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Biomedical subjects

A Burkhardt

Publications and source records attributed to A Burkhardt.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of tyrosine kinase activation by mitogenic and nonmitogenic anti-IgD antibodies.

Low concentrations of anti-Ig dextran conjugates that stimulate very high levels of B cell proliferation and Ig secretion stimulate no detectable increases in tyrosine phosphorylation. To study this point further, we compared tyrosine phosphorylation patterns induced by mitogenic and nonmitogenic anti-Ig antibodies. Whereas the mitogenic, strongly cross-linking, antibody H delta a/1 induced greater levels of tyrosine phosphorylation than did the nonmitogenic antibody FF1-4D5, the pattern of substrate phosphorylation was equivalent. At lower concentrations of H delta a/1, which were still mitogenic, the degree of phosphorylation that was induced was similar to that induced by high concentrations of FF1-4D5. Both antibodies stimulated comparable increases in the kinase activity of the three src-related kinases present in normal B cells and linked to the IgR, i.e., Blk, Fyn, and Lyn. These results suggest that the extent of tyrosine kinase activation is proportional to mIg cross-linking, that induction of B cell DNA synthesis may require little tyrosine kinase activation, and that activation of tyrosine kinase per se does not necessarily lead to B cell DNA synthesis.

Animals↗
PubMed1992

Apoptotic cell death and tissue remodelling during mouse mammary gland involution.

During post-lactational mammary gland involution, the bulk of mammary epithelium dies and is reabsorbed. This massive cell death and tissue restructuring was found to be accompanied by a specific pattern of gene expression. Northern blot analysis showed that weaning resulted in a dramatic drop in ODC, a gene involved in synthesis of a component of milk, and the nearly simultaneous induction of SGP-2, a gene associated with apoptotic cell death. These changes were followed by decreases in expression of milk protein genes to basal levels and expression of genes associated with regulation of cell proliferation and differentiation, p53, c-myc and TGF-beta 1. Subsequently, additional genes implicated in stress response, tissue remodelling, and apoptotic cell death were transiently expressed, expression peaking at about 6 days post-weaning. A non-random degradation of DNA yielding the oligonucleosomal length fragmentation pattern typical of apoptotic cell death (Wyllie, 1980; Wyllie et al., 1980) was detected in association with morphological changes and gene expression. The correlations between: (a) changes in morphology, (b) pattern of gene expression and (c) changes in DNA integrity suggest that complementary programs for cell death and tissue remodelling direct post-lactational mammary gland involution.

Animals↗
PubMed1992

Intraepithelial lymphocytes and Langerhans cells in the oral mucosa--dynamic aspects.

In the oral epithelium a constant population of non-epithelial immunocompetent cells--lymphocytes and Langerhans cells exists. 3025 such cells of the murine and 542 of the normal human oral mucosa were documented photographically at the ultrastructural level. Location within the epithelium, morphological signs of locomotion, membrane configuration and labeling of the intercellular substance by ruthenium red were registered. About 40 per cent of the lymphocytes and 70 per cent of the Langerhans cells show signs of locomotion, predominantly in a lateral and basal direction. Occasional cells crossing the basal lamina are seen. Close apposition, or rarely a denticulated surface and lysis of desmosomes were present, both probably indications of cellular interactions. Ruthenium red labeling of the glycocalix is continuous forming a homogeneous layer between epithelial and non-epithelial cells and between intraepithelial cells, suggesting an even distribution of antigens and the lack of preformed spaces for intraepithelial cells. Murine and human intraepithelial cells exhibited no major differences.

Animals↗
PubMed1992

[The color and structure of the human iris. 2. Studies of 200 twins].

Subject of the present report is an investigation of the heredity of 30 iris characteristics. The material basis of this sample of twins (100 monozygotic and 100 dizygotic pairs), the largest ever taken as a basis for the purpose of iris research, consists of standardized colour photographs of the examined persons' irises and iris-microscopic observations. The pairs of twins are compared to 100 non-related casual pairs in order to render a better estimation of the degree of heredity of the features possible. On every occasion several classes were constituted for the concordance verification. These classes result from the number of the classes of the forms of markedness and present different levels of similarity. The different distribution of the twin pairs and the control pairs on the concordance classes are always examined for their statistical significance, and for each group of pairs a concordance value is computed. The intervals between the concordance values of the monozygotic and dizygotic pairs and the control pairs indicate the degree of heredity of the investigated feature. Taking all the compiled factors and conditions into consideration, an evaluation of the features as heredity features is made. Though a hereditary component can be observed for all iris characteristics, only about a third could be called heredity features. Quantity of pigment and the hitherto undescribed limiting layer folds were evaluated as "very good", whereas pigment colour in the fine analysis, quality of the anterior stroma leaf, frequency of iris crypts and iris frill position were judged as "good". Tone of blue, markedness of Woelfflin nodules, quantity and markedness of contractional rings could be evaluated as "moderately good" as to their heredity. On the basis of the prior concordance investigations for each of the 300 pairs, a "similarity index" and a "concordance index" were computed in order to arrive at evidence as to the degree of similarity of the single pairs; i.e. in order to detect the limits of the similarity between non-identical twins and the dissimilarity between identical twins. This concluding investigations lead to the question of the possibility of a diagnosis of genetic identicalness solely on the basis of the comparison of irises.

Adolescent↗
PubMed1992

[The color and structure of the human iris. 1. Morphological studies].

The material basis of this investigation consists of empirical findings and colour photographs of the irises of 200 pairs of twins and 100 control pairs. For the morphological investigation first-born twins and control persons are combined to constitute a comparative group of 400 non-related testees. Research by means of the iris microscope and the evaluation of standardized iris photographs led to the development of a catalogue of features which describes 10 iris characteristics for the iris colour and 20 for the iris structure. For each feature different degrees of markedness are defined and their frequency is determined. Similarly, intraindividual right/left and sex differences as well as age-dependencies and the relation between the features are examined. The setting-up of features includes outlining an iris-colour class system in order to render a better and more practicable determination of eye colour possible. As a substitute for Martin/Schulz's table of eye-colour, which describes only eye-colour phenomena, 4 iris-colour classes are set up whose main criterion of classification is the quantity of pigment. When we consider the testees of all age classes, sex differences have no statistical relevance as for iris colour. Only in the case of male testees may an intensive decrease of blue and brown iris colour in favour of combination colours (yellow pigment colours in particular) be observed during the phase of puberty. Therefore, the brightening postulated in the relevant literature can be confirmed. With regard to female testees, in contrast, pigment shifting is of no statistical relevance. After a slight brightening the irises numerically re-darken at the adult-stage to the initial child level, i.e. they become "dark again" rather than just become "darker". Within the iris structure only the characteristics of the anterior stroma leaf show sex differences. They are, however, only weakly marked and can be described merely as a trend. Over the whole range of the age classes, there are no outstanding structural differences. The different iris characteristics concerning iris colour stand in a significant relation to each other. When we consider the statistically relevant relations between structural features, it becomes clear that particularly reduced and particularly intact iris characteristics correlate. Thus, we can distinguish between an intact type of iris and a reduced one. Three quarters of the testees, however, combine reduced and intact properties with medium degrees of markedness.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1991

Pulmonary toxicity of the combination of bleomycin and peplomycin--an experimental study in rats.

Combination of the two drugs bleomycin (BLM) and peplomycin (PEP) may enhance their antineoplastic effects; however, it is not known as to whether this enhancement is accompanied by a concomitant increase in toxicity, especially toxic lung damage. A histologic and stereologic investigation was carried out to compare the pulmonary toxicity of BLM, PEP, and a combination of the two drugs in animals. A total of 180 female Wistar rats were randomly assigned to 4 groups: 45 animals were treated with daily i.p. injections of 4 mg/kg BLM, 45 rats received 2.5 mg/kg i.p. PEP daily, 45 animals were given i.p. injections of a combination of 2.5 mg/kg BLM and 1 mg/kg PEP, and 45 rats received 1 ml 0.9% NaCl solution. Histological examination of the lungs demonstrated varying degrees of exudative and fibrosing alveolitis in animals treated with BLM, PEP, and BLM-PEP. Stereological analysis revealed a significant thickening of the alveolar wall after 20-60 days and a significant decrease in the surface density of alveolar walls after 40-60 days in all treated groups. Both histological examination and stereological parameters indicated more pronounced inflammatory changes in the alveolar walls and a prior loss of alveolar surface after 20 and 30 days in animals receiving PEP and PEP-BLM as compared with those undergoing BLM treatment. After 40-60 days, during which time irreversible fibrotic changes prevailed, significant stereological differences between the three treated groups could not be detected. Thus, our experimental observations did not show any potentiation of the toxic pulmonary effect of BLM and PEP following their combined administration.

Animals↗
PubMed1991

Prevention of bleomycin-induced fibrosing alveolitis with indomethacin: stereological studies on rat lungs.

The prevention of the pulmonary toxicity of bleomycin (BLM) has been investigated in experimental models where pulmonary damage was induced with one intra-tracheal dose of BLM. The present investigation was carried out as a pre-clinical study in which BLM was administered systemically. The non-steroid anti-inflammatory drug indomethacin (INDO) was chosen as a possible candidate for pulmonary protection. Twenty female Wistar rats were treated daily with 4 mg/kg (7.3 units) BLM intra-peritoneally for 50 days and 20 rats with BLM and with 1 mg/kg INDO subcutaneously for 62 days. There were 20 animals as controls. Histological examination revealed fibrosing alveolitis in the BLM-treated group which was markedly suppressed in the combination group. Quantitative morphological (stereological) parameters demonstrate that BLM induced alveolar wall thickening (+45%), pulmonary fibrosis (+110%), and an increase of alveolar wall nuclei and of intra-alveolar macrophages (volume densities +43% and +133%, P less than 0.001). In contrast, after combination with INDO significant differences to the control group could not be detected except for a slight increase of intra-alveolar macrophages (+62%). Thus, INDO is a highly efficient agent in the prevention of BLM-induced pulmonary damage.

Animals↗
PubMed1979

Alveolitis due to hair-spray. Ultrastructural observations in two patients and the results of experimental investigations.

Observation of two patients with hair-spray induced lung disease have prompted us to study the ultrastructure of the lung lesion. We have compared the results with experimental lesions in animals injected with hair-spray extracts and with human monocyte cell cultures exposed to hair-spray. The lungs show a chronic alveolitis with a striking granulomatous reaction including macrophages and multinucleated giant cells of the foreign body type. The intraalveolar and interstitial macrophages and the giant cells all contain PAS-positive material. Ultrastructurally distinct lamellar inclusions are found in the secondary lysosomes of the macrophages and giant cells. Identical structures can be produced in animals injected with hair-spray extracts and with polyvinyl-pyrrolidone and -acetate (PVP/PVA), which are regular ingredients of hair-sprays. Large, presumeably polymeric particles (PVP/PVA) are ingested by giant cells. This "gigantophagocytosis" is associated with the fusion of mononuclear phagocytes and leads to the genesis of giant cells. In cell cultures of human blood monocytes hair-spray extracts and PVP/PVA induce maturation and aggregation of these cells, with PAS-positive cytoplasmatic inclusions. The development of multinuclear giant cells in these monocyte cell cultures is also seen. These observations suggest that hair-spray induced lung disease is caused by the prolonged and extensive body response of the local mononuclear phagocyte system (MPS). Overstimulation of the MPS leads to a quantitative and qualitative change which is followed by a partial blockade of this system. The alveolitis is a consequence of the foreign body response to inhaled hair-spray substances.

Female↗
PubMed1979

Plasma cells and immunoglobulin-synthesis in oral precancer and cancer. Correlation with dysplasia, cancer differentiation, radio- and chemotherapy.

The subepithelial and peritumoral inflammatory infiltrates of 202 oral premalignant and malignant lesions -- 108 leukoplakias and 94 squamous cell carcinomata with different grades of dysplasia were examined using an immunoenzymatic method. In addition, the influence of radiation and bleomycin-therapy on the stromal reaction of 24 carcinomata was studied. The incidence of immunoglobulin labelled plasma cells (IgA and IgG) was twice as high in those cases of leukoplakia where dysplasia was present. The number of plasma cells, especially IgA- and IgG-containing plasma cells, decreased significantly with progressive tumor dedifferentiation. The plasma cell response differed before and after radiation with a decrease in IgA- and IgG-containing plasma cells after therapy. In contrast, bleomycin-therapy did not produce distinct changes in the humoral and cellular stromal reaction. In the epithelium, IgA and IgG were localized throughout all epithelial layers in leukoplakias with dysplasia. This finding indicates a leakage of locally synthesized immunoglobulins through an altered oral mucosa. This investigation reveals alterations in the local immune homoeostasis of the oral mucosa in premalignant and malignant lesions which varies with the grade of dysplasia, tumor differentiation and therapy.

Bleomycin↗
PubMed1977

Giant cell stromal reaction in squamous cell carcinomata. Electronmicroscopic and ultrahistochemical observations on the genesis and functional activity of multinucleated giant cells in bleomycin-induced tumor regression.

Ten cases of oral squamous cell carcinoma, treated by bleomycin, were studied by electron microscopy with particular regard to the stromal reaction. The genesis and phagocytic function of multinucleated giant cells of foreign body type were observed. These cells phagocytize devitalized, keratinized tumor cells in particular. Their genesis from monocytic macrophages and endocytosis of large keratinized tumor cells are described in detail. Both phenomena are connected and the mode of formation of the cells results in functional specialization. The initial stages of intracellular digestion do not seem to take place within membrane limited vacuoles but in specialized cytoplasmatic areas which are formed around the ingested material. These contain high concentrations of hydrolases, sealed off from the rest of the cell by a clear zone of organell-free cytoplasm. This unique form of phagocytosis and digestion ("gigantophagocytosis*) is only possible in these highly specialized giant cells and explains their biological significance. It is likely that secondary lysosomes are formed in subsequent stages of digestion. The difference between our results and the experimental observations of other authors are discussed.

Bleomycin↗
PubMed1977

Unusual obliterative disease of the hepatic veins in an infant.

Hepatic fibrosis with obliterative lesions of the small hepatic veins occurred in a three month old infant with fatal congenital leukaemia treated with cytostatic drugs. The vascular changes were characterized by an unusual, hitherto unreported angiomatoid, proliferation of the endothelium. The process is compared with the more common subendothelial-fibrous type of the "veno-occlusive disease". An etiological interpretation is difficult, possibly the process is a secondary reaction to the endothelial to a cytostatic-induced lesion with hepatic fibrosis.

Antineoplastic Agents↗