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Biomedical subjects

M Ffrench

Publications and source records attributed to M Ffrench.

At least 37 records · Page 2Linked to original sources
PubMed1996

Australian Vietnam veterans: factors contributing to psychosocial problems.

OBJECTIVE: The objective of the present paper is to present comprehensive models of the current psychosocial morbidity of Australian Vietnam veterans. Seldom has research in this area attempted to 'untangle' direct and indirect influences on current functioning via possible pre-army, Vietnam and homecoming pathways. METHOD: The Australian Vietnam Veterans' Health Study gathered data on a sample of 641 veterans throughout Australia drawn randomly from army Vietnam tour lists of the era. The data arose from interview and army records of the era, and fall into four temporal categories: pre-army, Vietnam service, homecoming after Vietnam, and current state. Path analysis models of the veterans' current psychological morbidities and social wellbeing are used to identify direct aetiological influences of earlier era constructs on current state, free of confounding by indirect (often selection) effects. RESULTS: Our results indicate that psychological morbidity (particularly posttraumatic stress disorder) is largely influenced by combat and poor homecoming experiences, although pre-military characteristics do play some direct roles in symptomatology. Social dysfunction measures show smaller effects of the Vietnam War, which may be accounted for by an indirect association with Vietnam-related psychological morbidity. Some social measures show evidence of compensatory influences of combat, high combat leading to social dysfunction because of morbidity, but simultaneously being associated with healthier social disposition (possibly because of increased exservice activity). CONCLUSIONS: For Australian Vietnam veterans, combat-related and homecoming effects persist on a range of psychosocial endpoints 20-30 years after exposure. These effects are not explicable in terms of veterans pre-Vietnam characteristics.

Adolescent↗
PubMed1995

Methods for cell proliferation analysis by fluorescent image cytometry.

Methods were developed for multimodal microscopic image analysis in order to identify and analyze one cell type under various microscopic conditions. Our purpose was to quantify both total DNA content using propidium iodide (PI) stain and S-phase fraction using the bromodeoxyuridine (BrdUrd) incorporation technique in cell population subsets. The model chosen was plasma cells in bone marrow triply labelled with fluorescein isothiocyanate (FITC) for intracytoplasmic immunoglobulins, with amino-methylcoumarin-acetate (AMCA) for BrdUrd, and with PI for DNA. Image analysis included three phases. First, plasma cells were recognized on FITC images, and the centroid positions were stored. Second, plasma cell nuclei were geodesically reconstructed from these stored positions using PI images in which DNA content was measured, and the nuclear mask outlines were stored. Third, BrdUrd incorporation level of plasma cells was measured on AMCA images inside PI nuclei masks and stored. Image DNA vs. BrdUrd scatterplots were obtained for cells selected according to the expression of intracytoplasmic immunoglobulin. Thus, both ploidy and proliferation could be independently evaluated on a subset of the cellular population.

Animals↗
PubMed1995

Cdk1 is a marker of proliferation in human lymphoid cells.

To better understand the relationship between the proliferation of human lymphoid cells and the expression of cdk1, a catalytic subunit of the histone H1 kinase (H1K), we examined its mRNA and protein content in 3 B-cell lines: Ramos, Reh-6 and IARC 963. Cells were elutriated according to their position in the cell cycle. Cell fractions were analyzed for cdk1 mRNA and protein cellular content by Northern blot and immunoblot, respectively, as well as for H1K activity. Both mRNA and protein amounts and H1K activity varied according to cell cycle phase, the lowest values being observed in G1-enriched fractions. For comparison, elutriated fractions were also tested for the expression of cdk2 and cdk4 proteins. Both showed some variations among fractions, but they were less clear than those of cdk1. We also tested 29 samples of lymphoid neoplastic and non-neoplastic tissues for proliferative activity (percentage of S and G2/M cells estimated by flow cytometry) and expression of cdk1, cdk2 and cdk4 proteins. We found a significant correlation between the percentage of cells in S or S + G2/M phases and cdk1 protein content but not cdk2 or cdk4 content. We conclude that cdk1 expression in human lymphoid cells varies during the cell cycle at both mRNA and protein levels.

Biomarkers↗
PubMed1995

Plasma cell proliferation in monoclonal gammopathy: relations with other biologic variables--diagnostic and prognostic significance.

PURPOSE: We investigated the place of direct plasma cell proliferation analysis beside other biologic data in monoclonal gammopathy, particularly the serum level of C-reactive protein (C-RP) PATIENTS: Eighty patients were studied at the time of their diagnosis. Patients with a serum creatinine level greater than 200 mumol/L were excluded. METHODS: Plasma cell proliferation analysis was performed after bromodeoxyuridine incorporation and double immunoenzymatic labeling on cytological smears, making determination of the plasma cell labeling index (LI) possible. The other biologic variables studied were related to tumor burden (plasmacytosis, hemoglobin, serum levels of monoclonal immunoglobulin, albumin) or to kidney function (creatinine). beta 2-microglobulin (beta 2-M), C-RP, lactic dehydrogenase (LDH), and calcemia were also assessed. RESULTS: No correlation was found between LI and serum C-RP. LDH was the sole variable significantly correlated to C-RP (P < 0.01). Besides the biologic parameters used for the staging according to the Durie and Salmon classification, beta 2-M, albumin and LI were significantly different between stages (P < 0.0002, < 0.0004, < 0.00001). LDH and C-RP showed no significant difference. Results were similar when patients with and without bone lesions were analyzed separately. Multivariate analysis ranked these variables as follows with respect to prognostic value: beta 2-M, LI, and age. CONCLUSION: Among the variables analyzed, LI is the sole true reflector of cell proliferation. We confirm its diagnostic and prognostic value.

Adult↗
PubMed1995

Post-transplant lymphoproliferative disorders with genetic abnormalities commonly found in malignant tumours.

Post-transplant lymphoproliferative disorders (PTLD) are potentially fatal complications of organ transplants. Impairment of the immune system by immunosuppressive drugs is the assumed cause of PTLD. The Epstein-Barr virus (EBV) is detected in most of the PTLD studied and is considered as the main aetiological agent. The clinical course of PTLD patients remains unpredictable, some lymphoproliferations regress after discontinuation of the immunosuppressive treatment, others behave as true malignant tumours. The mechanism by which a viro-induced lymphoproliferation evolves to an autonomous tumour remains unclear, and little is known about the genetic changes that occur during this process. We report two cases of fatal EBV-associated PTLD in heart transplant recipients. Both tumours were monoclonal and carried numerous chromosomal abnormalities, including a classic t(8;14)(q24;q32) with rearrangement of the MYC proto-oncogene. One tumour demonstrated an amplification of the proto-oncogene N-MYC. The EBNA2 gene was not expressed in tumoral cells, suggesting that the chromosomal abnormalities contributed the function of EBNA2 in these cells. The morphology of the tumours indicated that the cases presented here were not Burkitt's lymphomas. These findings provide some clues with regard to the genetic changes which lead to a B-cell malignancy in some transplant patients.

Adult↗
PubMed1995

Expression of cell cycle regulatory proteins in chronic lymphocytic leukemias. Comparison with non-Hodgkin's lymphomas and non-neoplastic lymphoid tissue.

The expression of certain cell cycle regulatory proteins: cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin E, Bcl2 and PCNA was examined in peripheral blood lymphocytes (PBL) from 25 cases of chronic lymphocytic leukemias (CLL) in order to analyze a possible cell cycle involvement of CLL lymphocytes. For comparison, we also studied the expression of these proteins in: 23 samples of non-Hodgkin's lymphoma (NHL) tissue of different histological types, 10 samples of non-neoplastic lymphoid tissue (NLT), non-stimulated PBL (NS-PBL) and PHA-stimulated PBL (PHA-PBL) from three healthy donors. Samples were lysed and proteins were resolved on polyacrylamide gel followed by Western blot. The expression of cdk4 and cyclin E, both known to act in early cell cycle stage, was approximately on the same level in all groups of lymphoid pathology examined. In particular, we found that that 19 out of 24 CLL cases were cyclin E positive and all but one were cdk4 positive, ie they expressed these markers over twice the level of non-stimulated healthy PBL. The cdk1 expression was above the level seen in NS-PBL in 14 (56%) cases, but the average expression was significantly lower than in the other tissues examined, including low-grade lymphomas. Cdk2 expression was comparable in CLL and in low malignancy grade NHL, but weaker than in other NHL and in NLT. Cyclins A and B, normally observed in advanced cell cycle phases, were not seen in any CLL case. The presence of cdk4 and cyclin E in the blood cells of the majority of CLL cases studied, as well as cdk1 and cdk2 in some cases, indicate that the CLL cells are not quiescent, but are blocked in an early stage of the G1 cell cycle phase, and/or that the expression of these proteins is pathologically deregulated.

Adult↗
PubMed1994

Choice of fixation and denaturation for the triple labelling of intra-cytoplasmic antigen, bromodeoxyuridine and DNA. Application to bone marrow plasma cells.

A triple staining method of intra-cytoplasmic antigen, bromodeoxyuridine (BrdU), and DNA for fluorescence image analysis is described. Several kinds of fixation and DNA denaturation methods were tested to obtain a technique suitable for heterogeneous tissues. The model chosen was the analysis of plasma cells in bone marrow. The fluorochromes used were fluorescein isothiocyanate (FITC) for intra-cytoplasmic antigens (light chain immunoglobulins), aminomethylcoumarin acetic acid (AMCA) for BrdU, and propidium iodide (PI) for DNA. The quality of the staining was analysed according to: (1) cell morphology with a good preservation of the chromatin structure, (2) intensity of light chains and of BrdU labelling, and (3) the quality of DNA staining judged from a DNA histogram. For most of the analysed tissues, fixation with methanol followed by 0.5% paraformaldehyde and denaturation by an NaOH concentration adapted to the tissue gave good results. However, in our model fixation by methanol, followed by methanol/acetic acid and denaturation of DNA by 0.03 N NaOH was the solely satisfactory technique. A good correlation (P < 0.001) was found with the plasma cell BrdU labelling index obtained with our reference immuno-enzymatic technique. Quantification of DNA content showed a satisfactory G1 peak coefficient of variation (CV) in diploid cells and a 4C to 2C ratio equal to 2. With this technique, the nuclear and cytoplasmic structures of both myeloid cells and plasma cells were well preserved, while their sensitivity to DNA denaturation was quite different.

Antigens↗
PubMed1994

Heterogeneity of neoplastic and reactive cell proliferation in non-Hodgkin's lymphomas linked to patient survival.

This study was undertaken to determine the characteristics of the proliferation of malignant and reactive cells in non-Hodgkin's lymphoma (NHL). Cell kinetics were studied in 76 previously untreated cases of NHL by flow cytometry after a double labeling of membrane antigen and DNA. Results were analyzed according to clinical and biologic characteristics of the patients. In B-cell NHL, percentages of B and T cells in S-phase were strongly linked (r = .82). The level of proliferation of malignant B cells and reactive T cells was significantly higher in aggressive lymphomas, compared with low grade, diffuse small cleaved cell NHL or reactive lymph nodes (P < .001). The percentages of malignant B cells in S-phase were lower when reactive T cells were more numerous (n = 59, r = -.264, P < .05), particularly in high-grade NHL (n = 16, r = -.78, P < .001). In the whole population of patients, survival was longer when the percentage of cells in S-phase (n1 = 38, n2 = 33) or S+G2 + mitosis (M) (n1 = 36, n2 = 35) was less than 3.2% and 7.25%, respectively (P < .005). When considering only B-cell NHL, survival was longer when the percentage of B cells in S-phase was less than 4.5% (n1 = 31, n2 = 28, P < .04). Among the slowly proliferative groups of lymphomas, this prognostic value was retained when S-phase value was less than 1% (n1 = 16, n2 = 13, P < .002). Furthermore, prognosis was better when the percentage of T cells in S-phase was less than 2.75% (n1 = 30, n2 = 29, P < .01) or when reactive CD4-positive T cells were more than 14.5% (n1 = 24, n2 = 24, P < .04). This result remained true in the group of highly proliferative lymphomas. These results illustrate the complexity of the interactions between malignant and reactive cells in NHL, with possible opposite effects on tumor cell growth.

Adolescent↗
PubMed1994

Expression of adhesion molecules in endothelial cells during allogeneic bone marrow transplantation.

Endothelial cell activation during allogeneic bone marrow transplantation, mainly in acute graft-versus-host disease (aGvHD) was studied in 23 recipients and 5 controls using anti-von Willebrand factor (vWF) antibody, antibodies to endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and anti-HLA-DQ antibody, by immunohistological staining of skin. vWF extravasation, ELAM-1 and VCAM-1 expression were present in most recipients with a cutaneous rash which was confirmed as an aGvHD by histological examination (documented aGvHD) (p = 0.005 for vWF extravasation and ELAM-1 expression and p = 0.03 for VCAM-1 expression in comparison with the controls). In recipients with a rash, the cases displaying vWF extravasation and ELAM-1 expression were significantly more numerous in those with a documented aGvHD than in those without histological features of aGvHD (p = 0.01). vWF extravasation and ELAM-1 occurred concomitantly (p < 0.01). This study demonstrates that, during the course of skin aGvHD following bone marrow transplantation, there is transient expression of ELAM-1 and VCAM-1 by endothelial cells and simultaneous vWF extravasation, indicating an intense inflammation with endothelial cell participation.

Acute Disease↗
PubMed1994

Fluorescence image analysis of plasma cells in monoclonal gammopathies.

The DNA content of plasma cells was estimated by fluorescence image analysis in monoclonal gammopathies. Image analysis provides the possibility of measuring the bone marrow plasma cell population separately from the other myeloid cells. Plasma cells were labeled, identified and then relocated for propidium iodide intensity measurements. Patients with DNA malignancy grade > 0.20 or with DNA index > 1.15 had a poorer survival rate than did patients with a low DNA malignancy grade or DNA index. DNA malignancy grade is based on the variance of DNA values around the normal diploid peak, as proposed by Böcking. Of all the biologic and clinical parameters investigated, the serum beta 2 microglobulin level was the most important prognostic factor for survival in the multivariate regression analysis, and the DNA entropy index provided the most significant additional information.

Aged↗
PubMed1993

Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias.

The t(11;14)(q13;q32) translocation and its molecular counterpart, BCL-1 rearrangement, are consistent features of intermediate lymphocytic lymphoma (ILL). Rearrangement is thought to deregulate the nearby PRAD-1/BCL-1 proto-oncogene that is a newly identified member of the cyclin family. To characterize further the association between rearrangement of chromosome 11q13 and over-expression of BCL-1. Southern blot analysis was performed in 33 cases of ILL, 5 cases of t(11;14)-associated leukemias, and 1 case of leukemia carrying a variant translocation t(11;19)(q13;q13) using three separate BCL-1 locus probes. When RNA was available, BCL-1 expression was assessed by Northern blot analysis. DNA from 19 of 33 ILL (57%) showed BCL-1 rearrangement, 16 involving the major translocation cluster (MTC) region and 3 involving a new breakpoint cluster located in the 5' flanking region of the BCL-1 gene. DNA from 3 of 6 t(11q13)-associated leukemias demonstrated a rearrangement involving the MTC. Northern blot analysis showed that BCL-1 was overexpressed in 14 of 15 ILL and in all leukemias analyzed (included the t(11;19) leukemia) relative to normal and malignant lymphoid tissues. These results constitute additional elements in favor of the role of BCL-1 in lymphoid neoplasia and allow us to speculate about its mechanisms of activation.

Aged↗
PubMed1993

Wegener's granulomatosis with antiproteinase-3 antibodies occurring after Hodgkin's disease.

We describe the first association between Hodgkin's lymphoma and Wegener's granulomatosis, heralded by renal involvement. A 43-year-old man developed rapidly progressive glomerulonephritis requiring chronic hemodialysis 8 months after remission of Hodgkin's lymphoma. At that moment, no extrarenal involvement was found, despite extensive investigation. Antineutrophil cytoplasm antibodies were positive, without specificity for proteinase-3 or myeloperoxydase. Six months after beginning hemodialysis, multiple pulmonary nodules appeared, along with rapid clinical worsening. A surgical biopsy was performed which disclosed a giant cell granuloma. Antimyeloperoxydase antibodies remained negative, whereas proteinase-3 antibodies became positive. Wegener's granulomatosis was diagnosed and treatment with cyclophosphamide and steroids was started. Clinical and radiological improvement occurred promptly. Eleven months after treatment, both Wegener's disease and Hodgkin's lymphoma remained in remission.

Adult↗
PubMed1993

Comparison of anti-fading agents used in fluorescence microscopy: image analysis and laser confocal microscopy study.

To ascertain the ability of commercial and home-made anti-fading media to reduce the decrease of fluorescein isothiocyanate (FITC) fluorescence, we studied the bleaching characteristics of FITC-stained Reh 6 cells mounted in buffered glycerol and in anti-fading media. We measured the intensity of fluorescence over time with a confocal laser scanning microscope and a standard epifluorescence microscope coupled to an image analysis system. Most of the anti-fading media effectively retard fading but each has drawbacks. Better results were obtained with media containing p-phenylenediamine (solutions in buffered glycerol, Vectashield, Fluorstop). However, Mowiol, Slowfade, n-propyl gallate (20 g/liter) were also effective in retarding fading. Most of them, except Mowiol, reduced fluorescence intensity. We concluded that the choice of anti-fading medium would depend on the desired results: a slower decay of fluorescence despite an initial quenching of fluorescence or a lower retardant effect with no decrease in initial fluorescence intensity. Moreover, the combination of Mowiol with another anti-fading medium may be a useful compromise when a strong retardant effect is required without marked quenching of the initial fluorescence.

Animals↗
PubMed1993

[Mitotic cyclins--new possibilities for examining mechanisms of neoplasm growth].

Mitotic cyclins constitute a regulatory subunit of the histone H1 kinase complex. On the ground of their primary structure they are divided into two classes A and B, both necessary for the mitosis. Cyclin A activates histone H1 kinase and becomes destroyed by proteolysis earlier than cyclines B and plays an important role in the DNA replication. Cyclins A and B may be involved in the development of neoplastic disorders either directly (inappropriate expression of the cyclin A gene caused by hepatitis B virus in hepatocellular carcinoma, or interactions of this cyclin with factors participating in the regulation of cell proliferation) or indirectly by phosphorylation of some oncogene or antioncogene proteins by a cdk (cyclin dependent kinase).

Animals↗
PubMed1993

[Cyclins A and B: redundancy and specificity].

Mitotic cyclins constitute a regulatory subunit of the histone H1 kinase complex. On the basis of primary structure differences, they are divided into two classes, A and B. Both classes are necessary for mitosis to occur. Cyclins A and B differ in the timing of their cellular expression and in their affinity with the various members of the cdk (cyclin-dependent kinases) family. They also have specific functions: cyclin A plays a role in DNA replication, whereas cyclin B are involved in the inhibition of the fusion of early endosomes and in the activation of cdc25 phosphatase. Cyclins A and B can contribute to the development of neoplastic disorders, either directly (inappropriate expression of the cyclin A gene caused by the hepatitis B virus in hepatocellular carcinoma, interactions between cyclin A and factors involved in the regulation of cell division), or indirectly by causing phosphorylation of oncogene products by a cdk.

CDC2 Protein Kinase↗
PubMed1992

BTG1, a member of a new family of antiproliferative genes.

The BTG1 gene locus has been shown to be involved in a t(8;12)(q24;q22) chromosomal translocation in a case of B-cell chronic lymphocytic leukemia. We report here the cloning and sequencing of the human BTG1 cDNA and establish the genomic organization of this gene. The full-length cDNA isolated from a lymphoblastoid cell line contains an open reading frame of 171 amino acids. BTG1 expression is maximal in the G0/G1 phases of the cell cycle and is down-regulated when cells progress throughout G1. Furthermore, transfection experiments of NIH3T3 cells indicate that BTG1 negatively regulates cell proliferation. The BTG1 open reading frame is 60% homologous to PC3, an immediate early gene induced by nerve growth factor in rat PC12 cells. Sequence and Northern blot analyses indicate that BTG1 and PC3 are not cognate genes. We then postulate that these two genes are the first members of a new family of antiproliferative genes.

3T3 Cells↗