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Biomedical subjects

C Thierry

Publications and source records attributed to C Thierry.

At least 19 recordsLinked to original sources

Influence of the mode of load carriage on the static posture of the pelvic girdle and the thoracic and lumbar spine in vivo.

The influence of various modes of carrying a load of 16 kg (15.69 DaN) on the static positioning of the pelvic girdle and the thoracic and lumbar segments of the spine was examined in seven male subjects. The displacement of cutaneous markers attached to easily palpable skeletal landmarks was recorded using 4 CCD cameras; the data acquired were analysed using an optoelectronic technique (SAGA3). The subjects stood upright on an AMTI biomechanical force platform, from which the ground reaction forces enabled displacements of the centre of gravity axis and thus the moment of the mass carried to be determined. The modes of load carriage examined were: 1) in a case in the left hand; 2) in a case in the right hand; 3) equally in two cases; 4) on the head; 5) in a rucksack; and 6) in an anterior bag. The results showed displacements of the pelvic girdle, the caudal and cranial lumbar segments, and the caudal and cranial thoracic segments in the three orthogonal planes (sagittal, frontal and transverse). The influence of the moment created by the load was seen in the statokinesigrams. The use of external markers using an optoelectronic technique, in association with the ground reaction forces, enables the mode of load carriage to be determined. The results show that the influence of the moment exerted by the mode of load carriage on the gravity axis has important ergonomic consequences.

Adult↗

Quantification of ERBB2 protein expression in breast cancer: three levels of expression defined by their clinico-pathological correlations.

Activation of the ERBB2 oncogene seems to be an early event in breast cancer progression and prevalent in in situ carcinomas. However, its prognosis value, albeit recognized for node-positive patients, remains controversial for those without apparent nodal involvement. One possible reason for this problem is likely to be the difficulty of defining threshold levels for ERBB2 protein overexpression. ERBB2 protein expression was therefore analyzed in primary invasive breast tumors. Quantification of the gene product by a commercial ELISA test was compared to results obtained by immunohistochemistry and western blotting, as well as to gene amplification status determined by Southern blotting. Correlations between results obtained by the different techniques were highly significant (P value < 10(-6)). Nevertheless, ELISA permitted us to determine three levels of protein expression corresponding to distinct tumor subsets. 1) Tumors with p185/ERBB2 expression levels exceeding 10 U/microgram exhibited in most cases amplification of the gene (83% of cases), DNA aneuploidy (81%) and absence of estrogen receptor (ER) (44%). Such high levels of protein expression were exclusively observed in invasive ductal carcinomas and were prevalent in those showing a significant in situ component. 2) "Intermediate" levels of expression (3-10 U/micrograms) were rarely observed in tumors exhibiting gene amplification (9%), but were preferentially found in cancers of more favorable prognosis (only 49% were aneuploid and 9% estrogen receptor negative). 3) Levels of p185/ERBB2 below 3 U/micrograms were detected in benign mastopathies and, thus, carcinomas presenting such levels were scored ERBB2 negative. Interestingly, invasive lobular carcinomas were rarely ERBB2 positive, and if so, only at intermediate levels. Moreover, our data show a complex interrelationship between p185/ERBB2 expression and ER levels. Indeed, tumors with more than 10 U/micrograms of p185 were prevalently ER, whereas those with p185 ranging from 3 to 10 U presented elevated levels of ER.

Aneuploidy↗

Solubilization of a human lymphocyte factor for autorosette.

With incubation at 45 degrees C, human peripheral blood lymphocytes (PBL) loose 80% of their capacity to form 1-hr autorosettes (AR). However, the addition of supernatant from heated lymphocytes (SHL) restores 93% of their rosette-forming capacity, while producing an inhibitory effect on nonincubated lymphocytes. A soluble factor present in SHL is active to a 1/5000 dilution; is absorbable on autologous red blood cells but not on sheep red blood cells; is RNase and DNase resistant and sensitive to trypsin and pronase; and acts variably on allogenic cells.

Animals↗

Human autologous rosettes. IV. Their relation with interleukin 2 activity production and natural killer cells in cancer patients.

Peripheral blood lymphocytes (PBL) of solid-tumor-bearing cancer patients produced a lower interleukin 2 (IL-2) activity after lectin stimulation than did those from normal subjects. Moreover natural killer (NK) cell activity and autologous rosette forming (ARF) cell rate are found significantly correlated with IL-2 production in these patients. No direct relation is observed between ARF cell ratio and NK cell activity in a given patient. A central role for IL-2 in cancer patient immune dysfunctions is suggested. Two lines of pathogenetic mechanisms are documented. First, PBL exhibited cellular function defects, namely, autologous receptor expression, IL-2 production, and NK activity. Second, these dysfunctions involved, at least partly, plasma factors. The possibility of specific deficiency, (e.g., thymic factors) is not documented. Conversely it is demonstrated that patient plasma contain immunosuppressive factor(s) that block(s) IL-2 production and ARF cell expression. Involvement of ARF cell receptor in T-cell activation is discussed.

Adult↗

Diminished interleukin-2 activity production in cancer patients bearing solid tumors and its relationship with natural killer cells.

Interleukin-2 (IL-2) activity production by stimulated peripheral blood lymphocytes (PBL) from solid tumor bearing cancer patients was lower than in normal subjects. Natural-killer (NK) cell activity in the PBL of cancer patients was very significantly correlated to IL-2 activity production (P less than 0.001). These results might suggest a central role for IL-2 in the immune dysfunctions in cancer patients, and the possible use of IL-2 as an immunological response modifier in these patients.

Adult↗

Modulation of human T lymphocyte functions by isoprinosine.

Isoprinosine was shown to alter certain T cell functions. In vitro, it has previously been shown to induce suppressor cell activity in both mouse and human lymphocytes. Our in vitro results suggest that Isoprinosine acts on immune balance by increasing the number of non-suppressor T cells and, at least partially blocks Con A induced suppressor activity. In vitro NK activity remained unaltered.

Adjuvants, Immunologic↗

Amplification of the polyclonal activation of human T cells. I. Null-cell products promote the polyclonal proliferation of T cells.

Synergy can be observed in the proliferative response to mitogens of cultures containing human T and Null cells when compared with those containing only highly purified cells of those two types. This synergy was analysed (i) by evaluation of the proliferative response at each step of the purification process leading to separation of T and Null cells; (ii) by back-mixing T and Nul cells at different rations; and (iii) by evaluation of the proliferative response of free suspension cultures of T cells overlaying a semi-solid layer containing Null cells, or of free suspension cultures of Null cells over a semi-solid culture layer of T cells. The following conclusions were reached: (i) purified Null cells are unresponsive to mitogen when cultured alone or in the presence of diffusible T-cell products; (ii) the T cells are less responsive when cultured alone than in the presence of Null cells or diffusible Null cell products. Thus the synergistic effect observed between T and Null cells is not due to the promotion of Null-cell proliferation by T -cell products but can be accounted for by diffusible Null-cell products enhancing the process of T lymphocyte activation by mitogens.

Adult↗

Slower step of the polycyclic aromatic hydrocarbons metabolism: kinetic data from microspectrofluorometric techniques.

A microspectrofluorometer has been used for kinetic studies of the decrease of benzo(a)pyrene and benzo(k)fluoranthene fluorescence. This decrease is observed for single living cells: L cells and human peripheral blood monocytes, after their incubation which culture medium containing these compounds and washing the petri dish with fresh medium. The entire fluorescence spectra is recorded at given time intervals in order to watch at some eventual spectral modification. The fluorescence decrease is monoexponential and its parameters are computed with a program based on the least squares fit method. Such determination shows no difference between the calculated rate constants of metabolisation for B(a)P and B(k)F and, as long as we consider L cells with a similar morphological shape, only statistical fluctuations of the rate constants of metabolism are observed. As compared, monocytes show faster kinetics of the decrease of the B(a)P intracellular fluorescence due to B(a)P metabolism, and also a more reached dispersion of the values of the rate constant than the one observed for L cells indicating some heterogeneity in the monocyte population of each donor.

Aryl Hydrocarbon Hydroxylases↗

[Modulation of suppressor activity by thymosin].

Modulation of suppressor cell activity by thymosin was evaluated in vivo in a murine tumor system, and in vitro on human lymphocytes. We showed that splenocytes from tumor bearing mice were able to enhance tumor growth in a syngeneic system. This enhancement was T dependent and disappeared by Thymosin treatment. A decrease of Tumor size associated with injection of bone marrow cells treated by thymosin was observed. In the human system we showed that ConA stimulated lymphocytes were able to suppress the response of normal lymphocytes to PHA, PWM and ConA, and in MLC. This effect was significantly blocked in presence of thymosin fraction 5.

Animals↗

Human T lymphocyte colonies. I. Surface markers and cytotoxic potential of colony cells.

Colonies were obtained from peripheral blood lymphocytes (PBL) grown in soft agar in the presence of PHAM or PHAp mitogens. One out of 130 PBL was able to generate a colony. Colony cells were mass harvested and assayed for surface markers and cytotoxic potential. Most of the colony cells (83%) form spontaneous rosettes with sheep-red blood cells (RBC) and bear the human T lymphocyte antigens (HTLA) (92%). A significant amount of colony cells able to bind autologous RBC was detected (24%). The capacity of PBL and colony cells to bind Ox-RBC sensitized with rabbit anti-Ox-RBC IgM (EAM complexes) was measured: only 15% of colony cells compared to 49% of the PBL formed EAM rosettes. The capacity of cells to bind the Fc portion of antigen-complexed IgG was investigated by two rosette assays: using Chicken or Ox-RBC sensitized with a rabbit anti-Chicken-RBC or Ox-RBC IgG (Chicken EAG or Ox-EAG complexes). The percentage of colony cells forming Chicken EAG rosettes was low (3.6%) compared to PBL (12%). This percentage was significantly increased with PHAp, and not PHAM stimulation (11%). Using Ox-EAG complexes, we confirmed the low percentage of EAG rosettes in colony cells under PHAM stimulation (4.7%) compared to PBL (21%). A significant cytotoxic capacity (spontaneous or antibody dependent) was found in colony cells after PHAM stimulation. This method of culture is able to generate clones of T cells and conserve T cell subsets and cytotoxic potential usually found in a T purified population. In further studies, it will be interesting to investigate if each clone possesses specific markers and cytotoxic potential and is able to maintain this differentiation step in long term culture.

Antigen-Antibody Complex↗

Human T-lymphocyte colonies: generation of colonies in different lymphocyte subpopulations.

The generation of human T-lymphocyte colonies from different lymphocyte subpopulations in the presence of PHA alone, or PHA plus media conditioned by PHA-stimulated lymphocytes (PHA-LCM) has been investigated. The separation technique consisted of phagocytic cell depletion by carbonyl iron treatment and fractionation of non-phagocytic cells (NP cells) into B cells and T + null cells by affinity chromatography on an anti-F(ab')2 column. The T cells were separated from the null cells by E-rosette sedimentation. Under these conditions, we showed that: no T-lymphocyte colonies were obtained from the null-cell subset in the presence of PHA of PHA + PHA-LCM; T-lymphocyte-colony formation potential was retained in the T-cell subset. Some variability was observed in the production of T colonies using peripheral blood lymphocytes (PBL) from different donors. Low producers and high producers of T-lymphocyte colonies were encountered. The low production of T-lymphocyte colonies observed in some donors was due to a suppressive effect mediated by the phagocytic cells, probably monocytes. The anti-F(ab')2 immunoadsorbent retained a cell population necessary for T-lymphocyte colony growth.

Adult↗

Ability of thymosin to decrease in vivo and in vitro suppressor cell activity in tumor bearing mice and cancer patients.

We have demonstrated that splenic lymphocytes from normal syngeneic animals can stimulate tumor growth. This effect is T-cell dependent. Preincubation of these lymphocytes with thymosin not only blocks facilitated tumor growth but can induce a significant reduction of local tumor growth and number of pulmonary metastases. Furthermore, thymosin can also block the expression of suppressor activity of lymphocytes either stimulated by Con A or originating from various advanced solid tumor bearing patients. These results therefore suggest that thymosin is able to modulate, directly or indirectly, functional expression of suppressor cells.

Animals↗

Immune imbalance in cancer patients.

The immune status of the tumor-bearing patient remains poorly defined. In various solid-tumor-bearing patients, we demonstrated the absence of ADCC modifications in the patient in relapse or in evolution. These same patients presented a significant increase in immune complexes when compared with patients in remission. Furthermore, we noted a decreased NK activity, a decreased number of ARFC, corresponding to a helper T cell subpopulation, and a corollary increase in T-dependent suppressor activity. These results, on the whole, suggest an immune imbalance and that the helper cell-suppressor cell ratio should be investigated in greater depth within the context of the immune response in the cancer patient.

Antibody-Dependent Cell Cytotoxicity↗

Electrophoretic mobility of peripheral non-B human Fc gamma-receptors bearing lymphocytes.

The electrophoretic mobilities of separated "null" lymphocytes and of null and T cells bearing receptors for the fragment of immunoglobulins (Fc) portion of IgG have been studied in normal human blood. The data have been compared with those of other circulating subsets and with more conventional marker techniques. A large proportion of B cells was removed by nylon wool adherence. Further purification of the effluent cells separated 3 non-B populations using the property of sheep's red blood cells to form 2 types of rosettes with T cells on the basis of their relative affinity: "active" rosettes, and low affinity E-rosettes. A population of "null" cells was obtained which was effluent of the nylon wool column and non rosette-forming cells with SRBC (E-RFC). The average purity of this population was 85%; it was found to contain an increased proportion of rosette-forming cells with IgG coated erythrocytes (EA-IgG RFC) (41.3 +/- 10.4% vs. 11.9 +/- 3.8% in the total population) and exhibited high spontaneous incorporation of thymidine but low response to mitogens. The "null" cell population and its erythrocyte-antibody complex-rosette forming cells (EA-RFC) exhibited a defined electrophoretic mobility, centered between 1.05 and 1.15 micrometer. sec-1. v-1. cm in NaCl 0.145 M. The T populations, defined as ERFC, possessed different electrophoretic mobilities, and contained different proportions of Fc gamma receptor-bearing cells. Possessing an e. m. generally greater than 1.15 micrometer. sec-1. v-1. cm., high affinity "active" rosettes did not appear to contain EA-RFC, while the low affinity ERFC contained 18% (8 to 33) EA (IgG) RFC, and had an e.m. comprised between 1.00 and 1.15 micrometer. sec-1. v-1. cm. The presence of antibody-dependent cellular cytotoxicity was found to correlate with EA-RFC: mainly in EA-RFC of the "null" cells, but also to a lesser extent in EA-RFC of the low affinity ERFC. In normal human blood, these non-B Fc gamma receptor bearing cells appeared to possess a comparable electrophoretic mobility centered between 1.05 and 1.15 micrometer. sec-1. v-1. cm. in the "null" and low affinity ERFC subsets.

Adult↗

Human K cell activity. I. Relation to effector cells buoyant density.

In order to disclose a relation between human K cell activity and effector cells buoyant density, this activity was tested, against antibody sensitized 51Cr labelled L1210 cells, in lymphocytes subsets obtained by centrifugation to equilibrium in discontinuous bovine serum albumin gradients. Since K cell activity is mainly present in null and T cells, this study focused on the buoyant density subsets of human T and null cells. Our results show that, in these T and null cells, K cell activity is directly related to cell density, the less dense fraction having the highest cytotoxic capacity. From the recovery of Lytic Units, it is shown that the K cell pool can be associated with the population of activated or precursor cells in human peripheral blood.

Antibody-Dependent Cell Cytotoxicity↗