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Biomedical subjects

H Cottier

Publications and source records attributed to H Cottier.

At least 19 recordsLinked to original sources

Novel, contrast gradient-oriented, automated chromatin texture analysis. I. Feasibility study on nuclei from benign and malignant breast epithelial cell lines in fine needle aspirates.

Coarse granularity of nuclear chromatin texture is a prominent feature of most malignant cell lines. We have chosen the abrupt transition from eu- to heterochromatic foci (high contrast gradient [CG]) as a novel parameter for coarseness. This feature was quantified using automated image analysis of single nuclei in smears stained by the May-Grünwald-Giemsa technique. The principle of this approach consists of eliminating, with the help of subtraction between two image lowpass filters, the small grey level differences among pixels, so that only high CG values are retained on the digitized image. The sum of these distinctive microareas is then taken as a fraction of the area of the peripherally eroded nucleus, and this ratio is designated as contrast gradient index (CGI) per nucleus. This method was tested on fine needle aspirates from 11 patients with benign breast disease (BBD) and 14 with mammary carcinoma (CA). For each specimen, 60 nuclei were analyzed, with a measuring time per nucleus of about 1 min. A high significant distinction between epithelial cell populations in BBD and CA, respectively, was obtained by variance analysis of all CGIs per nucleus (p = 2 x 10(-18). The median and the mean values of CGI per specimen were the next best discriminators, followed by the modes and the standard deviation of CGI per specimen. The percentage of nuclei per specimen with CGI values of greater than 12 was also significantly greater in CA than in BBD.

Adolescent

Diffuse centrocytic and/or centroblastic malignant non-Hodgkin's lymphomas: comparison of mitotic and pyknotic (apoptotic) indices.

Mitotic indices (MIs) and pyknotic (apoptotic) indices (PIs) were assessed in diffuse centrocytic (CC, n = 10), centroblastic/centrocytic (CB/CC, n = 18) and centroblastic (CB, n = 20) malignant non-Hodgkin's lymphomas (NHL). Significant differences were observed. MIs were lowest in CC (median: 0.07%), intermediate in CB/CC (0.18%) and highest in CB (0.43%) NHLs. The PIs exhibited a similar pattern. The PIs of CC (0.11%) and CB/CC (0.17%) NHLs were significantly different from those of CB lymphoma (0.62%). The ratios MI/PI per case, as well as MIs and PIs per case, varied greatly and showed considerable overlapping, thus documenting a marked inter-case and inter-group heterogeneity. MIs tended to loosely correlate with PIs in a non-linear fashion, which raises the question of feedback mechanisms. More information is needed on mitotic time (TM) and apoptotic time (TA), in order to estimate cell doubling time from data on MIs and PIs.

Adult

Distinct chemokinetic and chemotactic responses in neutrophil granulocytes.

Evidence has been presented to show that chemokinesis and chemotaxis of human neutrophil granulocytes can be controlled by distinct cellular mechanisms and by different chemicals. Materials such as human serum albumin or fibrinogen had chemokinetic but no chemotactic properties. Highly purified preparations of serum-derived peptides containing classical anaphylatoxin had detectable chemotactic activity only. Chemokinetic as well as chemotactic substances were required for the expression of chemotaxis in the form of efficient directional locomotion. The roles of chemokinesis and chemotaxis in the regulation of directional locomotion have been analyzed. Further experiments showed that the chemotactic response conforms to the law of Weber-Fechner. The number of cells which had accumulated in response to a chemotactic simulus was proportional to the logarithm of the concentration of the chemical substance. Readaptation from high to low chemotactic stimulus occurred only to a limited extent.

Chemotaxis, Leukocyte

Early appearance and mitotic activity of multinucleated giant cells in mice after combined injection of talc and prednisolone acetate. A model for studying rapid histiocytic polykarion formation in vivo.

Combined intraperitoneal injection of talc and particulate prednisolone acetate resulted in the formation of significant numbers of multinucleated giant cells within 48 hours. Neither one of these two agents had a comparable effect when injected alone. Evidence is presented showing that the multinucleated giant cells arose by cell fusion. Synchronous nuclear division could be observed in a considerable proportion of newly formed polykarions. Although the late prophases were usually normal, high proportions of abnormal mitotic figures were observed at later stages of mitosis, particularly in anaphase and telophase. The chromosome abnormalities were so severe that it is highly improbable that mitosis led to successful nuclear multiplication within a given syncytium. Similar to prednisolone acetate, prednisone elicited the formation of multinucleated giant cells when injected with talc. No polykarion formation was observed, however, when prednisolone acetate was substituted for other steroid preparations of similar particle size such as cortexon acetate, cortisone, or testosterone isobutyrate.

Animals

The chemokinetic effect of serum albumin.

Experiments performed by means of time lapse cinematography or the filter technique show that human serum albumin has marked chemokinetic effects on neutrophil cultured in Gey's solution. The average speed of the cells, as well as the proportion of neutrophils showing locomotion, is increased. Enhanced locomotion correlates with decreased attachment to the substratum as determined by morphological and functional criteria.

Adhesiveness

Relation between stimulus intensity and neutrophil chemotactic response.

The effect of chemotactic peptides which lack chemokinetic activity has been investigated. The neutrophil response is proportional to the logarithm of the stimulus intensity, or alternatively a power function with an exponent of 0.3. Equal responses are obtained for equal ratios between the peptide concentration in the lower compartment and the threshold concentration. The significance of Weber-Fechner's law in leucocyte chemotaxis is discussed.

Anaphylatoxins

Lymphopenia and lymph node histology following repetitive extracorporeal irradiation of blood in normal and thymectomized calves.

Repetitive extracorporeal irradiation of the circulating blood (RECIB) in normal or thymectomized calves and RECIB plus Imuran were used for comparative studies on the depletion of blood and lymph node lymphocytes. Elimination of the easily mobilizable pool of lymphocytes was almost complete within approximately 6 days after commencing RECIB and was reflected by a reduction of approximately 50% in the numbers of paracortical lymphocytes. Blood lymphocyte counts were reduced to approximately 1/3 to 1/4 of the pre-irradiation values. Thymectomized calves had lower pre-irradiation blood lymphocyte counts than non-operated controls, however, the reduction in the number of blood lymphocytes was proportionally similar. Continuation of RECIB beyond one week did not result in a further depletion of blood lymphocytes. The lymphocyte counts in the follicular cortex and in the medulla of lymph nodes were not significantly changed by the various procedures. RECIB of 8-16 days duration did not alter the number of germinal centers in non-thymectomized calves, however, in thymectomized animals treated with Recib, the number of germinal centers was reduced.

Animals

Significance of Hageman factor (coagulation factor XII) for neutrophil locomotion and chemotaxis.

Neutrophils separated from Hageman factor-deficient blood exhibit normal random and directional locomotion. No defect in cytotaxin formation could be demonstrated in Hageman factor-deficient plasma, nor did kallikrein inhibitor interfere with the chemotactic activity of normal immune complex-activated human plasma. The results suggest that the chemotactic activity which is detectable in unfractionated human plasma is not derived from Hageman factor-dependent pathways.

Antigen-Antibody Complex

Fate of thymocytes: studies with 125I-iododeoxyuridine and 3H-thymidine in mice.

Cortical thymocytes of young adult mice were labeled in situ with radioactive DNA precursors. As a result of cell emigration and cell death, total thymic radioactivity decreased within 8 days to 10% or less of that present on day 1. Accumulation of thymic migrants in peripheral lymphoid organs was estimated by computing the net thymus-derived radioactivity in these tissues. Thymic cell death was assessed by comparing values obtained with 125I-UdR to those acquired with 3H-TdR; The results indicate that cortical thymocytes migrate to the spleen, mesenteric lymph node, femurs and intestine; nevertheless, only a small fraction of the activity originally present in the thymus was recovered in these organs; the vast majority of newly formed cortical thymocytes apparently die after a relatively short life span. Exclusive of the fraction which dies in situ, evidence for thymocyte death is seen in bone marrow; however, most migrants appear to terminate in the intestine.

Animals

[Functional lymph node diagnosis].

This short review focuses on recent developments in the field of functional morphology of peripheral lymphoid tissues, in particular of lymph nodes. Emphasis is given to cellular and histological characteristics of lymph nodes in the course of cell-mediated and humoral immune responses. Against the background of regional and age-related changes, selected examples of a functional interpretation of structural changes are presented.

Humans