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Biomedical subjects

H Cottier

Publications and source records attributed to H Cottier.

At least 55 records · Page 3Linked to original sources
PubMed1987

Satisfactory primary tetanus antitoxin responses but markedly reduced germinal centre formation in first draining lymph nodes of ageing mice.

The present report deals with primary antibody responses to tetanus toxoid in 50-54-week-old ('ageing') as compared to 8-9-week-old ('young adult') mice. Antitoxin in the serum appeared 6 days earlier in the older than in the young animals, but in the latter reached 5 times higher titres on day 20. The magnitude of the proliferative response in the paracortex and the medulla of popliteal lymph nodes, as estimated by combined 3H-thymidine autoradiography and planimetry, was 3-7 times greater in the younger than in the older age group, thus approximately reflecting the difference in antibody titres on day 20. In contrast, germinal centre formation in response to the stimulus proved to be about 14 times less in ageing than in young adult mice. The findings demonstrate that, in the model system used, the age-related slopes of decline in humoral antibody responsiveness and proliferative reactivity in paracortex and medulla of first regional lymph nodes tend to be in parallel, while the ability of the immune apparatus to form germinal centres at this site deteriorates at a considerably faster pace. Results are also in line with the notion that centroblasts/centrocytes contribute little, if anything, to the ongoing antibody production elicited by the same stimulus which had triggered germinal centre formation. Finally, the observations made disprove the general validity of the suggestion that immune reactivity is maintained on the same level throughout life if tested with a novel antigen.

Aging↗
PubMed1986

Immunodeficiency and cancer: mechanisms involved.

This is a short overview concerning possible relationships between immunodeficiency and cancerogenesis/leukemogenesis. Following introductory remarks on concomitant and sinecomitant antitumor immunity, various factors/mechanisms that could influence tumor-host-interactions are discussed, in particular properties of neoplastic cell lines, the microenvironment, cellular components of nonspecific resistance, and specific, i.e. antigen-directed, cell-mediated and humoral immune responses against cancer cells. The increased incidence of malignant neoplastic processes in patients with inherited or acquired immunodeficiency raises the question if a lack of antitumoral defense or ineffective antiviral immunity is more important. Available data indicate that once a cancer has reached a certain size, the chances for the host to reject it solely with the help of its immune apparatus are minimal. The possibility remains that immune reactions may be more efficacious against small numbers of immunogenic tumor cells, i.e. in the very earliest phase of a neoplastic process and when the cancer begins to metastasize.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Stimulation of proliferation of murine lymphocytes by the calcium ionophore A 23187 in the absence of serum: the requirement for thiols.

The proliferation of mouse spleen cells and T-lymphocytes, initiated by the calcium ionophore A 23187 was studied by a serum-free culture technique. In contrast to Con A, A 23187 was capable of stimulating cells only if 2-mercaptoethanol, cysteine and glutathione (reduced form), respectively, were present in the culture medium. In the absence of one of these compounds a stimulating activity of A 23187 was observed only with high concentrations of cells (i.e., 10(7)/ml). With glutathione present, the cells could be stimulated only at concentrations of A 23187 which were found to be suboptimal in cultures with 2-mercaptoethanol. Human serum, fetal calf serum and bovine serum albumin shifted the active and optimally stimulating concentrations of A 23187 to higher values. A similar effect was observed with sera- and Con A-treated cells. The effect of sera and albumin was paralleled by a protecting effect of cells against high concentrations of A 23187.

Animals↗
PubMed1986

Immunoglobulin in chronic inflammatory diseases.

Several case studies are presented to illustrate the success of intravenous gammaglobulin (IVIG) therapy in ulcerative colitis, Crohn's disease, chronic anterior uveitis, herpes zoster, and relapsing genital herpes simplex. Hypothetical mechanisms explain the marked improvement of the chronic disorders, with particular emphasis on substitution of specific antibodies. The recently recognized heterogeneity of the major histocompatibility complex (MHC) is explored as one possible explanation for low and high responders to particular antigens. It is suggested that various chronic inflammatory disorders result from ineffective immune responses, and that the administration of IVIG may shift the delicate balance between the pathogen and the host to favor the latter.

Adult↗
PubMed1986

Qualitative and quantitative assessment of human polymorphonuclear leukocyte (PMNL) functions.

The current status on human PMNL separation, storage conditions, and quantitative assessment of cell functions is discussed. Human peripheral blood PMNLs are multifunctional cells which may be activated by several soluble and particulate stimuli. A variety of methods for the isolation of PMNLs and testing of cell functions is described which may be used in the clinical and the research laboratory. Detailed information on the quantitative assessment of PMNL motility, phagocytosis, microbial killing, exocytosis, and oxygen metabolite generation is given. Recently developed biochemical and immunological methods which may be employed for detection of structural and metabolic changes in normal and pathological PMNLs are also included.

Blood Bactericidal Activity↗
PubMed1986

Morphometric distinction of granulomas in tuberculosis and sarcoidosis. Difference in nuclear profiles.

Morphometric measurements were carried out on epithelioid-cell nuclei of noncaseating granulomas in paraffin-embedded sections of lymph node biopsy specimens originating from 15 patients with sarcoidosis and from 18 patients with tuberculosis. The results, which were obtained with the help of a computer-assisted tracing device, established highly significant differences in shape and size of epithelioid-cell nuclear profiles in these two diseases. Direct measurements and computations on these results showed that epithelioid-cell nuclear profiles in sarcoidosis have a smaller mean and median perimeter (boundary length), area and long diameter (maximum length of the nuclear profile) and exhibit a more plump, elliptical-like shape than do those in tuberculous granulomas. Epithelioid-cell nuclear profiles of the latter, as a whole, show more irregular contours, resembling those, e.g., of the sole of a shoe or other elongated patterns. Differences in shape of nuclear profiles were best demonstrated by a size-independent form factor (4 pi *area/perimeter2).

Adolescent↗
PubMed1985

Phorbol myristate acetate (PMA) suppresses polarization and locomotion and alters F-actin content of Walker carcinosarcoma cells.

This study demonstrates a novel feature of PMA, its ability to suppress chemokinetic polarization and locomotion of tumor cells. Walker carcinosarcoma cells exhibit two distinct types of polarization and locomotion, i.e. spontaneous polarization characterized by ruffles at the front and stimulated polarization and locomotion in response to the microtubule-disassembling agents colchicine, vinblastine and nocodazole, which are characterized by blebbing at the front. The tumor promotor phorbol myristate acetate (PMA), but not phorbol, was found to suppress both types of polarization and random locomotion at concentrations between 10(-8) and 10(-6)M. The effect of 10(-6)M PMA was virtually complete within 5 min. Inhibition of locomotion was due to both a reduction in the speed of migrating cells and the proportion of migrating cells. Changes in shape and chemokinesis of Walker carcinosarcoma cells were associated with alterations in the relative amount and the topographical distribution of F-actin as determined by NBD-phallacidin binding. Suppression by PMA was associated with loss of the polar topographical distribution of F-actin visualized by NBD-phallacidin binding. In the presence of PMA, the relative amount of F-actin was higher than in unstimulated controls and lower in cells exposed to microtubule-disassembling agents.

Actin Cytoskeleton↗
PubMed1985

Morphological and biochemical responses of leukocytes in chemokinesis and chemotaxis.

Morphological changes associated with leukocyte chemokinesis and chemotaxis are briefly described. Leukocyte stimulation by chemokinetic and chemotactic factors (cytotaxins) elicits various biochemical responses including ligand-receptor interactions, ion fluxes, alterations in phospholipid and arachidonic acid metabolism, cyclic nucleotides, protein phosphorylation and reorganization of the cytoskeleton. These biochemical processes may be related to signal transduction, the effector mechanisms of directional locomotion or possibly other leukocyte responses which occur in parallel.

Animals↗
PubMed1985

Thymic lymphopoiesis: protected from, or influenced by, external stimulation?

The mechanisms regulating thymic lymphopoiesis are still a matter of debate. Intracortical proliferation and differentiation of thymocytes are thought to be controlled by locally produced humoral factors and close contact with epithelial, possibly also phagocytic, cells, and restricted by products of the major histocompatibility complex. The observation of a translocation of intraabdominally introduced PVP-coated silica particles (Percoll) via parathymic lymph vessels and through the thymic capsule into the cortical parenchyma demonstrates that the thymic cortex is accessible to materials carried with the transcapsular flux of interstitial fluid, and that this barrier is less effective than the blood-thymus barrier. The proliferative activity of cortical thymocytes following an intraabdominal injection of particulate tetanus toxoid was compared in sites adjacent to, and distant from, parathymic lymph nodes. Absolute numbers of DNA-synthesizing thymocytes were found to be much higher in cortical areas close to the lymph nodes, where lymphatic vessels are most numerous, than on the opposite sides of the thymic lobes. Taken together, these findings indicate that--in addition to intrinsic control mechanisms--cortical thymocyte production may be influenced by peripheral stimulation to some extent, and that materials from sites which are drained by parathymic lymph nodes may be important in this respect.

Animals↗
PubMed1984

Proliferative patterns of lymphocytes in lymph nodes during tumour development: involvement of T and B cell areas.

DNA-synthetizing lymphocytes were identified in the lymph nodes regional and more distal to the site of developing P-815 tumours by incorporation of [3H]-thymidine followed by autoradiography of lymph node sections. It appeared that not only T but also B cell areas of draining and to a lesser extent of distal lymph nodes were stimulated by the growing tumour. This result was unexpected since neither humoral nor tumour cell-bound antibody could be identified so far as a functional correlate of B cell stimulation. In general the proliferative response of lymphocytes followed a biphasic pattern with an early peak of reactivity on days 2-3 and a second peak around day 12-15 after tumour cell inoculation. In the draining (axillary) lymph node the second peak of reactivity was suppressed, possibly as a consequence of metastatic tumour cells in this node when tumour cells were inoculated in the flank. The pattern of lymphocyte stimulation revealed larger individual variations after tumour cell inoculation in the flank than the foot pad. These results were associated with a slower and less regular drainage of carbon particles from the flank to the axillary and exceptionally the brachial lymph node than from the foot pad to the popliteal node after injection of India ink.

Animals↗
PubMed1984

Comparison of locomotion, chemotaxis and adhesiveness of rabbit neutrophils from blood and peritoneal exudates.

We compared the spontaneous behaviour (motility, adhesiveness, locomotion) and the chemotactic responses of exudate and blood-borne neutrophils. Directional locomotion of exudate neutrophils in 2% HSA-Gey's towards exudate fluid was not significantly changed, the response to activated autologous plasma diminished, and that to f-Met-Leu-Phe (10(-9) M) increased in comparison with blood-borne cells. The spontaneous behaviour of exudate cells in 2% HSA-Gey's (no gradient) differed markedly from that of blood-borne cells. In tissue culture medium (2% HSA-Gey's) exudate cells showed heightened motility in suspension and greater adhesiveness to glass substrata. These differences were eliminated by culturing the cells in their physiological media (i.e. plasma or exudate fluid). In contrast to blood-borne cells, exudate neutrophils tended to aggregate spontaneously. There was no correlation between neutrophil aggregation and adhesion to glass substrata of exudate cells in exudate fluid.

Animals↗
PubMed1983

The mechanism of SiO2 (Aerosil)-mediated enhancement of the proliferative response of mouse spleen lymphocytes to antigen and mitogens in a serum-free system.

SiO2 particles enhanced the in vitro proliferation of splenic B cells obtained from BALB/c mice immunized with sheep erythrocytes. T cells from immunized animals were capable of replacing SiO2 with regard to the enhancement of both in vitro proliferation and the primary immune response. In addition, the stimulating effect of IgG, phytohemagglutinin (PHA) and concanavalin A (Con A) on spleen lymphocytes was also augmented by SiO2. The enhancing effect of SiO2 was higher at suboptimal than at supraoptimal concentrations of Con A. SiO2 is capable of binding Con A. The SiO2-bound lectin retained its mitogenic effect on spleen cells and, under certain conditions, SiO2-bound Con A was considerably more active in this respect than the free substance.

Animals↗
PubMed1983

Regional differences in renewal rates of fibroblasts in young adult female mice.

Young adult female mice were given a total of 90 intraperitoneal injections each of (methyl-3H)thymidine (3HTdR) at intervals of 8 h over 30 days to establish renewal rates of fibroblasts in various locations. Radioautographs prepared from punch biopsy material of the ears, taken repeatedly during the labeling procedure, revealed an approximately linear increase of labeling indices of dermal fibroblasts with time. Labeling indices of fibroblasts at the end of repetitive injections of 3HTdR differed depending on the site and/or type of connective tissues examined. Low values were obtained for fibroblasts in the leptomeninx (3.9%), the tracheal wall (4.4%), the achilles tendon (5.8%) and the dermis of the ear (6.5%), while higher values were registered for fibroblasts located in the lower half of the abdominal dermis (12.3%), peritendinous sheaths (12.6%), the interstitial connective tissue of the thigh muscles (12.9%), the submucosa of the colon (23%), the fibrous capsule of the adrenals (25.7%), and the upper half of the abdominal dermis (26%). These regional differences, with the exception of the skin and possibly of the tracheal wall, did not correlate with local temperature. Possible additional factors influencing fibroblast renewal rates may include the type of connective tissue, the degree of vascularization, mechanical stress and hormonal action. Estimated turnover times, based on the assumptions of a DNA synthesis time of 6 h or more and a linear increase of labeling indices as a function of time of repetitive labeling, range from about 90 to more than 700 days. The higher values approximate the median life span of the mouse strain used.

Adrenal Glands↗
PubMed1983

Early changes in lymphocyte traffic between distant lymph nodes following regional antigenic stimulation.

Regional labeling of mice by injection of cytidine-3H ([3H]CR) into the footpad of the left hind leg was used to evaluate lymphocyte traffic from the left regional nodes to the right popliteal lymph node (PLN) within a 24-h period, with or without concomitant primary or secondary stimulation of the right PLN with fluid tetanus toxoid. Results indicate that 1) in the case of primary antigen injection the relative contribution of lymphocytes from the left regional nodes to the small lymphocyte population present in the stimulated right PLN 24 h after labeling was slightly, but not significantly, greater than in non-stimulated controls; 2) a booster injection of antigen into the right hind leg footpad resulted in a significantly smaller relative contribution of lymphocytes from the previously primed left regional nodes to the small lymphocyte population in the right PLN, 24 h after injection of [3H]CR and secondary stimulation, as compared with controls or animals given a primary stimulation to the receiver node; and 3) in contrast to controls and mice subjected to primary stimulation only, the right PLN 24 h after booster contained a significant number of large lymphoid cells which, or whose precursors, had migrated to this site from contralateral nodes within a day, possibly also in the form of small lymphocytes. These findings are discussed in relation to the problem of lymphocyte recruitment and divergent behavior of non-committed lymphocytes as compared with memory cells in the initial phase after primary or secondary antigenic stimulation.

Animals↗
PubMed1983

Crawling-like movements, adhesion to solid substrata and chemokinesis of neutrophil granulocytes.

We analysed the chemokinetic actions of fMet-Leu-Phe (FMLP) and human serum albumin (HSA) on preparations of human neutrophils. Our work focused on the extent to which these agents, individually or in combination, affected locomotion by inducing changes in motile activity and/or the degree of cellular adhesion to the substratum. Because polymorphonuclear leucocyte (PMN) preparations derived from different individuals were found to exhibit broad variations in their basal motility and level of adhesiveness to glass substrata, it became of major interest to clarify mechanisms responsible for the reported variations in neutrophil responses to FMLP. We performed detailed studies on three separate PMN preparations, which differed in terms of their basal motility and adhesiveness. The unequivocal findings that emerged from this study were as follows: (1) HSA did not stimulate or modify motility of cells in suspension. Its orthokinetic effect was exclusively due to its capacity to decrease adhesion to the substratum. It prevented immobilization of motile cells that made contact with the substratum. (2) The orthokinetic effect of FMLP was primarily due to its effects on motility, but there were also secondary effects on spreading and adhesion. The peak chemokinetic activity of FMLP occurred at 10(-8)M, when measured by the two-filter count method and this was correlated with the percentage of polarized neutrophils in suspension. (3) The response to HSA and/or FMLP depended on the basal activity of the cells. If the cells were non-motile and spherical, HSA had no chemokinetic effect. Such an effect was only observed with cells that were initially motile. In contrast, the stimulatory effect of FMLP on motility and locomotion was marked in cases where basal motile activity of the neutrophils was low. If the basal motile activity was high, motility and locomotion could not be stimulated further. Therefore, the chemokinetic effects of HSA and FMLP can be predicted when one knows the basal motile activity of the neutrophils. The variable effect of FMLP on adhesion may also contribute to the regulation of locomotion. These findings help to explain earlier conflicting reports on the chemokinetic effect of FMLP. (4) FMLP can elicit simultaneous changes in motility and adhesiveness, which may have synergistic or antagonistic effects on locomotion. (5) The average speed of the whole neutrophil population is essentially regulated by changes in the proportion of locomoting cells and not, or to a lesser extent, by changes in the speed of the locomoting subset.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion↗