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Biomedical subjects

M Tulliez

Publications and source records attributed to M Tulliez.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of octreotide treatment on early TNF-alpha production and localization in experimental chronic colitis.

BACKGROUND: Colitis induced by trinitrobenzene sulphonic acid (TNB) is a model of Th1 disease, mainly explored from the third day of induction. It has recently been shown that octreotide and other somatostatin analogues can modify inflammatory/immune processes by acting on cytokines. AIM: To examine TNFalpha production and the effect of preventive treatment with octreotide, during the early phase of TNB-colitis. METHODS: Thirty milligrams TNB with 50% ethanol was instilled into the colon of male Wistar rats. Treated groups received octreotide (2x10 microg x day/rat) or dexamethasone (1x2 mg x day/kg), subcutaneously, with the first injection before TNB. Eight and 80 h later, the colon was excised and processed for histology, TNFalpha immunohistochemistry, quantification of cytokine release ex vivo and tissue-inducible NO synthase (iNOS) activity. RESULTS: Maximal TNFalpha production was observed at the 8th hour, associated with intense immunostaining of the external muscle layer. Octreotide treatment decreased TNFalpha expression (staining and activity) and iNOS activity. At the 80th hour, submucosal macrophages were positive for TNFalpha and colonic production of IL1beta and interferon gamma was increased; all these effects were reduced by octreotide treatment. CONCLUSIONS: TNFalpha was expressed early by resident muscle cells, before staining of infiltrated immune cells and increased production of interferon gamma. TNFalpha regulation by octreotide suggests that this drug might exert anti-inflammatory properties via smooth muscle cells.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1999

[Hepatic ischemia and hypophyseal macroadenoma].

We report the first case of recurrent hepatitis secondary to a pituitary macroadenoma in a 55-year old man. Liver ischemia is thought to be the main consequence of episodes of acute adrenal insufficiency. Sudden acute adrenal insufficiency was due to enlargement of the sella content secondary to several microhemorrhages in the macroadenoma.

Acute Disease↗
PubMed1998

Thrombopoietin (TPO) knockout phenotype induced by cross-reactive antibodies against TPO following injection of mice with recombinant adenovirus encoding human TPO.

Adenovirus vectors have emerged as potent agents for gene transfer. Immune response against the vector and the encoded protein is one of the major factors in the transient expression following in vivo gene transfer. A single injection of an adenovirus encoding human thrombopoietin (TPO) into mice induced transient thrombocytosis, followed by a chronic immune thrombocytopenia. Thrombocytopenic mice had anti-human TPO Abs of the IgG2a and IgG1 isotypes. Thrombocytopenic mice sera neutralized more efficiently human than murine TPO, and exhibited no detectable anti-murine TPO Abs. Despite their low affinity for murine TPO, anti-TPO Abs induced a TPO knockout-like phenotype, i.e., low number of marrow megakaryocytes and of all kinds of hemopoietic progenitors. Hybridomas derived from a thrombocytopenic mouse revealed cross-reactivity of all of the secreted anti-TPO Ab isotypes. Mice subjected to myelosuppression after virus injection showed that anti-human TPO of IgG1 and IgG2a isotypes disappeared. Thus, sustained human TPO production was responsible for platelet elevation for at least 5 mo. Compelling results showed that elevated IgG2a/IgG2b ratios are always associated with thrombocytopenia, whereas low ratios are associated with tolerance or normal platelet counts. Finally, we hypothesize that in humans some chronic thrombocytopenia associated with a low TPO plasma level are due to anti-TPO Abs.

Adenoviridae↗
PubMed1998

The first pathogenic mitochondrial methionine tRNA point mutation is discovered in splenic lymphoma.

We describe a novel point mutation in the mitochondrial DNA transfer RNA methionine gene, a G-to-A transition at position 4450, in a patient with a splenic lymphoma with villous lymphocytes. The patient's lymphocytes were remarkable by the presence of large cytoplasmic inclusions demonstrated as abnormal mitochondria by electron microscopy and led to the discovery of the mutation using denaturing gradient gel electrophoresis as a screening procedure. The pathogenic potential of the mutation was clearly established by the following criteria. It was absent in a control population. It involves a nucleotide that is highly conserved along the phylogenetic tree. The mutation was heteroplasmic and, when present in a high proportion, was associated with morphological alterations of the mitochondria, with defects of respiratory chain complexes activities and with a decrease in the mitochondrially encoded cytochrome c oxidase subunit II. Transfer of the mutation in Rho0 cells allowed to demonstrate its association with a severe respiratory chain dysfunction. However, although the pathogenicity of the mutation was clearly demonstrated, its link with the patient disease remained disputable.

Aged↗
PubMed1998

Plasma homocysteine levels related to interactions between folate status and methylenetetrahydrofolate reductase: a study in 52 healthy subjects.

Hyperhomocysteinemia, a risk factor for vascular disease, is related to vitamin B12, vitamin B6, and especially folate deficiency, or to genetic factors such as mutations in methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the remethylation pathway of homocysteine to methionine. Recently, a C677 --> T mutation identified in the MTHFR gene was found to be frequently associated with decreased MTHFR activity and an elevated plasma homocysteine concentration. Since hyperhomocysteinemia seems to be determined by both genetic and environmental factors, we studied the interactions between MTHFR (phenotype and genotype) and folate status, including methyltetrahydrofolate (methylTHF), the product of MTHFR, on the homocysteine concentration in 52 healthy subjects, (28 women and 24 men; mean age, 32.7 years). MTHFR activity seems to be dependent on folate status, as shown by a lower activity in folate-deficient subjects and a return to normal values after supplementation with folic acid, and also by a decreased enzymatic activity on phytohemagglutinin (PHA)-stimulated lymphocytes grown in a folic acid-deficient medium. Conversely, the C677 --> T mutation seems to influence folate metabolism. Subjects who were homozygous for this mutation (+/+) had significantly higher plasma homocysteine and lower plasma folate and total and methylfolate levels in red blood cells (RBCs) than heterozygous (+/-) and normal (-/-) subjects. The ratio of RBC methylfolate to RBC total folate was, respectively, 0.27 in +/+, 0.66 in +/-, and 0.71 in -/-. This mutation seems to have an impact on methylTHF generation. These data illustrate the interactions between nutritional and genetic factors.

Adult↗
PubMed1998

Increase in tumor necrosis factor-alpha production linked to the toxicity of indomethacin for the rat small intestine.

1. The toxic effects of nonsteroidal anti-inflammatory drugs for the lower gastrointestinal tract share certain features with inflammatory processes, suggesting that the release of inflammation cytokines such as TNF-alpha may damage the intestine. 2. Rats received a s.c. injection of indomethacin. Then, jejunum-ileum was taken up for the quantification of ulcerations, production of TNF-alpha, nitrites and PGE2 ex vivo and activity of calcium-independent NO synthase and myeloperoxydase. Activation of NO metabolism and myeloperoxydase were measured as potential effectors of TNF-alpha. 3. Jejunum-ileum from rats having received indomethacin (10 mg kg(-1)) produced TNF-alpha ex vivo. Cytokine production was associated with the onset of macroscopic ulcerations of the small intestine, and preceded nitrite production and tissue activity of myeloperoxidase. 4. Similar intestinal ulcerations and upregulation of TNF-alpha were obtained with flurbiprofen (30 mg kg(-1)), chemically unrelated to indomethacin. 5. TNF-alpha production was proportional to the indomethacin dose (from 3-20 mg kg(-1)) and correlated with the surface area of ulcerations and nitrite production, 24 h after indomethacin administration. 6. Pretreatment of rats with RO 20-1724, a type-IV phosphodiesterase inhibitor which inhibits TNF-alpha synthesis, substantially reduced jejunum-ileum ulcerations, TNF-alpha and nitrite production and tissue enzyme activities. 7. These findings provide evidence that TNF-alpha is increased in indomethacin-induced intestinal ulcerations and support suggestions that TNF-alpha is involved at an early stage of nonsteroidal anti-inflammatory drug toxicity for the small intestine.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1998

Major effects of TPO delivered by a single injection of a recombinant adenovirus on prevention of septicemia and anemia associated with myelosuppression in mice: risk of sustained expression inducing myelofibrosis due to immunosuppression.

Adenoviral vectors may be useful tools to deliver a cytokine in vivo. A single intravenous injection of an adenovirus vector containing the human thrombopoietin (TPO) cDNA (AdRSVhuTPO) was able to induce a thrombocytosis for more than 6 weeks in SCID mice, associated with a megakaryocyte (MK) hyperplasia in different organs. A marrow and spleen fibrosis was observed at 6 weeks. In immunocompetent mice, a single AdRSVhuTPO injection led to a moderate and transient thrombocytosis without myelofibrosis. To evaluate the usefulness of TPO for the prevention of secondary side-effects during an aplastic period, mice were subjected to a myeloablative regimen 7 days after the intravenous AdRSVhuTPO injection. In this setting, TPO prevented mortality by accelerating hematological recovery. Survival was essentially related to an improvement in the leukopenia since all control mice died from septicemia. However, the effects of TPO may be potentiated by the release of inflammatory cytokines following the adenovirus infection; AdRSV beta galactosidase injected-mice had higher numbers of BFU-E and CFU-GM in the marrow than PBS-injected mice. Myelosuppression induced transient immunosuppression responsible for a sustained expression and elevation of platelet numbers for at least 5 months. These results further suggest that TPO may be an effective therapy in diminishing hematological complications related to myeloablative regimens, but emphasize that immunosuppression secondary to myelosuppression may lead to sustained expression associated with a risk of thrombosis and myelofibrosis when delivered by adenovirus vectors.

Adenoviridae↗
PubMed1998

Effects of murine recombinant interleukin-10 on the inflammatory disease of rats transgenic for HLA-B27 and human beta 2-microglobulin.

Rats transgenic for HLA-B27 and human beta 2-microglobulin develop a spontaneous, multisystem, inflammatory disease that resembles human B27-associated disease and that involves the gut mucosa. This model predominantly affects the colon and is characterized by an extensive infiltration of the mucosa by inflammatory cells, largely composed of mononuclear cells. In addition, an increased plasma level of nitric oxide (NO)-derived metabolites was described in this model. Deficiency in the anti-inflammatory cytokine, interleukin-10 (IL-10), leads to the development of colitis in IL-10 knockout mice, suggesting that IL-10 plays a major role in the control of gut inflammation. The objectives of this work were to study the mechanisms of the inflammatory bowel disease (IBD) in HLA-B27 rats and to determine the effects of treatment with IL-10. The 33-3 line of HLA-B27 recombinant rats with established disease was treated in two consecutive experiments with murine recombinant IL-10 for five weeks. Assessment of the effect of this treatment was performed, based on clinical, histological and biological (myeloperoxidase and inducible NO synthase activities; tumor necrosis factor-alpha, interferon-delta, CD3, iNOS and beta-actin mRNA expression. In 33-3 rats with established disease, mesenteric lymph nodes were hyperplastic, and colonic cellularity and MPO and iNOS activities in the colonic mucosa were increased without any detectable effects of IL-10 administration. IFN-gamma and iNOS mRNA were only detected in the colon of transgenic rats. Despite a lack of effect on disease expression, IL-10 strikingly reduced the level of IFN-gamma mRNA in gut mucosa. Up-regulation of IFN-gamma mRNA suggests that the IBD of HLA-B27 rats is mediated by T-helper 1 lymphocytes. Sustained administration of IL-10, in HLA-B27 rats with established disease, efficiently inhibited IFN-gamma mRNA expression but did not influence disease expression: these results indicate that IFN-gamma may exert a critical role at an earlier stage of the disease rather in the maintenance of the lesions.

Animals↗
PubMed1998

[Turner syndrome and nodular regenerative hyperplasia of the liver].

Turner's syndrome is an ovarian dysgenesis (karyotype 45 X0) characterized by sexual infantilism and multiple malformations. Liver enzyme anomalies are often observed, but the underlying pathogenic mechanism remains unknown. Nodular regenerative hyperplasia of the liver is associated with another disease in about 80% of cases. However, these two diseases have only been reported together in one woman. We describe here a second case of this association "Turner's syndrome and nodular regenerative hyperplasia". We think that women with Turner's syndrome should benefit from screening for nodular regenerative hyperplasia by searching for elevated liver enzymes. This easily applicable screening protocol would provide early diagnostic of nodular regenerative hyperplasia and allow early and effective treatment of portal hypertension. Moreover, this approach would improve our knowledge of this association.

Adult↗
PubMed1998

[Castleman's disease and chromophobe carcinoma of the kidney. An incidental association?].

We report a case of Castleman's disease in a 65-year-old female, revealed by a renal tumor associated with inter-aortico-cava adenopathies and renal chromophobe cell carcinoma. This observation points to the difficulties in differentiating local Castleman's disease, which may be cured by surgical excision, from multicentric disease associated with a dysimmune syndrome of uncertain prognosis. The association of multicentric Castleman's disease with a carcinoma has rarely been described. It could be the emergence of a neoplasia in a context of dysimmunity or Castleman's disease might be related to the production of interleukin 6 by a renal carcinoma.

Adenocarcinoma↗
PubMed1997

High thrombopoietin production by hematopoietic cells induces a fatal myeloproliferative syndrome in mice.

To evaluate the effects of long-term, high-dose exposure to thrombopoietin (TPO), lethally irradiated mice were grafted with bone marrow cells infected with a retrovirus carrying the murine TPO cDNA. Mice were studied for 10 months after transplantation. In plasma, TPO levels were highly elevated (10(4) U/mL) throughout the course of the study. All mice developed a lethal myeloproliferative disorder evolving in two successive phases. During the first phase (7-9 weeks posttransplant), platelet and white blood cell (WBC) counts rose four- and ten-fold, respectively, whereas hematocrits decreased slightly to 29% +/- 3%. The WBC were mainly mature granulocytes, but myeloid precursor cells were invariably observed as well as giant platelets with an irregular granule distribution. The striking features were a massive hyperplasia of megakaryocytes and granulocytes in the spleen and bone marrow and a hypoplasia of erythroblasts in bone marrow. Total numbers of megakaryocyte colony-forming cell, burst-forming unit-erythroid, and granulocyte macrophage colony-forming cells were increased but colony-forming unit-erythroid numbers decreased. From 10 weeks posttransplant and thereafter, WBC, platelets, and red blood cell numbers declined dramatically. The absolute numbers of progenitor cells were very low in the spleen and bone marrow, but sharply increased in the blood and peritoneal cavity. Extramedullary hematopoiesis was observed in several organs. Histologic sections of the spleen and bones revealed severe fibrosis and osteosclerosis. The mean survival time was 7 months posttransplant and mice died with severe pancytopenia. Notably, two mice died between 3 and 4 months posttransplant with a leukemic transformation. This disorder was transplantable into secondary recipients who developed an attenuated form of the disease similar to the one previously described (Yan et al, Blood 86:4025, 1995). Taken together, our data show that high and persistent TPO production by transduced hematopoietic cells in mice results in a fatal myeloproliferative disorder that has a number of features in common with human idiopathic myelofibrosis.

Animals↗
PubMed1997

In vivo effects of activated H-ras oncogene expressed in the liver and in urogenital tissues.

Transgenic mouse technology provides a direct genetic approach to in vivo carcinogenesis. In order to determine the oncogenic potential of an activated ras gene in liver, kidney and intestine, we created transgenic mice expressing the human H-ras oncogene under control of the L-type pyruvate-kinase gene. This gene is expressed in hepatocytes, enterocytes, proximal tubular cells of the kidney and endocrine pancreatic cells. Depending on lines, we observed hepatocarcinoma, polycystic kidney disease and an unexpected epididymis hyperplasia. These transgenic mice are an interesting model of polycystic kidney disease, and complete our study of the tissue-specificity of oncogene action.

Animals↗
PubMed1997

Haemophagocytic syndrome in patients infected with the human immunodeficiency virus: nine cases and a review.

We report nine cases of haemophagocytic syndrome (HS) in patients with human immunodeficiency virus infection, and review the 17 cases described to date in the literature. In 21 of 26 cases, HS developed during an advanced stage of immunodeficiency. Clinical and haematological signs are not specific in this setting, and the diagnosis relies on histological features, mainly bone marrow examination. An opportunistic infection was associated in three cases and a lymphoid malignancy in two of our nine cases. The role of the human immunodeficiency virus in the occurrence of the HS remains to be defined. The overall prognosis is poor as six of our nine patients died within 12 months of presentation.

Adult↗
PubMed1997

A new c-kit mutation in a case of aggressive mast cell disease.

Systemic mast cell disease (SMCD) is a disorder characterized by a mast cell proliferation in various tissues. Mast cells express the c-kit proto-oncogene. A few cases of c-kit mutations have been described in SMCD. We report an aggressive SMCD in a patient who presented with a bone marrow infiltration by abnormal mast cells. Molecular studies of mast cell DNA and RNA revealed a new c-kit heterozygous mutation (Asp820Gly). This mutation leads to a drastic amino-acid change and is located close to the highly oncogenic Asp816Val. These findings suggest that the Asp820Gly has a potential role in c-kit activation.

Adult↗
PubMed1997

Role of hemophagocytic histiocytosis in the etiology of thrombocytopenia in patients with sepsis syndrome or septic shock.

We conducted a study to assess the incidence and outcome of hemophagocytic histiocytosis (HH) in thrombocytopenic patients with sepsis syndrome or septic shock and to define the possible associations between HH, disseminated intravascular coagulation (DIC), and platelet-associated IgG (PAIgG) in promoting thrombocytopenia. Twenty immunocompetent thrombocytopenic patients were included. Bone marrow aspirates were obtained from each patient to identify hemophagocytic histiocytes. Coagulation parameters, PAIgG levels, and bacterial and viral infections were studied. Twelve patients with HH were identified. The presence of DIC and of PAIgG were often associated with this disease. No herpesvirus infection was demonstrated. Eight of the 12 patients with HH and four of the eight patients without HH died (P = NS). The results of this study suggest that HH could be involved in the development of thrombocytopenia in immunocompetent patients with sepsis syndrome or septic shock. HH does not seem to be associated with increased mortality.

Aged↗
PubMed1997

Direct ex vivo simian immunodeficiency virus (SIV)-specific cytotoxic activity detected from small intestine intraepithelial lymphocytes of SIV-infected macaques at an advanced stage of infection.

Human immunodeficiency virus (HIV) induces a profound disorganization of the lymphoid tissues with marked abnormalities of the immune system at the terminal stage of infection. Since the digestive mucosal immune system is by far the largest lymphoid organ of the body, we attempted to evaluate its functional activity in advanced stages of simian immunodeficiency virus (SIV) infection in the SIV-macaque model of HIV infection. Two chronically intravenously SIV-infected macaques, including one at the AIDS stage, were studied. Intestinal intraepithelial lymphocytes (IEL) were isolated, analyzed, and compared to lymphocytes obtained from blood, spleen, and different lymph nodes: IEL were predominantly CD8+ T lymphocytes expressing the alphaE beta7 integrin and lacking the CD28 coactivatory molecule. A direct ex vivo SIV-specific cytotoxic activity was prominently found in the IEL of both macaques and was weaker or absent in the other sites. To our knowledge, this is the first report of SIV-specific cytotoxic activity from small intestine IEL in SIV-infected macaques. Considering the high similitude of the SIV-macaque model with the HIV infection in humans, these results may be highly important for the pathogenesis of HIV infection and more generally important for the characterization and function of digestive CD8+ IEL population.

Animals↗
PubMed1997

[Hepatic distomatosis of tumor form after prolonged treatment with corticoids].

A 49-year woman, living in Cameroun and treated by steroids for connective tissue disease, was admitted for a liver mass and epigastric pain. An increase in blood count of eosinophils (1,590.10(9)/L) was observed. Imaging examination showed the presence of a voluminous, multilocular, and heterogeneous hepatic lesion. Pathological examination of the liver showed no evidence of tumor but revealed a rounded cuticle remnant, compatible with bilharziosis eggs or loase transversal section, and Charcot-Leyden's crystals. Due to the uncertainty of diagnosis, a right hepatectomy was performed. Pathological and parasitological examination of the surgical specimen confirmed the diagnosis of hepatic distomatosis, with typical eggs of Fasciola hepatica within necrotic tissue, surrounded by eosinophilic inflammatory infiltrates. Specific serology was positive. The presence of intraparenchymatous eggs was unusual and reflected the ectopic migration of a mature fluke into the hepatic parenchyma, even though the worm was not found in the surgical specimen. Serology for fascioliasis should be performed in any patient suffering from hepatic lesions with eosinophilia.

Diagnosis, Differential↗