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C Fournel

Publications and source records attributed to C Fournel.

At least 19 recordsLinked to original sources
PubMed2000

Canine large granular lymphocyte leukemia and its derived cell line produce infectious retroviral particles.

We describe a case of large granular lymphocyte (LGL) leukemia in a dog that we followed over a period of 2 years. Analysis of a hematological profile revealed lymphocytosis (19,500 lymphocytes per microliter; reference values, 1,000-4,800 lymphocytes per microliter), with a majority of LGL on the blood smear. LGL is defined as a lymphoid subset comprising 10% of peripheral blood mononuclear cells and corresponding to either CD3- CD8- NK cells or CD3+ CD8+ T cells. The cells are characterized by abundant basophilic cytoplasm containing distinct granules of variable size and number. The characteristic phenotype of our leukemic LGL is of a cytotoxic T cell, CD3+ and CD8+. A new cell line, DLC 02, was established from the peripheral lymphocytes of the leukemic dog. Particles with type C retroviral morphology were found in ultrathin sections of DLC 02 cell pellets. These particles were found to have a sucrose gradient density of 1.17 g/liter and a reverse transcriptase activity with an Mn2+ preference, suggesting that they correspond to a mammalian type C oncovirus.

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PubMed1999

Characterization of a canine long-term T cell line (DLC 01) established from a dog with Sézary syndrome and producing retroviral particles.

The canine DLC 01 cell line derives from a lymph node of a dog with Sézary syndrome. The DLC 01 cell phenotype is CD4-, CD8+, CD45+, DQ+, similar to that of original cells after treatment with dimethylsulfoxide or phorbol myristate. Canine cutaneous T cell lymphoma are usually CD4-, CD8+ in contrast to their human counterparts which are CD4+, CD8-. Therefore, the DLC 01 cell line appears to be a unique model to study the mechanism of all surface molecule expression in vitro. Viral particles with retrovirus type-C morphology were found in ultrathin sections of DLC 01 cell pellets. Retroviral particles are spontaneously produced after the 50th cell passage or after induction with 0.5% dimethylsulfoxide. This is the first description of a dog lymphoid cell line spontaneously growing and producing a retrovirus. It was found to share several features in common with feline and murine leukemia viruses.

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PubMed1996

[Clinical, morphologic and immunophenotypic data based on 10 cases of canine muco-cutaneous epidermotropic T-lymphoma (analogous to Mycosis Funcgoïde). Important of an animal model of spontaneous pathology].

Our serie of ten canine cutaneous epitheliotropic T-cell lymphomas (CTCL), is found in old dogs, belonging mainly to the Boxer breed. Site on the mucous membranes (especially buccal), the muco-cutaneous junctions, their clinical expression is polymorphous. Lesions, follow on one after another (erythema, plaques, nodules) and are diversely associated in a given animal, the borders between the different stages often being difficult to establish. Adenopathies noted at the time of the diagnosis or during the course of the condition are accompanied by an involvement of the blood and organs (analogous to Sézary's disease). The progression of the disease can be very rapid in the buccal forms, which are generally aggressive, and in cases of violent, uncontrollable pruritus, which may be disturbing for the owner (with requests for euthanasia). The neoplastic infiltrate is constituted of small lymphocytes with hyperchromatic, convoluted nuclei (incipient stages), then large cells with a "histiocytic" appearance for the nodules. Epitheliotropism, which is maximal for the infiltrated plaque stage, shows up either in the form of a flux of totally epitheliotropic isolated cells (Ketron-Goodman type) or in that of Pautrier abscess-like collections. THe veterinary literature is in agreement that the CTCL cell expresses CD3, but two recent studies are in contradiction as regards its membership of helper or cytotoxic/suppressor populations. For our 10 cases, all the cells of lymphocytic morphology were, without exception, CD3+ and CD45+, irrespective of their situation within the epithelium or the chorion. The CD3+ cells in the epithelium were systematically CD8+, CD4- (confirming P.F. Moore's observations), expressing CD5 in a variable way, and, mostly, the Ki-67 nuclear proliferation Ag. The CD3+ cells of the chorion were exclusively, or mainly, CD8+, and occasionally CD4+. They expressed CD5 in a variable way, and, for a minority, the Ki-67 nuclear proliferation Ag. On the pathogenic level, it may be suggested that a T clone, CD8+, undergoes the "homing" phenomenon within the epithelium, enters the cell cycle, then manifests a tropism towards the chorion, which it infiltrates. Despite some particularities, which may be clinical (serious mucous attacks), cytological (the "histiocytic" appearance of the nodule cells) or immunophenotypic (expression of CD8, similar to what is observed in man in a considerable number of Pagetoid reticulosis), CTCL constitutes an interesting model of spontaneous pathology, and could prove useful in: - identifying various etiological factors (given that the dog, as a close commensal of man, is subject to the same environmental factors).

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PubMed1995

Lymphocyte subset abnormalities in German shepherd dog pyoderma (GSP).

Peripheral blood lymphocyte subpopulations were studied in 12 German shepherd dogs suffering from deep pyoderma (GSP). Twelve other healthy but matched dogs were used as controls. GSP was found to be associated with an imbalance in the CD4 and CD8 subsets (respectively 37.3 +/- 8.7% and 28.6 +/- 6.6%, as compared to 47.5 +/- 8.8% and 19.3 +/- 4.0% in the controls). The activation markers were not affected by GSP. Moreover, analysis of the B-cell populations showed a striking decrease in the level of CD21 cells (5.5 +/- 3.3% of CD21+ lymphocytes, compared to 12.2 +/- 6.0 in the controls). This study suggests that the immunological imbalance observed in GSP may be associated with defective helper cells, and provides further evidence that dogs suffering from GSP are not immunologically normal reactors.

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PubMed1995

An original perifollicular zone cell in the canine reactive lymph node: a morphological, phenotypical and aetiological study.

In this study of 109 canine reactive lymph nodes, the perifollicular zone (PZ) cell was characterized by cytological, histological, immunocytochemical and electron microscopical techniques. The PZ cell was always found in association with plasma cell hyperplasia. Its main cytological characteristics were medium size, fine chromatin and a large central prominent nucleolus with a small amount of pale cytoplasm. It was located in a clearly recognizable PZ surrounding the follicles; this zone was particularly well developed at the capsular pole of the lymph node. Electron microscopical findings indicated a poorly differentiated cell. Immunolabelling indicated a CD3-, cIg-, Ki-67- immunophenotype, suggesting a resting B cell. These results suggest that the PZ cell belongs either to a post-follicular stage between large immunoblasts and plasma cells or, as is more likely, to a pre-follicular lymphoid subpopulation occurring early in the B-cell differentiation scheme, as with most human marginal zone (MZ) cells. Its high frequency of occurrence in reactive lymph nodes in mammary tumour lymphadenopathies, systemic lupus erythematosus and leishmaniasis, suggests that the PZ cell has a special role in the canine immune response, or perhaps in the arrested maturation of the normal developmental process.

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PubMed1995

Immunophenotypic and ultrastructural evidence of the langerhans cell origin of the canine cutaneous histiocytoma.

Canine cutaneous histiocytoma (CCH), a histiocytic benign, dermal, self-healing tumor in the young dog, and epidermal Langerhans cells (LC) are thought to be related. In this study, we used immunohistochemical staining and transmission electron microscopy for 5 fresh CCH and 17 fixed tumors, to examine if, on the basis of their immunophenotype and their ultrastructural morphology, these tumor cells originate as LCs. The immunophenotype of CCH: canine CD11a, 11c, 18, 45, MHC II positive and ACM1, human CD14 negative, was different from canine macrophage immunophenotype but very similar to the canine LC phenotype. Furthermore, we have described ultrastructural markers in CCH cells for the first time: these consist of coated vesicles, regularly laminated bodies, pleiomorphic inclusions, paracrystalline structures, and deep invaginations of the plasma membrane, usually observed in congenital self-healing histiocytosis, a human LC tumor, or occasionally observed in human LC. The occurrence of such immunophenotype and ultrastructural markers confirmed the common lineage of LCs and CCH cells.

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PubMed1995

Abnormalities of lymphocyte subsets in canine systemic lupus erythematosus.

Canine systemic lupus erythematosus (SLE) is a disease clinically very similar to its human counterpart. But so far, no study has reported an accurate evaluation of the lymphocyte subsets in the canine disease. Here, we present a study in which lymphocyte subsets have been evaluated in the peripheral blood of 20 dogs suffering from spontaneous systemic lupus erythematosus (SLE) in active and inactive phases, before and during treatment with prednisone and levamisole. 22 healthy dogs have been used as a control population. We show that canine SLE in active phases is associated with a several lymphopenia (1050 +/- 520 10(6) cells/l versus 2130 +/- 1 020 10(6) cells/l in controls). A striking finding is the imbalance of the CD4 and CD8 subsets (respectively 56.7 +/- 10.7% and 10.9 +/- 3.8% of CD4+ and CD8+ lymphocytes versus 40.5 +/- 11.5% and 18 +/- 4.4% in controls) and a strong activation of T-cells in active phases (64.1 +/- 16.9% of 2B3+ cells versus 46.5 +/- 16.7%). Moreover, we observed a persistence of the T subset imbalance during spontaneous evolution. In contrast, the treatment induced in dogs showing a good response the correction of CD4/CD8 ratio and no clinical manifestations, whereas in low responders no such improvements were observed. Thus, this work suggests that the main immunological imbalance seen in SLE could be associated with defective suppressor cells and provides further evidence of similarity of human and dog SLE.

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PubMed1995

[Malignant lymphoma with medium-sized macronucleolated cells in the dog: involvement of an original cell from the marginal zone of the reactive lymph node].

Among the non-Hodgkin's malignant lymphomas of the dog, which are largely dominated by the centroblastic heterogeneous type, there is an original form of malignant lymphoma which is homogeneous and diffuse, with macronucleolated medium-sized cells. These cells seem to be morphologically very similar to those which constitute the majority population in the marginal zone of the secondary follicle of the lymph node in the dog, and which appear in the course of certain conditions: systemic lupus erythematosus, leishmaniasis, satellite lymph nodes in benign or malignant tumors. The aim of this study was twofold: on the one hand to establish, in the canine species, the identity of the lymphomatous cells and the reactive cells that make up the marginal zone, i.e. the filiation between the hyperplastic marginal zones and the macronucleolated malignant lymphoma with medium-sized cells, and, on the other hand, to compare this type of malignant lymphoma with those which are reputed to originate in the marginal zone in humans, for example the malignant lymphoma of the lymphoid tissue associated with the mucous membranes, and the monocytoid malignant B-cell lymphomas. Ninety four malignant lymphomas were observed between 1989 and 1994 at the Veterinary School in Lyon; these consisted of 71 cases showing medium or high-grade malignancy, 17 cases with small cells, of low-grade malignancy, and 6 cases of mycosis fungoides. Among the 71 cases of medium and high-grade malignancy, 8 were immunoblastic, 5 centroblastic homogeneous, 50 centroblastic heterogeneous, and 8 homogeneous with macronucleolated medium-sized cells. The methods used in these 94 cases were of a morphological type: cytology, histology, transmission microscopy and immunohistochemistry. The cytohistological, ultrastructural and immuno-phenotypical characteristics (CD3-, CIg-, Ki-67- phenotype) of the lymphomatous cells and the cells of the marginal zone were found to be identical, in the dog; this strongly suggests B-lineage cells which do not secrete cytoplasmic immunoglobulins and are not involved in the cell cycle. Finally, these cells seem to us to be morphologically very similar to the minority population described by Van den Oord in the marginal zone of the secondary follicles in the lymph node in humans, in certain reactive situations.

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PubMed1993

IgM and IgA rheumatoid factors in canine polyarthritis.

IgM and IgA rheumatoid factor (RF) were detected by ELISA using a purified dog IgG as antigen in normal controls (N = 84), dogs with unclassified polyarthritis (N = 95), dogs with rheumatoid arthritis (RA) (N = 22), dogs with systemic lupus erythematosus (SLE) (N = 35), dogs with leishmaniasis or heart worm disease (N = 20) and dogs with pyometra (N = 16). Frequency and titre of IgM and IgA RF are low and comparable (P < 0.05) in dogs with unclassified polyarthritis or RA: respectively 24.2% and 27.3% for IgM RF and 21.0% and 18.2% for IgA RF; the mean titre being respectively 0.781 +/- 0.581 and 0.649 +/- 0.365 for IgM RF, and 0.774 +/- 1.331 and 0.740 +/- 1.169 for IgA RF. The frequencies of IgM and IgA RF are a little higher in dogs with SLE (IgM RF: 37.1%, IgA RF: 25.7%) and higher in dogs with leishmaniasis or heart worm disease (45.0% and 30.0%), especially in dogs with pyometra (68.7% and 37.5%). So, although dogs can produce IgM and IgA RF, these auto-antibodies are uncommon in dogs with RA. Furthermore, when RF are present their titre is much lower than in human RA.

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PubMed1992

Canine systemic lupus erythematosus. I: A study of 75 cases.

We studied 75 cases of canine systemic lupus erythematosus (SLE) presenting with at least four criteria of the American Rheumatism Association (ARA), including antinuclear antibodies (ANAb). This disease mainly affects male German shepherds of an average age of 5 years. The most common clinical signs are polyarthritis (91% of cases), and renal (65%) and cutaneo-mucous disorders (60%). Hemolytic anemia is rare (13%). ANAb are present, often at high levels (> 256 up to 10(6) by indirect immunofluorescence on mouse blood smears). The titers are correlated with the severity and the stage of the disease. As double-stranded DNA Ab are rare and as antihistone Ab are frequent, the former could be replaced by the latter in the ARA criteria applied to the SLE dog. Another category of ANAb, named anti-type 1, also seems useful in diagnosing canine SLE. As for therapy, long-term remissions (up to 9 years without treatment) were obtained in 55.6% of 27 SLE dogs treated by levamisole. At first, levamisole was associated with induction corticotherapy, then administered alone and finally discontinued. Side effects were uncommon and transient.

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PubMed1992

Canine systemic lupus erythematosus. II: Antinuclear antibodies.

The frequency and the specificities of antinuclear antibodies (ANAb) were studied in dogs with systemic lupus erythematosus (SLE) and compared to those found in normal dogs and in dogs with various infectious diseases. Whole ANAb were detected by immunofluorescence. Anti-double-stranded DNA Ab were found in only 2% of SLE dogs, whereas anti-single-stranded DNA Ab were present in 21.4% of SLE dogs and in 26.8% of dogs with infectious disease. Antihistone Ab were frequently observed in SLE dogs (71%) and are essentially directed against trypsin-resistant epitopes of H3, H4 and H2A. The Western blots of nuclear extracts of HeLa cells were recognized mainly by type 1 Ab (30%, reacting with bands of 43, 36, 35, 34, 30 and 27 kDa) and by anti-Sm Ab (12%) associated with anti-RNP Ab. Anti-SSA and anti-SSB Ab were rare.

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PubMed1990

Systemic lupus erythematosus in dogs: association to the major histocompatibility complex class I antigen DLA-A7.

The DLA-A,B antigens and the allotypes of the fourth complement component have been determined in German shepherd dogs suffering from systemic lupus erythematosus. We have typed 26 unrelated affected dogs, 11 animals of a three generation family, and 16 dogs of a colony with a high frequency of the disease. The results obtained from the 26 unrelated diseased dogs were compared to those determined in the 23 unaffected German shepherds. The antigen DLA-A7 was found to be predominant in the diseased group with a c2 = 11.02, Pc = 0.02, and a relative risk for the carriers of 11.93. The antigens DLA-A1 and DLA-B5 were negatively associated to the disease (c2 = 14.95, Pc = 0.001, and c2 = 17.16, P = 0.0008 respectively) and thus may be of protective nature. These data were further substantiated by the typing of the three generation family and the colony.

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PubMed1988

Spontaneous familial systemic lupus erythematosus in a canine breeding colony.

A colony of German shepherd dogs was studied in which a high proportion of antinuclear antibody (ANAb) carriers and dogs with systemic lupus erythematosus (SLE)-like signs were found. The titre of serum thymulin and the percentage of circulating T lymphocytes were both low. The incidence of disease decreased down the generations through the introduction of outside sires, thus suggesting a genetic origin for the disease.

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PubMed1988

Systemic lupus erythematosus in a colony of dogs.

A colony of dogs was obtained by the mating of a female German Shepherd Dog crossbred and a male Belgian Shepherd Dog crossbred, both with systemic lupus erythematosus (SLE). The colony also contained 16 dogs representing F1, F2, and F3 generations. Ten colony dogs had circulating antinuclear antibodies, and 5 of the 10 had clinical signs of SLE. Two F3-generation females had signs of severe SLE. Two dogs had antibodies to extractable nuclear antigen, notably 1 dog had antibodies to Smith (Sm) antigen and 1 had antibodies to Sjogren syndrome A (SSA) antigen. Thymulin (serum thymic factor associated with zinc) titers were generally low in the descendants, but fluctuations were detected within the same dog. In vitro response of lymphocytes from these colony dogs to concanavalin A was maximal for lower mitogenic concentrations, compared with response of lymphocytes from 10 healthy dogs. The suppressive lymphocyte activity in 6 autoimmune colony dogs was diminished in comparison with the activity in 5 nonautoimmune colony dogs and 6 healthy dogs.

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PubMed1988

Anti-histone antibodies (ELISA and immunoblot) in canine lupus erythematosus.

In the canine systemic lupus erythematosus (SLE), anti-double stranded DNA (ds-DNA) antibodies (enzyme linked immunosorbent assay (ELISA) or indirect immunofluorescence on Crithidia luciliae) are rare whereas anti-histone antibodies are often found: 61.7% with ELISA and 74% with immunoblot. In canine SLE the pattern of anti-histone antibodies on immunoblot is different from anti-histone antibodies in human SLE. Indeed, histone fractions which are most often recognized by the canine antibodies are by order of frequency H3, H4 and H2A, whereas in man this order is H1, H2B then H3. In the diagnostic criteria of canine SLE, we suggest replacing the anti-ds-DNA antibodies by the anti-histone antibodies detected by immunoblot.

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PubMed1984

Specificities of antinuclear antibodies detected in dogs with systemic lupus erythematosus.

Five hundred and eighty dogs with at least one clinical sign compatible with a systemic lupus erythematosus (SLE) were entered in a prospective study aimed at evaluating the prevalence of antinuclear antibodies (ANAb). SLE was diagnosed in 38 of these dogs (group A) which fulfilled at least four American Rheumatism Association (ARA) criteria; of these, sixteen had ANAb titers greater than or equal to 4096. The 23 dogs which met three or two ARA criteria (group B) had an ANAb geometric mean titer (GMT) of 259. Dogs (group C) with only 1 criterium had an ANAb GMT of 75. Anti-ds-DNA Ab were present in 6 dogs from group A (16%), and 2 dogs from group B (9%). Anti-histone Ab were present among dogs from group A, B and C with frequencies of 81%, 67% and 26%, respectively. Among dogs from group A, the ANAb titers and the levels of anti-histone Ab correlated positively when individual sera were considered. Antibodies against the soluble nuclear antigen (SNA) were detected in 74%, 39% and 13% of the dogs from groups A, B and C, respectively. Antibodies initially described in human SLE also exist in SLE dogs. Anti-Sm Ab were found in 24% of dogs in group A. With anti-RNP Ab the frequency was still lower (10%). However, two other types of anti-SNA Ab against RNAse and trypsin-resistant antigens, not found in human "reference sera", were often detected. The first type (anti-type 1 Ab) was found in 26% and 9% of group A and group B, The first type (anti-type 1 Ab) was found in 26% and 9% of group A and group B, respectively; the second type (anti-type 2 Ab) is less frequent, and was found in 13% and 17% of group A and B, respectively. It appears that testing for anti-Sm, anti-type 1 and anti-histone Ab should be performed in order to improve the diagnosis of SLE in dogs.

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