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Biomedical subjects

F Martin

Publications and source records attributed to F Martin.

At least 91 records · Page 5Linked to original sources
PubMed2000

Role of tumor cell apoptosis in tumor antigen migration to the draining lymph nodes.

Establishment of an immune response against cancer may depend on the capacity of dendritic cells to transfer tumor Ags into T cell-rich areas. To check this possibility, we used a colon cancer cell variant that yields tumors undergoing complete T cell-dependent rejection when injected into syngeneic rats. We previously demonstrated that immunogenicity of these tumors depended on the early apoptosis of a part of these tumor cells. In this paper we show that fluorescent tumor cell proteins are released from FITC-labeled tumor cells and undergo engulfment by tumor-infiltrating monocytes without a phenotype of mature dendritic cells or macrophages. Fluorescence-labeled mononuclear cells with a phenotype of MHC class II+ dendritic cells are also found in the T cell areas of the draining lymph nodes. Interestingly, no fluorescent cell can be found in lymph nodes after a s.c. injection of Bcl2-transfected apoptosis-resistant tumor cells that yielded progressive tumors. Proliferation of tumor-immune T lymphocytes was induced by dendritic cells isolated from the draining lymph nodes recovered after a s.c. injection of apoptosis-sensitive, but not apoptosis-resistant, tumor cells. These results show that tumor cell apoptosis releases proteins that are engulfed by inflammatory cells in the tumor, then transported to lymph node T cell areas where they can induce a specific immune response leading to tumor rejection.

Adenocarcinoma↗
PubMed2000

Transcription factor NF 1 expression in involuting mammary gland.

Transcripts of each of the four NF1 genes (NF1 A, B, C (CTF/NF1) and X) are expressed in both lactating and involuting mouse mammary gland but there is an indication that increased expression of an NF1 C (CTF/NF1) transcript accompanies early involution. The involution-associated 74 kD NF1 and the 114 kD lactation-associated NF1 are recognised by an anti-NF1 C-specific antibody that does not cross-react with other NF1 proteins. It is most likely that this lactation/involution switch in NF1 factors represents a change in expression of NF1 C (CTF/NF1) proteins.

Animals↗
PubMed2000

A systematic approach to optimum working conditions with inductively coupled plasma atomic emission spectrometry.

Optimum experimental factors were determined for the analytical determination of Al, Cd, Fe, Pb, and Zn by ICP atomic emission spectrometry. Based on systematically determined factor levels, working conditions were found that gave similar, and sometimes better results compared with the hitherto used levels of factors. All measurements were performed with a sampling time of 150 ms as often used in routine analysis in the laboratory. This optimization resulted in a reduced outer plasma gas flow from 15 L/min argon to 12 L/min without any relevant changes of the achievable detection limits. A serious problem was that only one analytical line of Al could be used. A comparison with the lower limit of application (comparable with the detection limit) from German directive DIN 38406, part 22 ([1]), showed that the detection limits of Al and Fe are superior, whereas for Cd there was only little improvement. The detection limits of Zn and especially Pb are always higher than the lower range of application under these conditions. Therefore, the use of two device-parameter sets for hard and soft lines, respectively, is strongly suggested. Maps with the observed signal-to-noise-ratios were systematically acquired for each element analyzed in connection with different strategies for optimum search. mon compromise condition (combined analysis) and the limits of quantification demanded in the German directive DIN 38406, part 22 [1]. Only four, but the most important, experimental factors were changed, the other experimental factors were always kept constant (Tables 1 and 2).

Journal Article↗
PubMed2000

Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk.

Using immunoglobulin heavy chain transgenic mice, we show that B cell clones reaching the long-lived pool are heterogeneous: some are enriched in the CD21(high) compartment (mostly marginal zone [MZ]), others reside primarily in the follicles (FO). Altering the composition of the B cell receptor through N region additions decreases the rate of clonal production and the MZ enrichment. This process can be recapitulated by purified CD21(low) B cells and is due to a preferential clonal survival that requires a functional btk tyrosine kinase. We also show that generation of the MZ population is dependent on CD19. These findings suggest that the MZ B cell repertoire is positively selected and have functional implications for antigenic responses effected by B cells from this microenvironment.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2000

In vivo selection of lethal mutations reveals two functional domains in arginyl-tRNA synthetase.

Using random mutagenesis and a genetic screening in yeast, we isolated 26 mutations that inactivate Saccharomyces cerevisiae arginyl-tRNA synthetase (ArgRS). The mutations were identified and the kinetic parameters of the corresponding proteins were tested after purification of the expression products in Escherichia coli. The effects were interpreted in the light of the crystal structure of ArgRS. Eighteen functional residues were found around the arginine-binding pocket and eight others in the carboxy-terminal domain of the enzyme. Mutations of these residues all act by strongly impairing the rates of tRNA charging and arginine activation. Thus, ArgRS and tRNA(Arg) can be considered as a kind of ribonucleoprotein, where the tRNA, before being charged, is acting as a cofactor that activates the enzyme. Furthermore, by using different tRNA(Arg) isoacceptors and heterologous tRNA(Asp), we highlighted the crucial role of several residues of the carboxy-terminal domain in tRNA recognition and discrimination.

Arginine-tRNA Ligase↗
PubMed2000

Laminin-rich extracellular matrix association with mammary epithelial cells suppresses Brca1 expression.

Brca1 mRNA was detectable in female mouse mammary gland tissue from adult virgins, during pregnancy and early lactation. It was associated with phases of mammary epithelial cell proliferation and differentiation but the pattern of Brca1 expression was dissociable from that of a true differentiation marker, beta-casein, by virtue of its significant expression in the virgin gland and termination of its expression in early lactation. In a primary cell culture model, association of a laminin-rich extracellular matrix (ECM) with mammary epithelial cells was required for cell survival and cell differentiation and suppressed Brca1 expression in these cells. ECM-association may significantly contribute to the final restriction in Brca1 expression in the lactating gland in vivo. Interestingly, our results suggest that mammary epithelial cells undergo apoptosis both when expressing and when not expressing Brca1, depending on whether the dying cell populations had been terminally differentiated or not.

Animals↗
PubMed2000

MAP kinase pathway signalling is essential for extracellular matrix determined mammary epithelial cell survival.

Mammary epithelial cells in primary cell culture require both growth factors and specific extracellular matrix (ECM)-attachment for survival. Here we demonstrate for the first time that inhibition of the ECM-induced Erk 1/Erk 2 (p42/44 MAPK) pathway, by PD 98059, leads to apoptosis in these cells. Associated with this cell death is a possible compensatory signalling through the p38 MAP kinase pathway the inhibition of which, by SB 203580, leads to a more rapid onset of apoptosis. This provides evidence for a hitherto undescribed Erk 1/Erk 2 to p38 MAP kinase pathway 'cross-talk' that is essential for the survival of these cells. The cell death associated with inhibition of these two MAP kinase pathways however, occurred in the presence of insulin that activates the classical PI-3 kinase-dependent Akt/PKB survival signals and Akt phosphorylation. Cell death induced by inhibition of the MAP kinase pathways did not affect Akt phosphorylation and may, thus, be independent of PI-3 kinase signalling.

Animals↗
PubMed2000

Cortical motor reorganization in akinetic patients with Parkinson's disease: a functional MRI study.

Using functional MRI (fMRI), we have studied the changes induced by the performance of a complex sequential motor task in the cortical areas of six akinetic patients with Parkinson's disease and six normal subjects. Compared with the normal subjects, the patients with Parkinson's disease exhibited a relatively decreased fMRI signal in the rostral part of the supplementary motor area (SMA) and in the right dorsolateral prefrontal cortex, as previously shown in PET studies. Concomitantly, the same patients exhibited a significant bilateral relative increase in fMRI signal in the primary sensorimotor cortex, lateral premotor cortex, inferior parietal cortex, caudal part of the SMA and anterior cingulate cortex. These fMRI data confirm that the frontal hypoactivation observed in patients with Parkinson's disease is restricted to the rostral part of the SMA and to the dorsolateral prefrontal cortex. These results also show that, apart from the lateral premotor and parietal cortices, increased fMRI signals can be found in other cortical motor areas of these patients, including the posterior SMA, the anterior cingulate cortex and the primary sensorimotor cortices, which are then likely to participate in the same putative attempt by the dopamine-denervated brain to recruit parallel motor circuits in order to overcome the functional deficit of the striatocortical motor loops.

Aged↗
PubMed2000

Scintigraphic evolution of a breast cancer with Tc-99m MIBI scintimammography.

Early detection and prompt treatment of breast cancer are the main tools to decrease mortality rates. Several diagnostic techniques such as mammography, magnetic resonance imaging, and ultrasound are used, but none of these are conclusive. The authors describe a 56-year-old woman who was suspected of having breast cancer on mammography. Tc-99m MIBI scintimammography showed a small mass with elevated radiotracer uptake located near the pectoral muscle of the patient's left breast. The possible tumor was confirmed with fine-needle aspiration biopsy. After the diagnosis was established, the patient did not allow any treatment. Eighteen months later, a second scintimammography was performed, showing a large mammary tumor with a high radiotracer uptake, a new small lesion located in the left upper quadrant, and axillary lymph node involvement. Chemotherapy treatment was instituted and after treatment, Tc-99m MIBI scintimammography was normal. This case report provides further evidence for Tc-99m MIBI scintimammography for the detection of breast cancer as well as to evaluate the response to chemotherapy.

Antibiotics, Antineoplastic↗
PubMed2000

Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.

Adult↗
PubMed2000

Analytical solution for the covariance and for the decorrelation time of the angle of arrival of a wave front corrugated by atmospheric turbulence.

The two-dimensional (2D) spatial covariance of the angle-of-arrival (AA) fluctuations is often used to investigate the properties of wave fronts corrugated by the atmosphere for high-angular-resolution techniques. Theoretical series expansions of this covariance are presented. The fast convergence of these series reduces the calculation time of the covariance done by numerical integration. The 2D covariance is a nonradial function. A physical interpretation of this anisotropy is proposed. The spatiotemporal correlation of the AA is deduced from the covariance assuming the "frozen-flow" hypothesis. The impact of the anisotropy on the evaluation of the number of predominant turbulent layers and on the corresponding winds is investigated, and an analysis of temporal correlations is performed. A simple theoretical approximation of the decorrelation time of the AA is given, which is found to be in agreement with experimental results.

Journal Article↗
PubMed2000

P300, N400, aerobic fitness, and maximal aerobic exercise.

Electrophysiological effects of aerobic fitness and maximal aerobic exercise were investigated by comparing P300 and N400 before and after a maximal cycling test. Event-related potentials (ERPs) were obtained from 20 students divided into two matched groups defined by their aerobic fitness level (cyclists vs. sedentary subjects). The session of postexercise ERPs was performed immediately after body temperature and heart rate returned to preexercise values. At rest, no significant differences were observed in ERP parameters between cyclists and sedentary subjects. This finding argued against the hypothesis that ERP modifications may be directly assumed by aerobic fitness level. The postexercise session of ERPs showed a significant P300 amplitude increase and a significant P300 latency decrease in all subjects. Similarly, N400 effect increased significantly after the maximal exercise in all subjects. ERP changes were of the same magnitude in the two groups. The present study argues for a general arousing effect of maximal aerobic exercise, independently of the aerobic fitness level.

Adolescent↗
PubMed2000

B-cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells as part of a "natural immune memory".

The rate of elimination of a pathogenic agent is of critical importance for the host and determines the extent and consequences of the infection. Antibody production, along with the activity of other cells of the immune system, plays an important role early and late in the response and contributes to all containment and elimination of the organism. B-cell clones reaching the mature long-lived pool are heterogeneous: some belong to the B1 B-cell subset, some are enriched in the CD21high compartment (mostly marginal zone (MZ)), whereas others recirculate primarily among the B-cell follicles (FO). This segregation is a T-independent, CD40L-independent but BCR/CD19-dependent process. Antigen encounter will recruit antigen-specific cells from the pool of mature B-lymphocytes and activate them to perform effector functions. CD21highCD23low B cells enriched in the MZ of the spleen initiate the early plasmablast wave during the first 3 days of an antibody response against particulate T-independent bacterial antigens. These findings indicate a functional heterogeneity within the mature B-lymphocyte population. MZ B cells and B1 B, in contrast to FO B cells, have the unique capacity to generate effector cells in early stages of the immune response against (particulate) antigens that are scavenged efficiently in these specialized anatomical sites.

Animals↗
PubMed2000

GM-CSF expression by tumor cells correlates with aggressivity and with stroma reaction formation.

Granulation tissue involved in tissue repair and in the stroma reaction to epithelial tumors is characterized by the presence of myofibroblastic cells. It has been previously reported that granulocyte macrophage-colony stimulating factor (GM-CSF) induces a fibrotic reaction containing numerous myofibroblasts. This reaction results from a cascade of events, including stimulation of transforming growth factor-beta1 (TGF-beta1) production by macrophages which, in turn, promotes alpha-smooth muscle actin and collagen synthesis by fibroblasts. Moreover, GM-CSF is known to be expressed by many tumor cell types. In this study we have analyzed, by means of reverse transcription-polymerase chain reaction, GM-CSF mRNA expression in a progressive and a regressive rat colon carcinomas and in the corresponding cell lines, eliciting different degrees of desmoplastic reaction. We have also evaluated the expression of GM-CSF protein in selected cases. The expression of GM-CSF mRNA and, when tested, protein were higher in progressive compared to regressive cancer cells both in vivo and in vitro. We then investigated GM-CSF mRNA and protein expression in different human colon cancer cell lines known to exhibit different degrees of aggressivity in vivo. We found high levels of GM-CSF mRNA and protein in the most aggressive cell lines. Similar results were also obtained on human breast and cervical cancer cell lines. Our results are in agreement with the assumption that GM-CSF expression is correlated to tumor aggressivity. Conceivably, one of the GM-CSF actions affecting tumor progression is exerted through its influence on stroma reaction development.

Animals↗
PubMed1999

FAS(CD95) ligand expression by tumor cell variants can be unrelated to their capacity to induce tolerance or immune rejection.

According to the results of in vitro experiments, Fas(CD95) ligand expression by cancer cells might induce apoptosis of activated T cells and contribute to immune tolerance. However, Fas ligand expression had never been explored in vivo in tumor cell models yielding either immune response or tolerance. In the present study, we analyzed the expression and function of Fas ligand in 2 clones of tumor cells originating from the same rat colon carcinoma. REGb cells were immunogenic and yielded tumors that regressed in immunecompetent syngeneic hosts, whereas PROb cells induced active tolerance and yielded progressive tumors. Fas ligand was expressed on the plasma membrane of both REGb and PROb cells, and its cDNA sequencing showed no mutation. However, neither REGb nor PROb cells induced apoptosis of co-cultured Fas-sensitive target cells. Our results show that surface expression of Fas ligand by tumor cells does not always induce killing of adjoining Fas-sensitive cells and that tumor cells may induce a protective immune response or an active tolerance independently of Fas ligand expression.

Animals↗