maturity.

Human mononuclear phagocytes can be activated to perform a variety of complex functions by exposure to the immunomodulators, lipopolysaccharide (LPS), interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF alpha). Although such activation often involves the release of various cytokines by monocytes and macrophages, little is known of the effects of such signals on their secretion of lysozyme (LZM). In this study, a reverse haemolytic plaque assay for LZM secretion is coupled with immunocytochemistry for the pan macrophage (CD68) marker, EBM/11. This enabled the direct effects of LPS, IFN-gamma and TNF alpha on the secretion of LZM by individual, immunoidentified human mononuclear phagocytes to be investigated. The overall secretion of this peptide by populations of freshly isolated or 3-day cultured monocytes was augmented by exposure for 6 hr to bacterial LPS, recombinant human IFN-gamma or recombinant human TNF alpha. Extension of the culture period for monocytes from 3 to 7 days prior to use in the assay resulted in higher levels of LZM secretion, which could be further increased by TNF alpha but not by LPS or IFN-gamma. Individual peritoneal macrophages activated by inflammation in vivo were uniform in their augmented LZM responses to TNF alpha, but a small subpopulation of human peritoneal macrophages, which may represent younger 'inflammatory' exudate macrophages, was seen to be preferentially responsive to the LZM-stimulating effects of LPS and IFN-gamma. These studies suggest that (i) secretion of LZM by human mononuclear phagocytes can be regulated by LPS and IFN-gamma, although the effects of these agents may be dependent upon the state of maturation and/or differentiation of the cells, and (ii) TNF alpha is a potent stimulant of LZM secretion by monocytes and macrophages irrespective of cell maturity.

Cell Differentiation↗

Heterogeneity among human mononuclear phagocytes in their secretion of lysozyme, interleukin 1 and type-beta transforming growth factor: a quantitative analysis at the single-cell level.

Human mononuclear phagocytes have the remarkable capacity to secrete a wide range of products. The reverse hemolytic plaque assay was used to visualize and quantify the secretion of lysozyme, interleukin 1 or type-beta transforming growth factor by individual monocytes and macrophages. With this sensitive immunoassay, the release of these products by either freshly isolated monocytes, macrophages derived from monocytes in vitro, or activated peritoneal macrophages was detected in both the presence and absence of secretagogues. When coupled with immunocytochemistry for EBM/11, a monoclonal marker for human cells of the monocyte/macrophage cell lineage, functional heterogeneity was evident both in the amount of lysozyme, interleukin 1 or type-beta transforming growth factor released per cell, and in the number of EBM/11+ cells which secreted detectable levels of these products at any one time. In addition, there was a size-dependent heterogeneity among human monocytes and culture-derived macrophages in their ability to secrete interleukin 1 or lysozyme, respectively. We conclude that the secretory activity of individual mononuclear phagocytes is markedly heterogeneous.

Antibodies, Monoclonal↗

Mycoplasma infection of cell lines can simulate the expression of Fc receptors by binding of the carbohydrate moiety of antibodies.

During the production of Fc receptor (FcR)-bearing hybridomas it was observed with a particular monoclonal anti-sheep red blood cell antibody (anti-SRBC 1/5, IgG1) that the contamination with Mycoplasma arginini of in vitro cultured cell lines leads to an apparent FcR activity. This property did not correspond with the serological typing since other antibodies of the same isotype could not support FcR rosette formation. Another mycoplasma strain M. orale lacked this property. Analysis of the binding reaction revealed that M. arginini contains a lectin which binds the carbohydrate moiety of the anti-SRBC 1/5 antibody, i.e. anti-SRBC 1/5 synthesized under the influence of tunicamycin or deglycosylated by NaIO4 oxidation did not support rosette formation. These data suggest that binding of antibodies to certain mycoplasma strains may be a pathogenic factor during mycoplasma infections by masking the microorganisms with the host's own defense molecules. The experiments with M. arginini-infected cell lines gain immunological importance since we obtained identical results with staphylococcal protein A, as another bacteriological FcR, and cell lines expressing intrinsic membrane FcR. Although it is an open question whether the glycoconjugates are directly bound by the FcR or else by influencing the three-dimensional structure of the antibodies, it seems possible that FcR in general may be lectins.

Animals↗

Pivmecillinam in the treatment of therapy resistant urinary tract infections. A comparison with pivmecillinam, pivampicillin and their combination.

Pivmecillinam is a new penicillin-like compound belonging to the so-called amidinopenicillins and characterized by a high antibacterial activity against Enterobacteriaceae and by demonstrated synergism when combined with other beta-lactam antibiotics. In this prospective trial geriatric patients with a stationary indwelling catheter and significant bacteriuria caused by Enterobacteriaceae were treated for four weeks with pivmecillinam, pivampicillin or various combinations of the two compounds. Urine specimens were obtained weekly, and in eight patients receiving pivmecillinam 75% of the urine samples were free from Enterobacteriaceae during the period of treatment. The figure was 91% in 24 patients receiving combination therapy. In seven patients treated with an equimolar dose of pivampicillin alone 43% and 23% of the urine specimens, controlled during the first and the second havles of the treatment period respectively, Enterbacteriaceae was eradicated. In this group there was a marked and increasing tendency towards infections caused by more resistant strains of Enterobacteriaceae as the treatment progressed. The latter is keeping with the observation that pivmecillinam, as opposed to ampicillin, apparently does not cause any selection of resistant Enterobacteriaceae in the faecal flora which is the main source of urinary pathogens.

Aged↗

Selective inhibitory effect of porcine follicular fluid on follicle stimulating hormone secretion in anterior pituitary cells in culture.

Incubation of rat anterior pituitary cells in culture with porcine follicular fluid (treated with charcoal to remove steroids) led to a marked inhibition of spontaneous FSH release while no effect was observed on basal LH secretion. The inhibitory effect of follicular fluid was, however, less specific on LHRH-induced gonadotropin release. Although more potent on FSH than LH release, a significant inhibition of LH release induced by the neurohormone was also observed. This inhibitory activity is mainly associated with material of MW greater than or equal to 10,000 daltons.

Animals↗

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling.

In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics.

Acute Disease↗

[Correlation of low back pain and enhanced vascularization in the vertebral endplate].

AIM OF THE STUDY: Degenerative changes of the motion segments are accompanied by an increased vascularization of the endplates. Nerve elements have been demonstrated in the environment of the endplate vessels, which might play a role in pressure related pain sensation. In order to investigate this theory we compared and correlated the extent of memory pain as determined by discography with the amount of vascularization in the endplates on histological examination. METHOD: Discography was performed in 32 Patients (21 female, 11 male), who underwent spinal fusion. The extent of pain sensation was determined on a self reported visual analogue scale ranging from 0-10 Points. Bone chips from the anterior vertebral endplates were obtained during surgery. Decalcified paraffin-embedded samples were then immunostained with the vascular endothelial marker CD 34. The quantification of endothelium as part of the whole cross section area was performed by means of a computerized optical method. RESULTS: The extent of the pain sensation during discography ranged from 0-9 points on the VAS (average: 5.3 points, SD 3.1). On the histological quantification the total endothelial area per observed field varied from 0.04 to 7.39 % (average: 2.19 %, SD 1.62). The comparison of the pain extent on discography and the vascularization of the endplate resulted in a correlation coefficient after Spearman of rho = + 0.64 (p=0.0006). CONCLUSION: The extent of vascularization in the degenerated endplates of a motion segment shows a moderate correlation with the self reported VAS scores after discography. Further investigations will have to clarify, whether neurogenic structures originating from vascular endothelium yield a better correlation to discogenic pain.

Endothelium, Vascular↗

Helping parents to grieve after second trimester termination of pregnancy for fetopathic reasons.

The main interest in our study was to find out if advice given to facilitate mourning after perinatal child loss (looking at the dead child, picture, burial) could be used to help parents terminating pregnancies for fetopathic reasons. To evaluate the acceptance and to compare the outcome in grief reactions we interviewed women undergoing termination of pregnancy for fetopathic reasons 1-2 days after the loss of the child and they answered a mailed questionnaire 8 weeks later. For comparison we assessed data from women with spontaneous child losses within the 12th to 24th week of pregnancy in a similar way. No difference in the extent of creating memories between the two groups of child losses could be assessed (44% of women after termination and 55% after spontaneous loss looked at their dead child). Making the dead baby a tangible person led to stronger grief reactions immediately after the loss without significant difference due to the kind of loss. But 8 weeks later women after spontaneous child losses reported significantly more mourning than those after termination. It could be shown that women do mourn after termination of pregnancy, that creating memories leads to more intense grief reactions shortly after the loss and that grief diminishes over time. The advice given to facilitate mourning after perinatal child loss can be transferred to parents dealing with termination of pregnancy for fetopathic reasons although coping seems to be more complicated in the latter situation.

Abortion, Induced↗